Duchenne Muscular DystrophyPhase 2NCT02907619
An Open-label Extension Study To Evaluate Safety Of PF-06252616 In Boys With Duchenne Muscular Dystrophy
A Phase 2 study testing PF-06252616 in people with Duchenne Muscular Dystrophy, run by Pfizer at 47 sites in 5 countries.
Trial summary
This study is an open-label extension to protocol B5161002 and will provide an assessment of the long term safety, efficacy, pharmacodynamics and pharmacokinetics of intravenous dosing of PF 06252616 in boys with Duchenne muscular dystrophy. Read more about this study
- Who is it for?
- Ages 6 to 18 years, men only
- Conditions the study is for
- Duchenne Muscular Dystrophy
- What is being tested?
- PF-06252616
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 59 participants
- Where
- 47 sitesin 5 countries
- Study dates
- 13 Oct 2016to 22 Nov 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 18 years
- Men only
- No healthy volunteers
- Child, Adult
Who may be able to join
- Subjects with Duchenne muscular dystrophy who enrolled and completed study B5161002.
- Signed and dated informed consent document (ICD) indicating that the subject's parent or legal guardian/caregiver has been informed of all pertinent aspects of the study.
- Subjects and their legal guardians/caregivers who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
- Subject have;
- Adequate hepatic function on screening laboratory assessments
- GLDH less than 20 units/liter (2 x upper limit of normal [ULN])
- Iron content estimate on the liver MRI within the normal range.
Who cannot join
- Unwilling or unable (eg, metal implants) to undergo examination with closed MRI.
- All male subjects who are able to father children and are sexually active and at risk for impregnating a female partner, who are unwilling or unable to use a highly effective method of contraception. In addition, all sexually active male subjects who are unwilling or unable to prevent potential transfer of and exposure to drug through semen to their partners by using a condom consistently and correctly. .
- Subjects who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, or subjects who are related to Pfizer employees directly involved in the conduct of the study.
- Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation.
- Participation in other studies involving investigational drug(s), with the exception of B5161002.
- History of allergic or anaphylactic reaction to a therapeutic or diagnostic protein or additives of this investigational product.
Trial locations and contacts
47 sites in 5 countries.
47 sites in 5 countries
United States26 sites
Kennedy Krieger Institute Out-patient Center
Baltimore, Maryland, 21205
Kennedy Krieger Institute
Baltimore, Maryland, 21205
Johns Hopkins Hospital
Baltimore, Maryland, 21287
Johns Hopkins Investigational Drug Service
Baltimore, Maryland, 21287
Massachusetts General Hospital
Boston, Massachusetts, 02114
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Duke University Medical Center, Lenox Baker Children's Hospital
Durham, North Carolina, 27705
Duke University, Investigational Drug Pharmacy
Durham, North Carolina, 27710
University of Iowa ICTS, Clinical Research Unit
Iowa City, Iowa, 52242
David Geffen School of Medicine at UCLA/UCLA Neurology
Los Angeles, California, 90095
Ronald Reagan UCLA Medical Center
Los Angeles, California, 90095
Ronald Reagan UCLA Pharmacy
Los Angeles, California, 90095
UCLA (David Geffen School of Medicine), Department of Orthopedic Surgery
Los Angeles, California, 90095
UCLA Clinical & Translational Research Center
Los Angeles, California, 90095
University of Minnesota Masonic Children's Hospital
Minneapolis, Minnesota, 55454
(For Drug deliveries) IDS Pharmacy
Minneapolis, Minnesota, 55455
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
University of California, Davis Medical Center
Sacramento, California, 95817
Center for Clinical and Translational Sciences
Salt Lake City, Utah, 84108
Utah Center for Advanced Imaging and Research (UCAIR)
Salt Lake City, Utah, 84108
Investigational Drug Services
Salt Lake City, Utah, 84112
Utah Program for Inherited Neuromuscular Disorder
Salt Lake City, Utah, 84112
University of Utah Hospital
Salt Lake City, Utah, 84132
University of Utah School of Medicine
Salt Lake City, Utah, 84132
St. Louis Childrens's Hospital
St Louis, Missouri, 63110
Italy9 sites
UOC Farmacia - Istituto Gianna Gaslini,
Genova, 16147
UOC Medicina Fisica Riabilitativa - Istituto G. Gaslini
Genova, 16147
UOC Neurologia Pediatrica e Malattie Muscolari Istituto Gianna Gaslini
Genova, 16147
UOC Radiologia - Istituto Gianna Gaslini,
Genova, 16147
UOS Dipartimentale Endocrinologia Clinica Sperimentale - Ist.
Genova, 16147
Dipartimento Pediatrico Universitario-Ospedaliero Endocrinologia
Rome, 00150
Farmacia Ospedaliera, IRCCS Ospedale Pediatrico Bambino Gesu
Rome, 00165
IRCCS Ospedale Pediatrico Bambino Gesu - Centro Trials
Rome, 00165
U.O. Malattie Neuromuscolari e Neurodegenerative, IRCCS Ospedale Pediatrico Bambino Gesu
Rome, 00165
Canada5 sites
Alberta Children's Hospital
Calgary, Alberta, T3B 6A8
Children's Hospital- London Health Sciences Centre
London, Ontario, N6A5W9
Centre de Readaptation Marie Enfant (CRME)
Montreal, Quebec, H1T 1C9
CHU Sainte-Justine
Montreal, Quebec, H3T 1C5
UBC Children's and Women's Health Centre of British Columbia
Vancouver, British Columbia, V6H 3V4
United Kingdom5 sites
Dubowitz Neuromuscular Centre, Institute of Child Health
London, WC1N 3JH
Great Ormond Street Hospital
London, WC1N 3JH
Institute of Genetic Medicine,Muscle Team
Newcastle upon Tyne, NE1 3BZ
Clinical Research Facility
Newcastle upon Tyne, NE1 4LP
Royal Victoria Infirmary Research Pharmacy
Newcastle upon Tyne, NE1 4LP
Japan2 sites
National Center of Neurology and Psychiatry
Kodaira, Tokyo, 187-8551
Hyogo college of medicine hospital
Nishinomiya-shi, Hyōgo, 663-8501
About this study
Official title: A MULTICENTER, OPEN-LABEL EXTENSION STUDY TO EVALUATE THE LONG TERM SAFETY OF PF-06252616 IN BOYS WITH DUCHENNE MUSCULAR DYSTROPHY
This study is an open-label extension to protocol B5161002 and will provide an assessment of the long term safety, efficacy, pharmacodynamics and pharmacokinetics of intravenous dosing of PF 06252616 in boys with Duchenne muscular dystrophy. Approximately 105 eligible subjects will be assigned to receive a monthly individualized maximum tolerated dose based on their tolerability profile/data from B5161002. This study will not contain a placebo comparator. Subjects will undergo safety evaluations (Laboratory, cardiac monitoring, physical exams, x-ray, MRI), functional capacity evaluations (4 stair climb, range of motion, strength testing, Northstar Ambulatory Assessment, upper limb functional testing, six minute walk test and pulmonary function tests) and pharmacokinetic testing.
