AchondroplasiaPhase 2NCT04638153
A Study Of Safety, Tolerability And Effectiveness Of Recifercept In Children With Achondroplasia
A Phase 2 study testing Recifercept in people with Achondroplasia, run by Pfizer at 16 sites in 8 countries.
Trial summary
Approximately 63 participants will be randomized to one of three doses to receive Recifercept either Low Dose Medium Dose High Dose Participants will will attend the clinic at baseline and at Day 1, 4, 8, 15, 29 \& then Month 2, 3 6, 9 \& 12. Read more about this study
- Who is it for?
- Ages 3 months to 10 years
- Conditions the study is for
- Achondroplasia
- What is being tested?
- Recifercept
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 16 sitesin 8 countries
- Study dates
- 2 Dec 2020to 27 Mar 2023
- 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 3 months to 10 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Main cohort: Aged ≥2 years to <11 years (up to the day before 11th birthday inclusive) at time of enrollment; or exploratory cohort: aged ≥3 months to <2 years (up to the day before 2nd birthday inclusive) at time of enrollment
- Documented, confirmed genetic diagnosis of achondroplasia from historical medical records prior to entry into this trial (test must have been performed at a laboratory fully accredited for genetic testing under local regulations).
- Completed the C4181001 natural history study with at least 2 valid height/length measurements (at least 3 months apart) prior to enrollment in this study. One of these measurement timepoints must be within the 3 months prior to enrollment in C4181005.
- Tanner stage 1 based on investigator assessment during physical examination (must include assessment of breast development for females, testicular stage for males).
- Able to stand independently for height measurements (if ≥2 years of age at enrollment).
- If aged <2 years at enrollment, has a documented historical MRI brain/cervical spine performed in the previous 12 months.
Who cannot join
- Presence of co-morbid conditions or circumstances that, in the opinion of the investigator, would affect interpretation of growth data or ability to complete the trial procedures.
- Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
- Presence of severe obesity (BMI >95th percentile on Hoover-Fong BMI charts) [Hoover-Fong et al, 2008].14
- Known closure of long bone growth plates (cessation of height growth).
- Body weight <7 kg or >30 kg.
- Moderate or severe renal impairment CrCL GFR <60 mL/min/1.73m2 (Calculated GFR based on updated "bedside" Schwartz formula for pediatric patients (CrCL (mL/min/1.73 m2) = 0.413 * Height (cms)/ Serum cr (mg/dL) or hepatic impairment (AST/ALT >1.5 ULN).
Show all 16Show fewer
- History of hypersensitivity to study intervention or any excipients.
- History of any prior treatment with human growth hormone or related products (including insulin-like growth factor 1 [IGF-1]).
- History of receipt of any treatment that are known to potentially affect growth (including oral steroids >5 days in the last 6 months, high dose inhaled corticosteroids (>800 mcg/day beclametasone equivalent) and medication for attention deficit hyperactivity disorder).
- History of limb lengthening surgery (defined as distraction osteogenesis/Ilizarov/callostasis technique following submetaphyseal osteotomy to extend bone length).
- Any limb lengthening/corrective orthopaedic surgery planned at any point during the trial period.
- Less than 6 months since fracture or surgical procedure of any bone determined from the screening visit date.
- Presence of any internal guided growth plates/devices.
- History of removal of internal guided growth plates/devices within less than 6 months.
- History of receipt of any investigational product for achondroplasia or that may affect growth/interpretation of growth parameters.
- History of receipt of an investigational product (not for achondroplasia/growth affecting) within the last 30 days or 5 half-lives (whichever is longer).
Trial locations and contacts
16 sites in 8 countries.
16 sites in 8 countries
United States6 sites
Ocean Sleep Medicine
Aliso Viejo, California, 92656
Texas Children's Hospital
Houston, Texas, 77030
Ocean Sleep Medicine
Irvine, California, 92604
MemorialCare Sleep Disorders Center at Long Beach Memorial Medical Center
Long Beach, California, 90806
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Torrance, California, 90502
Nemours Alfred I duPont Hospital for Children
Wilmington, Delaware, 19803
Australia2 sites
Murdoch Children's Research Institute
Melbourne, Victoria, 3052
Murdoch Children's Research Institute
Parkville, Victoria, 3052
Belgium2 sites
Universitair Ziekenhuis Antwerpen
Edegem, 2650
Universitaire Ziekenhuizen Leuven (UZ Leuven)
Leuven, 3000
Japan2 sites
Okayama University Hospital
Okayama, 700-8558
Osaka University Hospital
Suita, Osaka, 565-0871
Italy1 site
Fondazione Policlinico Universitario Agostino - Gemelli IRCCS
Roma, 00168
Portugal1 site
Centro Hospitalar e Universitário de Coimbra - Hospital Pediátrico
Coimbra, 3000-602
About this study
Official title: A PHASE 2 MULTIPLE DOSE, RANDOMIZED STUDY TO ASSESS THE SAFETY, TOLERABILITY, PHARMACOKINETICS AND EFFICACY OF RECIFERCEPT IN CHILDREN WITH ACHONDROPLASIA
Approximately 63 participants will be randomized to one of three doses to receive Recifercept either
- Low Dose
- Medium Dose
- High Dose
Read more
Participants will will attend the clinic at baseline and at Day 1, 4, 8, 15, 29 \& then Month 2, 3 6, 9 \& 12. Assessments include safety, blood sampling, physical examination, vital signs, anthropometric body measurements \& patient/caregiver quality of life questionnaires
Participants will received treatment with Recifercept for 12 months. All participants who complete the study and in the opinion of the investigator, continue to have a positive risk:benefit profile, will be offered to enroll into an open-label extension (OLE) study.