- Conditions
- Duchenne Muscular Dystrophy
- Being tested
- PF-06252616
- Keywords
- Duchenne muscular dystrophy, myostatin, open-label
- Medical subject headings
- Muscular Dystrophy, Duchenne
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PF-06252616Biological
Either 5mg/kg, 20mg/kg or 40mg/kg will be assigned to a subject based on their maximum tolerated dose from B5161002
| Study group | Role | What they receive |
|---|---|---|
| PF-06252616 | Experimental | Either 5mg/kg, 20mg/kg or 40mg/kg will be assigned to a subject based on their maximum tolerated dose from B5161002 Receives: Biological: PF-06252616 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Dose Reduced or Temporary Discontinuation Due to AEs
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment or usage. Treatment-related AEs were determined by the investigator. The number of participants with dose reduced or temporary discontinuation due to both all-causality and treatment-related AEs are presented below.
Measured: 2 Years
Number of Participants With Severe Treatment-Emergent Adverse Events (TEAEs)
An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment or usage. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment. Severe TEAEs were TEAEs that interfered significantly with participants' usual function. Treatment-related TEAEs were determined by the investigator. The number of participants with severe all-causality and treatment-related TEAEs are presented below.
Measured: 2 Years
Number of Participants Who Discontinued From the Study Due to TEAEs
An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment or usage. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment. Treatment-related TEAEs were determined by the investigator. The number of participants who discontinued from the study due to both all-causality and treatment-related TEAEs are presented below.
Measured: 2 Years
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hematology
Hematology evaluation included: hemoglobin, hematocrit, red blood cell (RBC) count, platelets, RBC morphology, white blood cell (WBC) count, absolute lymphocytes, absolute atypical lymphocytes, absolute total neutrophils, absolute total neutrophils count, absolute band cells, absolute basophils, absolute eosinophils and absolute monocytes.
Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004.
(ULN=Upper Limit of Normal; LLN=Lower Limit of Normal).
Measured: 2 Years
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Coagulation
Coagulation evaluation included activated partial thromboplastin time (aPTT) and prothrombin time (PT).
(ULN=Upper Limit of Normal). Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004.
Measured: 2 Years
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Liver Function
Liver function evaluation included: total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), alkaline phosphatase, total protein, albumin and glutamate dehydrogenase.
Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004.
(LLN=Lower Limit of Normal; ULN=Upper Limit of Normal).
Measured: 2 Years
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Renal Function
Renal function evaluation included: blood urea nitrogen (BUN), creatinine and uric acid.
Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. (ULN=Upper Limit of Normal).
Measured: 2 Years
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Electrolytes
Electrolytes evaluation included: sodium, potassium, chloride, calcium, phosphate and bicarbonate.
Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004.
(LLN=Lower Limit of Normal, ULN=Upper Limit of Normal).
Measured: 2 Years
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hormones
Hormone evaluations included free thyroxine (T4), thyroid stimulating hormone (TSH), lutenizing hormone (LH), follicle stimulating hormone (FSH), and androstenedione. Numbers of participants with abnormalities of LH, FSH and androstenedione were reported in different age groups.
Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004.
(LLN=Lower Limit of Normal, ULN=Upper Limit of Normal).
Measured: 2 Years
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Clinical Chemistry
Clinical chemistry evaluation included glucose, creatine kinase (CK), troponin I, amylase, iron binding capacity, unsaturated iron binding capacity, transferrin saturation, iron and ferritin. Number of participants with iron abnormalities was reported in different age groups.
Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004.
(LLN=Lower Limit of Normal, ULN=Upper Limit of Normal).
Measured: 2 Years
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Urinalysis
Urinalysis Microscopy included: urine red blood cell (RBC), urine white blood cell (WBC), urine uric acid crystals, urine calcium oxalate crystals, urine amorphous crystals, urine bacteria, urine microscopic exam.
Urinalysis Dipstick included: urine pH, urine glucose, urine ketones, urine protein, urine blood/hemoglobin, urine nitrite, urine leukocyte esterase.
Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004.
Measured: 2 Years
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Fecal Blood
Number of participants with blood detected in fecal samples is presented. Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004.
(ULN=Upper Limit of Normal).
Measured: 2 Years
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline
Participants were asked to fast for at least 8 hours prior to collection of blood to evaluate serum iron, serum ferritin and % transferrin saturation. The unit of iron was mcg/dL; the unit of ferritin was ng/mL; the unit of %transferrin saturation was %.
Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.
Measured: Baseline, Weeks 13, 25, 37, 49, 61, 73 and 85.
Number of Participants With Significant Results of Physical Examinations Including Nose and Throat Mucosal Examinations
Physical examinations were conducted by a physician, trained physician's assistant, or nurse practitioner as acceptable according to local regulation. A targeted nose and throat mucosal exam was performed to monitor for any signs of mucosal telangiectasias. The clinically significant physical examination results were determined by the investigator.
Measured: 2 Years
Summary of Pubertal Development by Tanner Stage
Tanner staging was performed before the first dose of this study to monitor for signs of accelerated sexual development. The physical changes in pubertal development (pubic hair, penis and testes) were assessed using the system described by Marshall and Tanner. Stage 1 is preadolescent, Stages 2, 3, and 4 are initiation of puberty and Stage 5 is mature adult. Details about the system can be referred to Tanner JM. Growth at Adolescence. Blackwell Scientific Publications 1962; 2nd edition.
Participant's Week 97 visit within study B5161002 (parent study) was collected as screening data.
Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.
Measured: Screening, Baseline, Week 49.
Summary of Testicular Volume
Testicular volume was used to monitor pubertal development. Participant's Week 97 visit within Study B5161002 (parent study) was collected as screening data in current study.
Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.
Measured: Screening, Baseline, Week 49.
Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria - B5161004 Baseline
The number of participants pre-dose supine blood pressure and pulse rate meeting categorical summarization criteria are recorded in this table.
Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004.
(DBP=diastolic blood pressure, SBP=systolic blood pressure; The unit for blood pressure is: mmHg, the unit for pulse rate is: beats per minute [BPM])
Measured: 2 Years
Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria - Overall Baseline
The number of participants with data of pre-dose supine blood pressure meeting categorical summarization were recorded in this table.
Overall Baseline was defined as the last pre-dose assessment prior to the first day of dosing in study B5161002.
(DBP=diastolic blood pressure, SBP=systolic blood pressure; The unit for blood pressure is: mmHg).
Measured: 2 Years
Number of Participants With Post-Baseline ECG Data Meeting Categorical Summarization Criteria - B5161004 Baseline
QTcF=QT/(60/Hour)**(1/3). Means of replicates were used in the calculations. QT=time between the start of the Q wave and the end of the T wave in the heart's electrical cycle; QTcF=corrected QT (Fridericia correction). All scheduled ECGs were performed after the participant had rested quietly for at least 10 minutes in a supine position.
Baseline was defined as the average of the last triplicate pre-dose measurements prior to Day 1 in B5161004.
Measured: 2 Years
Number of Participants With Post-Baseline ECG Data Meeting Categorical Summarization Criteria - Overall Baseline
QT=time between the start of the Q wave and the end of the T wave in the heart's electrical cycle; QTcF=corrected QT (Fridericia correction). All scheduled ECGs were performed after the participant had rested quietly for at least 10 minutes in a supine position.
Overall baseline was defined as the average of the last triplicate pre-dose measurements prior to the first day of dosing in study B5161002.
Measured: 2 Years
Number of Participants With Iron Accumulation Data Meeting Categorical Summarization Criteria
Liver Magnetic Resonance Imaging (MRIs) were sent to an independent central radiology imaging facility for calculation of the average R2* value which was used to monitor for iron accumulation in the liver. Mean R2* values had been used in the calculations.
Normal: R2* <= 75 Hz at 1.5 T or <=139 Hz at 3.0 T; Above Normal: R2* > 75 Hz and <= 190 Hz at 1.5 T or R2* > 139 Hz and <= 369 Hz at 3.0 T Mild overload: R2* > 190 Hz at 1.5 T or R2* > 369 Hz at 3.0 T Data from participant's Week 93 visit in Study B5161002 (parent study) were used for screening in the current study.
Measured: Screening and Week 49.
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) by Cardiac MRI - B5161004 Baseline
The LVEF was the ratio of blood ejected during systole to blood in the ventricle at the end of diastole. LVEF was measured by cardiac magnetic resonance imaging (MRI) or echocardiography. The same method of cardiac imaging was used consistently for each participant. Cardiac MRIs were read by a central imaging vendor, while echocardiograms were read locally (at each site). The table presents the results from cardiac MRIs. Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.
Measured: Baseline and Week 49.
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) by Cardiac MRI - Overall Baseline
The LVEF was the ratio of blood ejected during systole to blood in the ventricle at the end of diastole. LVEF was measured by cardiac magnetic resonance imaging (MRI) or echocardiography. The same method of cardiac imaging was used consistently for each participant. Cardiac MRIs were read by a central imaging vendor, while echocardiograms were read locally (at each site). The table presents the results from cardiac MRIs.
Overall baseline was defined as the last pre-dose assessment prior to the first day of dosing in study B5161002. Week 1 was counted starting from the study treatment in study B5161002.
Measured: Baseline, Weeks 49, 97, 146.
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) by Echocardiogram - B5161004 Baseline
The LVEF was the ratio of blood ejected during systole to blood in the ventricle at the end of diastole. LVEF was measured by cardiac magnetic resonance imaging (MRI) or echocardiography. The same method of cardiac imaging was used consistently for each participant. Cardiac MRIs were read by a central imaging vendor, while echocardiograms were read locally (at each site). The table presents the results from echocardiograms.
Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.
Measured: Baseline, Week 49.
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) by Echocardiogram - Overall Baseline
The LVEF was the ratio of blood ejected during systole to blood in the ventricle at the end of diastole. LVEF was measured by cardiac magnetic resonance imaging (MRI) or echocardiography. The same method of cardiac imaging was used consistently for each participant. Cardiac MRIs were read by a central imaging vendor, while echocardiograms were read locally (at each site). The table presents the results from echocardiograms.
Overall baseline was defined as the last pre-dose assessment prior to the first day of dosing in study B5161002. Week 1 was counted starting from the study treatment in study B5161002.
Measured: Baseline, Weeks 49, 97, 146.
Bone Age to Chronological Age Ratio
Bone age assessment was evaluated by the ratio of the bone age to the chronological age using the X rays of the hand and wrist. Ratio of bone age to chronological age was calculated by bone age/chronological age at scan date. Chronological age at scan date was calculated by (scan date - date of birth + 1)/365.25.
Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.
Measured: Baseline and Week 49.
Whole Body and Spine DXA: Bone Mineral Density Z-Score, Height Adjusted Over Time
Bone mineral density (BMD) was monitored by dual energy x-ray absorptiometry (DXA). DXA scans were obtained to evaluate bone mineral density of the spine and whole body without head.
The height adjusted Z-score presented below is the number of standard deviations which compares the BMD of the participant to the average BMD matched for their age, sex and ethnicity. If the Z-score was -2 standard deviations or lower, the result was "below the expected range for age". If the Z-score was above -2 standard deviations, the result was "within the expected range for age".
Measured: Screening (Week 97 visit within parent study B5161002) and Week 49
Number of Participants With Suicidal Ideation or Suicidal Behavior
The Columbia Suicide Severity Rating Scale (C-SSRS) was performed to identify the risk of suicide ideation or behavior. C-SSRS was conducted with the participant's caregiver/legal guardian on the participant's behalf throughout the study, rather than administering this evaluation directly with the study participants. If at any visit the participant endorsed a 4 or 5 on the C-SSRS ideation section or reported any suicidality behavior, then an evaluation of suicide risk (risk assessment) had to be completed and the participant must have been discontinued. The significant result of C-SSRS was determined by the investigator.