A PK cohort will include 12 participants who will randomly receive a single dose of 3 mg/kg of Phase 2 study (process 1c) formulation and a single dose of 3 mg/kg of the proposed Phase 3 (process 2) study formulation in a cross over study. Dose of the cohort could be changed due to emerging safety and efficacy data in the study.
Read the detailed description
This is a phase 2 randomized, 3 arm (3 active doses of Recifercept), parallel group dose finding study of safety, tolerability, PK and efficacy
The total number of participants is 63 in 2 age straified cohorts of 0-2 years and 6-10 years old.
The study will enroll approximately 54 children with achondroplasia aged 2-10 years (inclusive) who will be enrolled and randomized to receive one of three doses of recifercept
- Low Dose
- Medium Dose
- High Dose
A total of 18 participants will be enrolled per dose 18 per dosesuch that at least 15 participants per dose are evaluable. An interim analysis is planned when at least 15 participants per dose aged ≥2 to <11 years have received 6 months of treatment with recifercept. eDMC will review safety, PK and efficacy data to confirm ongoing positive benefit:risk in participants.
Additionally, an exploratory cohort of approximately 9 children with achondroplasia, ages 0-2 years, will be enrolled later in the study (n=3 per dose).
Enrollment will follow an age and dose-staggered approach (descending age and ascending dose) with review of safety and PK data by the study team before progression to the next enrollment block If certain pre-defined safety signals occur then a meeting of the eDMC will be convened to make a decision on progression of enrollment. The PK data collected in block A will be used in the PopPK model (developed using healthy adult data) to confirm the dosing for younger children (ie, ≥2 to <6 years and 0-<2 years).
Participants will will attend the clinic at baseline and at Day 1, 4, 8, 15, 29 \& then Month 2, 3 6, 9 \& 12. Assessments include safety, blood sampling, physical examination, vital signs, anthropometric body measurements \& patient/caregiver quality of life questionnaires
All participants will receive recifercept for 12 months. All participants who complete the study and in the opinion of the investigator, continue to have a positive risk:benefit profile, will be offered to enroll into an open-label extension (OLE) study.
PK Cohort:
Multiple changes have been made in the manufacturing process of the drug product (process 2) which will be used in Phase 3. Therefore, an additional PK cohort (at selected sites only) has been added, to evaluate the PK of Phase 2 formulation (process 1c) and Phase 3 formulation (process 2).
PK Cohort:
At selected sites only, an additional PK cohort has been added to evaluate the PK of two recifercept formulations. A total of 12 children with achondroplasia aged 2- <11 years will be enrolled in the PK cohort (6 in each treatment sequence). Each participant will receive 2 treatments (3 mg/kg Phase 2 formulation [process 1c] and 3 mg/kg Phase 3 formulation [process 2]) in a randomized manner. Dose of the cohort could be changed due to emerging safety and efficacy data in the study.
PK samples collected following each dose will be analyzed to evaluate the exposures of two formulations.
- Conditions
- Achondroplasia
- Being tested
- Recifercept
- Keywords
- Skeletal Dysplasia
- Medical subject headings
- Achondroplasia, Mucopolysaccharidosis IV
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ReciferceptBiological
Recifercept
| Study group | Role | What they receive |
|---|---|---|
| Low Dose | Experimental | Low Dose Receives: Biological: Recifercept |
| Medium Dose | Experimental | Medium Dose Receives: Biological: Recifercept |
| High Dose | Experimental | High Dose Receives: Biological: Recifercept |
| PK Phase 2 Formulation | Experimental | Phase 2 formulation [process 1c] 3mg/kg Receives: Biological: Recifercept |
| PK Phase 3 Formulation | Experimental | Phase 3 formulation [process 2] 3mg/kg Receives: Biological: Recifercept |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs)
Treatment-related AE was any untoward medical occurrence attributed to study intervention in a participant who received study intervention. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AE is defined as an AE with onset date occurring during the on-treatment period. Relatedness to recifercept was assessed by the investigator (Yes/No).