Measured: 2 Years
Secondary outcomes (22)
Change From Baseline on the 4 Stair Climb (4SC) - B5161004 Baseline
The 4SC quantified the time required for a participant to ascend 4 standard steps. The functional assessment of 4SC was conducted by a physiotherapist (or exercise physiologist). In order to provide optimal testing conditions and consistency in endpoint measurements, the functional assessments were completed at approximately the same time of day.
Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.
Measured: Baseline, Weeks 13, 25, 49, 73.
Change From Baseline on the 4SC - Overall Baseline
The 4SC quantified the time required for a participant to ascend 4 standard steps. The functional assessment of 4SC was conducted by a physiotherapist (or exercise physiologist). In order to provide optimal testing conditions and consistency in endpoint measurements, the functional assessments were completed at approximately the same time of day.
This is the overall change from baseline which included the change since enrolling in the parent study B5161002.
Overall baseline was defined as the last pre-dose assessment prior to the first day of dosing in study B5161002. Week 1 was counted starting from the study treatment in study B5161002.
Measured: Baseline, Weeks 9,17,25,33,41,49,57,65,73,81,89,97,110,122,146,170.
Change From Baseline on the Forced Vital Capacity (FVC) - B5161004 Baseline
FVC was measured using the FVC maneuver by spirometry to evaluate respiratory muscle function. The best (largest) FVC measurement from a set of 3 was captured on the database.
Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.
Measured: Baseline, Weeks 13, 25, 49 and 73.
Change From Baseline on the FVC - Overall Baseline
Forced vital capacity (FVC) was measured using the FVC maneuver by spirometry to evaluate respiratory muscle function. The best (largest) FVC measurement from a set of 3 was captured on the database. This is the overall change from baseline which included the change since enrolling in the parent study B5161002.
Overall baseline was defined as the last pre-dose assessment prior to the first day of dosing in study B5161002. Week 1 was counted starting from the study treatment in study B5161002.
Measured: Baseline, Weeks 9,17,25,33,41,49,57,65,73,81,89,97,110,122,146,170.
Change From Baseline on the Northstar Ambulatory Assessment (NSAA) Score - B5161004 Baseline
The NSAA was a 17-item test that measured gross motor function. Each individual item was evaluated with either 0-unable to perform independently, 1-able to perform with assistance, 2-able to perform without assistance. A total score was achieved by summing all the individual items. The total score could range from 0 to 34 (fully-independent function).
Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.
Measured: Baseline, Weeks 13, 25, 49, 73.
Change From Baseline on the NSAA Score - Overall Baseline
The NSAA was a 17-item test that measured gross motor function. Each individual item was evaluated with either 0-unable to perform independently, 1-able to perform with assistance, 2-able to perform without assistance. A total score was achieved by summing all the individual items. The total score could range from 0 to 34 (fully-independent function). This is the overall change from baseline which included the change since enrolling in the parent study B5161002.
Overall baseline was defined as the last pre-dose assessment prior to the first day of dosing in study B5161002. Week 1 was counted starting from the study treatment in study B5161002.
Measured: Baseline, Weeks 9,17,25,33,41,49,57,65,73,81,89,97,110,122,146,170.
Change From Baseline on the NSAA - Time to Stand From Supine - B5161004 Baseline
Rise from supine was a timed functional test within NSAA. This test of time-to-stand from supine was analyzed separately for summary tabulation along with the total NSAA score.
Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.
Measured: Baseline, Weeks 13, 25, 49, 73.
Change From Baseline on the NSAA - Time to Stand From Supine - Overall Baseline
Rise from supine was a timed functional test within NSAA. This test of time-to-stand from supine was analyzed separately for summary tabulation along with the total NSAA score. This is the overall change from baseline which included the change since enrolling in the parent study B5161002.
Overall baseline was defined as the last pre-dose assessment prior to the first day of dosing in study B5161002. Week 1 was counted starting from the study treatment in study B5161002.
Measured: Baseline, Weeks 9,17,25,33,41,49,57,65,73,81,89,97,110,122,146,170.
Change From Baseline on the NSAA - Time to Complete 10 m Run/Walk - B5161004 Baseline
A time to event analysis was performed for loss of ambulation. Loss of ambulation was defined as the inability to walk unassisted and without braces for at least 10 m, as assessed and reported by the investigator at each study visit, and confirmed by the inability to walk/run 10 m (as 1 component of the NSAA) evaluated at the next visit at which timed function tests were performed.
Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.
Measured: Baseline, Weeks 13, 25, 49, 73.
Change From Baseline on the NSAA - Time to Complete 10 m Run/Walk - Overall Baseline
A time to event analysis was performed for loss of ambulation. Loss of ambulation was defined as the inability to walk unassisted and without braces for at least 10 m, as assessed and reported by the investigator at each study visit, and confirmed by the inability to walk/run 10 m (as 1 component of the NSAA) evaluated at the next visit at which timed function tests were performed. This is the overall change from baseline which included the change since enrolling in the parent study B5161002.
Overall baseline was defined as the last pre-dose assessment prior to the first day of dosing in study B5161002. Week 1 was counted starting from the study treatment in study B5161002.
Measured: Baseline, Weeks 9,17,25,33,41,49,57,65,73,81,89,97,110,122,146,170.
Change From Baseline on the Ankle Range of Motion (ROM) - B5161004 Baseline
ROM of the ankle was evaluated by goniometry and any occurrences of ankle contractures were recorded. In order to provide optimal testing conditions and consistency in endpoint measurements, the functional assessment of ankle ROM was completed at approximately the same time of day.
Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.
Measured: Baseline, Weeks 13, 25, 49 and 73.
Change From Baseline on the Ankle ROM - Overall Baseline
ROM of the ankle was evaluated by goniometry and any occurrences of ankle contractures were recorded. In order to provide optimal testing conditions and consistency in endpoint measurements, the functional assessment of ankle ROM was completed at approximately the same time of day. This is the overall change from baseline which included the change since enrolling in the parent study B5161002.
Overall baseline was defined as the last pre-dose assessment prior to the first day of dosing in study B5161002. Week 1 was counted starting from the study treatment in study B5161002.
Measured: Baseline, Weeks 9,17,25,33,41,49,57,65,73,81,89,97,110,122,146,170.
Change From Baseline on the Performance of Upper Limb (PUL) Overall Score - B5161004 Baseline
The PUL scale was used to assess motor performance of the upper limb for individuals with DMD. The PUL scale includes 22 items; an entry item defining the starting functional level, and 21 items subdivided into 3 levels; shoulder (4 items), middle (9 items) and distal (8 items). Scoring options per item may not be uniform and may vary from 0-1 to 0-6, according to the performance, with higher values corresponding to better performance. A total maximum score of 74 is achieved by adding the individual level scores; shoulder maximum 16, middle level maximum score 34 and distal level maximum score 24. In order to provide optimal testing conditions and consistency in endpoint measurements, the functional assessment of PUL was completed at approximately the same time of day.
Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.
Measured: Baseline, Weeks 13, 25, 49 and 73.
Change From Baseline on the PUL Overall Score - Overall Baseline
The PUL scale was used to assess motor performance of the upper limb for individuals with DMD. The PUL scale includes 22 items; an entry item defining the starting functional level, and 21 items subdivided into 3 levels; shoulder (4 items), middle (9 items) and distal (8 items). Scoring options per item may not be uniform and may vary from 0-1 to 0-6, according to the performance, with higher values corresponding to better performance. A total maximum score of 74 is achieved by adding the individual level scores; shoulder maximum 16, middle level maximum score 34 and distal level maximum score 24.
This is the overall change from baseline which included the change since enrolling in parent study B5161002. Overall baseline was defined as the last pre-dose assessment prior to the first day of dosing in study B5161002. Week 1 was counted starting from the study treatment in study B5161002.
Measured: Baseline, Weeks 9,17,25,33,41,49,57,65,73,81,89,97,110,122,146,170.
Change From Baseline on the Six Minute Walk Distance (6MWD) - B5161004 Baseline
The 6MWD evaluated ambulation ability by measuring the distance walked in 6 minutes. In order to provide optimal testing conditions and consistency in endpoint measurements, the functional assessment of 6MWD was completed at approximately the same time of day.
Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.
Measured: Baseline, Weeks 13, 25, 49 and 73.
Change From Baseline on the 6MWD - Overall Baseline
The 6MWD evaluated ambulation ability by measuring the distance walked in 6 minutes. In order to provide optimal testing conditions and consistency in endpoint measurements, the functional assessment of 6MWD was completed at approximately the same time of day. This is the overall change from baseline which included the change since enrolling in the parent study B5161002.
Overall baseline was defined as the last pre-dose assessment prior to the first day of dosing in study B5161002. Week 1 was start of the study treatment in parent study B5161002.
Measured: Baseline,Weeks 9,17,25,33,41,49,57,65,73,81,89,97,110,122,146,170.
Change From Baseline on the Forced Expiratory Volume in One Second (FEV1) - B5161004 Baseline
The FEV1 was recorded as an absolute volume in litres and in terms of predicted values according to age, height, race and gender. The best single FEV1 measurement from a set of 3 was recorded in the database.
Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.
Measured: Baseline, Weeks 13, 25, 49 and 73.
Change From Baseline on the Peak Expiratory Flow Rate (PEFR)- B5161004 Baseline
PEFR was one of the Pulmonary Function Tests (PFTs). Three technically adequate peak expiratory flow rate (PEFR) maneuvers were performed and reported in Litres/Minute (L/min), and the highest single PEFR was reported in the database. In order to provide optimal testing conditions and consistency in endpoint measurements, the functional assessment of PEFR was completed at approximately the same time of day.
Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.
Measured: Baseline, Weeks 13, 25, 49 and 73.
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline
Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, elbow extension, hip abduction and shoulder abduction. 95% Confidence Interval was not calculated when less than or equal to 3 participants' data were available.
Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.
Measured: Baseline, Weeks 13, 25, 49, 73.
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline
Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, elbow extension, hip abduction and shoulder abduction. 95% Confidence Interval was not calculated when less than or equal to 3 participants' data were available.
Overall baseline was defined as the last pre-dose assessment prior to the first day of dosing in study B5161002. Week 1 was start of the study treatment in parent study B5161002.
Measured: Baseline,Weeks 9,17,25,33,41,49,57,65,73,81,89,97,110,122,146,170.
Serum PF-06252616 (Domagrozumab) Concentration Versus Time Summary
Measured: Weeks 1, 25, 49 and 73
Number of Participants With Anti-drug Antibodies (ADA) Development
The criterion for positive result of ADA samples was ADA titer >=1.88. The criterion for negative result of ADA samples was ADA titer <1.88.
Measured: Weeks 1, 25, 49, 73 and Early Termination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2016 (estimated)
- Study start13 Oct 2016
- Primary completion22 Nov 2018
- Study completion22 Nov 2018
Why it stopped: Termination Date: 30Aug2018; Reason for termination: Lack of Efficacy
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Duchenne Muscular DystrophyStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Masking
- None (open label)
- Enrolment
- 59 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02907619
- Sponsor's protocol ID
- B5161004
- Other IDs
- 2016-001615-21, 2016
- Status last verified
- Oct 2020
- First submitted
- 14 Sep 2016
- Last updated
- 23 Nov 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.
Publications
Wagner KR, Abdel-Hamid HZ, Mah JK, Campbell C, Guglieri M, Muntoni F, Takeshima Y, McDonald CM, Kostera-Pruszczyk A, Karachunski P, Butterfield RJ, Mercuri E, Fiorillo C, Bertini ES, Tian C, Statland J, Sadosky AB, Purohit VS, Sherlock SP, Palmer JP, Binks M, Charnas L, Marraffino S, Wong BL. Randomized phase 2 trial and open-label extension of domagrozumab in Duchenne muscular dystrophy. Neuromuscul Disord. 2020 Jun;30(6):492-502. doi: 10.1016/j.nmd.2020.05.002. Epub 2020 May 19.