Measured: The first dose up to 28 to 35 days after the last dose of study intervention (13 months)
Least Square Mean of Change From Baseline Height Growth at Month 3, Month 6, Month 9, and Month 12
Height growth was defined as the ratio of observed change from baseline in standing height to the expected change from baseline in the reference population.
Measured: Baseline, Month 3, Month 6, Month 9, and Month 12
Secondary outcomes (21)
Change From Baseline in Pulse Rate at Month 3, Month 6, Month 9, and Month 12
Pulse rate measurements were preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (eg, television, cell phones) where possible (with consideration of the age of the child). Pulse rate was summarized by treatment in accordance with the sponsor reporting standards.
Measured: Baseline, Month 3, Month 6, Month 9, and Month 12
Change From Baseline in Respiratory Rate at Month 3, Month 6, Month 9, and Month 12
Respiratory rate was obtained with participant in the seated position, after having sat calmly for at least 5 minutes. Respiratory rate was summarized by treatment in accordance with the sponsor reporting standards.
Measured: Baseline, Month 3, Month 6, Month 9, and Month 12
Change From Baseline in Blood Pressure at Month 3, Month 6, Month 9, and Month 12
Blood pressure measurements were preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions (eg, television, cell phones) where possible (with consideration of the age of the child). Supine systolic blood pressure (SBP) and diastolic blood pressure (DBP) were summarized by treatment in accordance with the sponsor reporting standards.
Measured: Baseline, Month 3, Month 6, Month 9, and Month 12
Change From Baseline in Temperature at Month 3, Month 6, Month 9, and Month 12
Temperature was obtained with participant in the seated position, after having sat calmly for at least 5 minutes. Temperature measurements were summarized by treatment in accordance with the sponsor reporting standards.
Measured: Baseline, Month 3, Month 6, Month 9, and Month 12
Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12
A physical examination included, at a minimum, assessments of the cardiovascular, respiratory, gastrointestinal systems and skin. Physical examination assessments were summarized by treatment in accordance with the sponsor reporting standards.
Measured: Month 3, Month 6, Month 9, and Month 12
Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)
Participants with laboratory abnormalities that met pre-specified criteria included following parameters: hematology (corpuscular volume, corpuscular hemoglobin, corpuscular hemoglobin concentration, platelet, leukocytes, lymphocytes, neutrophils, eosinophils, and monocytes), and chemistry (bilirubin, alkaline phosphatase, albumin, urea nitrogen, urate, potassium, phosphate, bicarbonate).
Measured: Baseline to Month 12
Pre-Dose Serum Concentration (Ctrough) of Recifercept
Ctrough was defined as pre-dose serum concentration during dosing and observed directly from data.
Measured: Pre-dose on Day(s) 4, 8, 15, 29, 61, 91, 183, 273, 365
Number of Participants With Positive Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) of Recifercept
The immunogenicity was measured by presence of ADA and NAb in participants treated with recifercept and summarized by dose regimen.
Measured: The first dose up to 28 to 35 days after the last dose of study intervention (13 months)
Change From Baseline in Sitting/Standing Height Ratio at Month 3, Month 6, Month 9, and Month 12
Sitting/standing height ratio was the ratio of sitting height to standing height.
Measured: Baseline, Month 3, Month 6, Month 9, and Month 12
Least Square Mean of Change From Baseline Arm Span to Standing Height/Length Difference at Month 3, Month 6, Month 9, and Month 12
Arm span to standing height/length difference was the difference between arm span and standing height.
Measured: Baseline, Month 3, Month 6, Month 9, and Month 12
Change From Baseline in Knee Height : Lower Segment Ratio at Month 3, Month 6, Month 9, and Month 12
Knee height : lower segment ratio was the ratio of knee to heel length to the difference between standing height and sitting height.
Measured: Baseline, Month 3, Month 6, Month 9, and Month 12
Change From Baseline in Occipito-Frontal Circumference at Month 3, Month 6, Month 9, and Month 12
Head circumference or the occipito-frontal circumference is the greatest of the cranial dimensions which passes around the forehead anteriorly and the external occipital protruberance posteriorly. It is a routine part of the physical examination of a child and is of great importance in detecting abnormal patterns of cranial growth. Occipito-frontal circumference data were summarized for each treatment arm.
Measured: Baseline, Month 3, Month 6, Month 9, and Month 12
Change From Baseline in Occipito-Frontal to Occipito-Mid-Face Ratio at Month 3, Month 6, Month 9, and Month 12
Ratio of occipito-frontal distance to occipito-mid-face measurements was summarized for each treatment arm.