PubMed 32522498
Study at a glance
From the registry record, last updated by the sponsor on 23 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A MULTICENTER, OPEN-LABEL EXTENSION STUDY TO EVALUATE THE LONG TERM SAFETY OF PF-06252616 IN BOYS WITH DUCHENNE MUSCULAR DYSTROPHY
- ClinicalTrials.gov ID
- NCT02907619
- Acronym / sponsor ID
- B5161004
- Conditions
- Duchenne Muscular Dystrophy
- Keywords
- Duchenne muscular dystrophy, myostatin, open-label
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Termination Date: 30Aug2018; Reason for termination: Lack of Efficacy
- Enrolment
- 59 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- 13 Oct 2016 (actual)
- Primary completion
- 22 Nov 2018 (actual)
- Study completion
- 22 Nov 2018 (actual)
- First posted
- 20 Sep 2016 (estimated)
- Results
- Posted 25 Nov 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is an open-label extension to protocol B5161002 and will provide an assessment of the long term safety, efficacy, pharmacodynamics and pharmacokinetics of intravenous dosing of PF 06252616 in boys with Duchenne muscular dystrophy. Approximately 105 eligible subjects will be assigned to receive a monthly individualized maximum tolerated dose based on their tolerability profile/data from B5161002. This study will not contain a placebo comparator. Subjects will undergo safety evaluations (Laboratory, cardiac monitoring, physical exams, x-ray, MRI), functional capacity evaluations (4 stair climb, range of motion, strength testing, Northstar Ambulatory Assessment, upper limb functional testing, six minute walk test and pulmonary function tests) and pharmacokinetic testing.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PF-06252616 | Experimental | Biological: PF-06252616Either 5mg/kg, 20mg/kg or 40mg/kg will be assigned to a subject based on their maximum tolerated dose from B5161002 |
Who may qualify
- Ages
- 6 to 18 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (7 listed)
- Subjects with Duchenne muscular dystrophy who enrolled and completed study B5161002.
- Signed and dated informed consent document (ICD) indicating that the subject's parent or legal guardian/caregiver has been informed of all pertinent aspects of the study.
- Subjects and their legal guardians/caregivers who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
- Subject have;
Key exclusion criteria (6 listed)
- Unwilling or unable (eg, metal implants) to undergo examination with closed MRI.
- All male subjects who are able to father children and are sexually active and at risk for impregnating a female partner, who are unwilling or unable to use a highly effective method of contraception. In addition, all sexually active male subjects who are unwilling or unable to prevent potential transfer of and exposure to drug through semen to their partners by using a condom consistently and correctly. .
- Subjects who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, or subjects who are related to Pfizer employees directly involved in the conduct of the study.
- Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation.
- Participation in other studies involving investigational drug(s), with the exception of B5161002.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PF-06252616Either 5mg/kg, 20mg/kg or 40mg/kg will be assigned to a subject based on their maximum tolerated dose from B5161002 | Biological | PF-06252616 |
Primary outcome
Number of Participants With Dose Reduced or Temporary Discontinuation Due to AEs
Time frame: 2 Years
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment or usage. Treatment-related AEs were determined by the investigator. The number of participants with dose reduced or temporary discontinuation due to both all-causality and treatment-related AEs are presented below.
Number of Participants With Severe Treatment-Emergent Adverse Events (TEAEs)
Time frame: 2 Years
An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment or usage. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment. Severe TEAEs were TEAEs that interfered significantly with participants' usual function. Treatment-related TEAEs were determined by the investigator. The number of participants with severe all-causality and treatment-related TEAEs are presented below.
Number of Participants Who Discontinued From the Study Due to TEAEs
Time frame: 2 Years
An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment or usage. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment. Treatment-related TEAEs were determined by the investigator. The number of participants who discontinued from the study due to both all-causality and treatment-related TEAEs are presented below.
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hematology
Time frame: 2 Years
Hematology evaluation included: hemoglobin, hematocrit, red blood cell (RBC) count, platelets, RBC morphology, white blood cell (WBC) count, absolute lymphocytes, absolute atypical lymphocytes, absolute total neutrophils, absolute total neutrophils count, absolute band cells, absolute basophils, absolute eosinophils and absolute monocytes. Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. (ULN=Upper Limit of Normal; LLN=Lower Limit of Normal).
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Coagulation
Time frame: 2 Years
Coagulation evaluation included activated partial thromboplastin time (aPTT) and prothrombin time (PT). (ULN=Upper Limit of Normal). Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004.
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Liver Function
Time frame: 2 Years
Liver function evaluation included: total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), alkaline phosphatase, total protein, albumin and glutamate dehydrogenase. Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. (LLN=Lower Limit of Normal; ULN=Upper Limit of Normal).
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Renal Function
Time frame: 2 Years
Renal function evaluation included: blood urea nitrogen (BUN), creatinine and uric acid. Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. (ULN=Upper Limit of Normal).
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Electrolytes
Time frame: 2 Years
Electrolytes evaluation included: sodium, potassium, chloride, calcium, phosphate and bicarbonate. Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. (LLN=Lower Limit of Normal, ULN=Upper Limit of Normal).
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hormones
Time frame: 2 Years
Hormone evaluations included free thyroxine (T4), thyroid stimulating hormone (TSH), lutenizing hormone (LH), follicle stimulating hormone (FSH), and androstenedione. Numbers of participants with abnormalities of LH, FSH and androstenedione were reported in different age groups. Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. (LLN=Lower Limit of Normal, ULN=Upper Limit of Normal).
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Clinical Chemistry
Time frame: 2 Years
Clinical chemistry evaluation included glucose, creatine kinase (CK), troponin I, amylase, iron binding capacity, unsaturated iron binding capacity, transferrin saturation, iron and ferritin. Number of participants with iron abnormalities was reported in different age groups. Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. (LLN=Lower Limit of Normal, ULN=Upper Limit of Normal).
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Urinalysis
Time frame: 2 Years
Urinalysis Microscopy included: urine red blood cell (RBC), urine white blood cell (WBC), urine uric acid crystals, urine calcium oxalate crystals, urine amorphous crystals, urine bacteria, urine microscopic exam. Urinalysis Dipstick included: urine pH, urine glucose, urine ketones, urine protein, urine blood/hemoglobin, urine nitrite, urine leukocyte esterase. Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004.
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Fecal Blood
Time frame: 2 Years
Number of participants with blood detected in fecal samples is presented. Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. (ULN=Upper Limit of Normal).
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline
Time frame: Baseline, Weeks 13, 25, 37, 49, 61, 73 and 85.
Participants were asked to fast for at least 8 hours prior to collection of blood to evaluate serum iron, serum ferritin and % transferrin saturation. The unit of iron was mcg/dL; the unit of ferritin was ng/mL; the unit of %transferrin saturation was %. Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.
Number of Participants With Significant Results of Physical Examinations Including Nose and Throat Mucosal Examinations
Time frame: 2 Years
Physical examinations were conducted by a physician, trained physician's assistant, or nurse practitioner as acceptable according to local regulation. A targeted nose and throat mucosal exam was performed to monitor for any signs of mucosal telangiectasias. The clinically significant physical examination results were determined by the investigator.
Summary of Pubertal Development by Tanner Stage
Time frame: Screening, Baseline, Week 49.
Tanner staging was performed before the first dose of this study to monitor for signs of accelerated sexual development. The physical changes in pubertal development (pubic hair, penis and testes) were assessed using the system described by Marshall and Tanner. Stage 1 is preadolescent, Stages 2, 3, and 4 are initiation of puberty and Stage 5 is mature adult. Details about the system can be referred to Tanner JM. Growth at Adolescence. Blackwell Scientific Publications 1962; 2nd edition. Participant's Week 97 visit within study B5161002 (parent study) was collected as screening data. Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.
Summary of Testicular Volume
Time frame: Screening, Baseline, Week 49.
Testicular volume was used to monitor pubertal development. Participant's Week 97 visit within Study B5161002 (parent study) was collected as screening data in current study. Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.
Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria - B5161004 Baseline
Time frame: 2 Years
The number of participants pre-dose supine blood pressure and pulse rate meeting categorical summarization criteria are recorded in this table. Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. (DBP=diastolic blood pressure, SBP=systolic blood pressure; The unit for blood pressure is: mmHg, the unit for pulse rate is: beats per minute [BPM])
Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria - Overall Baseline
Time frame: 2 Years
The number of participants with data of pre-dose supine blood pressure meeting categorical summarization were recorded in this table. Overall Baseline was defined as the last pre-dose assessment prior to the first day of dosing in study B5161002. (DBP=diastolic blood pressure, SBP=systolic blood pressure; The unit for blood pressure is: mmHg).
Number of Participants With Post-Baseline ECG Data Meeting Categorical Summarization Criteria - B5161004 Baseline
Time frame: 2 Years
QTcF=QT/(60/Hour)**(1/3). Means of replicates were used in the calculations. QT=time between the start of the Q wave and the end of the T wave in the heart's electrical cycle; QTcF=corrected QT (Fridericia correction). All scheduled ECGs were performed after the participant had rested quietly for at least 10 minutes in a supine position. Baseline was defined as the average of the last triplicate pre-dose measurements prior to Day 1 in B5161004.
Number of Participants With Post-Baseline ECG Data Meeting Categorical Summarization Criteria - Overall Baseline
Time frame: 2 Years
QT=time between the start of the Q wave and the end of the T wave in the heart's electrical cycle; QTcF=corrected QT (Fridericia correction). All scheduled ECGs were performed after the participant had rested quietly for at least 10 minutes in a supine position. Overall baseline was defined as the average of the last triplicate pre-dose measurements prior to the first day of dosing in study B5161002.
Number of Participants With Iron Accumulation Data Meeting Categorical Summarization Criteria
Time frame: Screening and Week 49.
Liver Magnetic Resonance Imaging (MRIs) were sent to an independent central radiology imaging facility for calculation of the average R2* value which was used to monitor for iron accumulation in the liver. Mean R2* values had been used in the calculations. Normal: R2* <= 75 Hz at 1.5 T or <=139 Hz at 3.0 T; Above Normal: R2* > 75 Hz and <= 190 Hz at 1.5 T or R2* > 139 Hz and <= 369 Hz at 3.0 T Mild overload: R2* > 190 Hz at 1.5 T or R2* > 369 Hz at 3.0 T Data from participant's Week 93 visit in Study B5161002 (parent study) were used for screening in the current study.
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) by Cardiac MRI - B5161004 Baseline
Time frame: Baseline and Week 49.
The LVEF was the ratio of blood ejected during systole to blood in the ventricle at the end of diastole. LVEF was measured by cardiac magnetic resonance imaging (MRI) or echocardiography. The same method of cardiac imaging was used consistently for each participant. Cardiac MRIs were read by a central imaging vendor, while echocardiograms were read locally (at each site). The table presents the results from cardiac MRIs. Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) by Cardiac MRI - Overall Baseline
Time frame: Baseline, Weeks 49, 97, 146.
The LVEF was the ratio of blood ejected during systole to blood in the ventricle at the end of diastole. LVEF was measured by cardiac magnetic resonance imaging (MRI) or echocardiography. The same method of cardiac imaging was used consistently for each participant. Cardiac MRIs were read by a central imaging vendor, while echocardiograms were read locally (at each site). The table presents the results from cardiac MRIs. Overall baseline was defined as the last pre-dose assessment prior to the first day of dosing in study B5161002. Week 1 was counted starting from the study treatment in study B5161002.
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) by Echocardiogram - B5161004 Baseline
Time frame: Baseline, Week 49.
The LVEF was the ratio of blood ejected during systole to blood in the ventricle at the end of diastole. LVEF was measured by cardiac magnetic resonance imaging (MRI) or echocardiography. The same method of cardiac imaging was used consistently for each participant. Cardiac MRIs were read by a central imaging vendor, while echocardiograms were read locally (at each site). The table presents the results from echocardiograms. Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) by Echocardiogram - Overall Baseline
Time frame: Baseline, Weeks 49, 97, 146.
The LVEF was the ratio of blood ejected during systole to blood in the ventricle at the end of diastole. LVEF was measured by cardiac magnetic resonance imaging (MRI) or echocardiography. The same method of cardiac imaging was used consistently for each participant. Cardiac MRIs were read by a central imaging vendor, while echocardiograms were read locally (at each site). The table presents the results from echocardiograms. Overall baseline was defined as the last pre-dose assessment prior to the first day of dosing in study B5161002. Week 1 was counted starting from the study treatment in study B5161002.
Bone Age to Chronological Age Ratio
Time frame: Baseline and Week 49.
Bone age assessment was evaluated by the ratio of the bone age to the chronological age using the X rays of the hand and wrist. Ratio of bone age to chronological age was calculated by bone age/chronological age at scan date. Chronological age at scan date was calculated by (scan date - date of birth + 1)/365.25. Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.
Whole Body and Spine DXA: Bone Mineral Density Z-Score, Height Adjusted Over Time
Time frame: Screening (Week 97 visit within parent study B5161002) and Week 49
Bone mineral density (BMD) was monitored by dual energy x-ray absorptiometry (DXA). DXA scans were obtained to evaluate bone mineral density of the spine and whole body without head. The height adjusted Z-score presented below is the number of standard deviations which compares the BMD of the participant to the average BMD matched for their age, sex and ethnicity. If the Z-score was -2 standard deviations or lower, the result was "below the expected range for age". If the Z-score was above -2 standard deviations, the result was "within the expected range for age".
Number of Participants With Suicidal Ideation or Suicidal Behavior
Time frame: 2 Years
The Columbia Suicide Severity Rating Scale (C-SSRS) was performed to identify the risk of suicide ideation or behavior. C-SSRS was conducted with the participant's caregiver/legal guardian on the participant's behalf throughout the study, rather than administering this evaluation directly with the study participants. If at any visit the participant endorsed a 4 or 5 on the C-SSRS ideation section or reported any suicidality behavior, then an evaluation of suicide risk (risk assessment) had to be completed and the participant must have been discontinued. The significant result of C-SSRS was determined by the investigator.
22 secondary outcomes
Change From Baseline on the 4 Stair Climb (4SC) - B5161004 Baseline
Time frame: Baseline, Weeks 13, 25, 49, 73.
Change From Baseline on the 4SC - Overall Baseline
Time frame: Baseline, Weeks 9,17,25,33,41,49,57,65,73,81,89,97,110,122,146,170.
Change From Baseline on the Forced Vital Capacity (FVC) - B5161004 Baseline
Time frame: Baseline, Weeks 13, 25, 49 and 73.
Change From Baseline on the FVC - Overall Baseline
Time frame: Baseline, Weeks 9,17,25,33,41,49,57,65,73,81,89,97,110,122,146,170.
Change From Baseline on the Northstar Ambulatory Assessment (NSAA) Score - B5161004 Baseline
Time frame: Baseline, Weeks 13, 25, 49, 73.
Change From Baseline on the NSAA Score - Overall Baseline
Time frame: Baseline, Weeks 9,17,25,33,41,49,57,65,73,81,89,97,110,122,146,170.
Change From Baseline on the NSAA - Time to Stand From Supine - B5161004 Baseline
Time frame: Baseline, Weeks 13, 25, 49, 73.
Change From Baseline on the NSAA - Time to Stand From Supine - Overall Baseline
Time frame: Baseline, Weeks 9,17,25,33,41,49,57,65,73,81,89,97,110,122,146,170.
Change From Baseline on the NSAA - Time to Complete 10 m Run/Walk - B5161004 Baseline
Time frame: Baseline, Weeks 13, 25, 49, 73.
Change From Baseline on the NSAA - Time to Complete 10 m Run/Walk - Overall Baseline
Time frame: Baseline, Weeks 9,17,25,33,41,49,57,65,73,81,89,97,110,122,146,170.
Change From Baseline on the Ankle Range of Motion (ROM) - B5161004 Baseline
Time frame: Baseline, Weeks 13, 25, 49 and 73.
Change From Baseline on the Ankle ROM - Overall Baseline
Time frame: Baseline, Weeks 9,17,25,33,41,49,57,65,73,81,89,97,110,122,146,170.
Change From Baseline on the Performance of Upper Limb (PUL) Overall Score - B5161004 Baseline
Time frame: Baseline, Weeks 13, 25, 49 and 73.
Change From Baseline on the PUL Overall Score - Overall Baseline
Time frame: Baseline, Weeks 9,17,25,33,41,49,57,65,73,81,89,97,110,122,146,170.
Change From Baseline on the Six Minute Walk Distance (6MWD) - B5161004 Baseline
Time frame: Baseline, Weeks 13, 25, 49 and 73.
Change From Baseline on the 6MWD - Overall Baseline
Time frame: Baseline,Weeks 9,17,25,33,41,49,57,65,73,81,89,97,110,122,146,170.
Change From Baseline on the Forced Expiratory Volume in One Second (FEV1) - B5161004 Baseline
Time frame: Baseline, Weeks 13, 25, 49 and 73.
Change From Baseline on the Peak Expiratory Flow Rate (PEFR)- B5161004 Baseline
Time frame: Baseline, Weeks 13, 25, 49 and 73.
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline
Time frame: Baseline, Weeks 13, 25, 49, 73.
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline
Time frame: Baseline,Weeks 9,17,25,33,41,49,57,65,73,81,89,97,110,122,146,170.
Serum PF-06252616 (Domagrozumab) Concentration Versus Time Summary
Time frame: Weeks 1, 25, 49 and 73
Number of Participants With Anti-drug Antibodies (ADA) Development
Time frame: Weeks 1, 25, 49, 73 and Early Termination
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Nov 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32522498Wagner KR, Abdel-Hamid HZ, Mah JK, Campbell C, Guglieri M, Muntoni F, Takeshima Y, McDonald CM, Kostera-Pruszczyk A, Karachunski P, Butterfield RJ, Mercuri E, Fiorillo C, Bertini ES, Tian C, Statland J, Sadosky AB, Purohit VS, Sherlock SP, Palmer JP, Binks M, Charnas L, Marraffino S, Wong BL. Randomized phase 2 trial and open-label extension of domagrozumab in Duchenne muscular dystrophy. Neuromuscul Disord. 2020 Jun;30(6):492-502. doi: 10.1016/j.nmd.2020.05.002. Epub 2020 May 19.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
47 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PF-06252616 in people with Duchenne Muscular Dystrophy, run by Pfizer at 47 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 23 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 47 sites in United States, Italy, Canada, United Kingdom, Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Nov 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Dose Reduced or Temporary Discontinuation Due to AEs (time frame: 2 Years). The study lists 28 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02907619, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Nov 2020.