Measured: Baseline, Month 3, Month 6, Month 9, and Month 12
Change From Baseline in Height Standard Deviation Score (Z-Score) at Month 3, Month 6, Month 9, and Month 12
Height Standard Deviation Score (SDS) (z-score) was calculated as the difference between mean observed standing height at each visit and mean value of reference population divided by standard deviation of reference population. SDS indicates how similar the participant was to the reference population.
Measured: Baseline, Month 3, Month 6, Month 9, and Month 12
Change From Baseline in Fixed Flexion Angles at Elbow at Month 3, Month 6, Month 9, and Month 12
Fixed flexion angles at elbow data were presented for each treatment arm. An average of a participant's elbow extension measurements over a visit was computed.
Measured: Baseline, Month 3, Month 6, Month 9, and Month 12
Change From Baseline in Body Mass Index (BMI) at Month 3, Month 6, Month 9, and Month 12
Body Mass Index (BMI) = Weight (kg)/[(Standing Height (m))^2]. Standing height and weight were averaged over a visit before BMI was computed.
Measured: Baseline, Month 3, Month 6, Month 9, and Month 12
Change From Baseline in Waist : Chest Circumference Ratio at Month 9 and Month 12
Waist : Chest Ratio = Waist Circumference / Chest Circumference. Waist and chest circumference were averaged over a visit before waist : chest circumference ratio was computed.
Measured: Baseline, Month 9, and Month 12
Change From Baseline in Apnea-Hypopnea Index (AHI) at Month 12
The apnea-hypopnea index (AHI) is the average of the apneic and hypopneic episodes per hour of sleep, which is measured to assess obstructive sleep apnea (OSA). An AHI score of 1 to 4.9 events/hour is mild OSA, 5 to 9.9 events/hour is moderate, and more than 9 events/hour is severe in pediatric population.
Measured: Baseline and Month 12
Change From Baseline in Desaturation Index at Month 12
Desaturation index is one of the polysomnography parameters to assess obstructive sleep apnea. It refers to the average number of desaturation episodes occurring per hour, where desaturation episodes are defined as a decrease in the mean oxygen saturation of ≥3% (over the last 120 seconds) that lasts for at least 10 seconds.
Measured: Baseline and Month 12
Change From Baseline in Polysomnography Other Parameters at Month 12
Polysomnography refers to a systematic process used to collect physiologic parameters during sleep. Polysomnography other parameters included total sleep time spent with oxygen saturation (SaO2) < 90% (T90), total sleep time spent with end-tidal carbon dioxide (EtCO2) >50 mm Hg.
Measured: Baseline and Month 12
Change From Baseline in SaO2 Nadir at Month 12
SaO2 measures the percentage of oxyhemoglobin (oxygen-bound hemoglobin) in the blood. SaO2 nadir refers to lowest SaO2.
Measured: Baseline and Month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2020
- Study start2 Dec 2020
- Primary completion16 Jan 2023
- Study completion27 Mar 2023
Why it stopped: The study was terminated due to lack of efficacy at any of the tested doses on 18th November 2022. The decision to terminate the study is not related to a safety concern.
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 AchondroplasiaStudies 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 60 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
- NCT04638153
- Sponsor's protocol ID
- C4181005
- Other IDs
- 2020-001189-13
- Status last verified
- Jan 2024
- First submitted
- 15 Sep 2020
- Last updated
- 15 Feb 2024
- 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
Qiao W, Boucher M, Slade A, Dawra VK. Natural disease course modeling of achondroplasia to evaluate the efficacy of recifercept in the absence of a placebo control arm in phase II study. CPT Pharmacometrics Syst Pharmacol. 2024 Jul;13(7):1103-1116. doi: 10.1002/psp4.13143. Epub 2024 Apr 29.
PubMed 38685585
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A PHASE 2 MULTIPLE DOSE, RANDOMIZED STUDY TO ASSESS THE SAFETY, TOLERABILITY, PHARMACOKINETICS AND EFFICACY OF RECIFERCEPT IN CHILDREN WITH ACHONDROPLASIA
- ClinicalTrials.gov ID
- NCT04638153
- Acronym / sponsor ID
- C4181005
- Conditions
- Achondroplasia
- Keywords
- Skeletal Dysplasia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated due to lack of efficacy at any of the tested doses on 18th November 2022. The decision to terminate the study is not related to a safety concern.
- Enrolment
- 60 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- 2 Dec 2020 (actual)
- Primary completion
- 16 Jan 2023 (actual)
- Study completion
- 27 Mar 2023 (actual)
- First posted
- 20 Nov 2020 (actual)
- Results
- Posted 15 Feb 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Approximately 63 participants will be randomized to one of three doses to receive Recifercept either
- Low Dose
- Medium Dose
- High Dose
Participants will will attend the clinic at baseline and at Day 1, 4, 8, 15, 29 \& then Month 2, 3 6, 9 \& 12. Assessments include safety, blood sampling, physical examination, vital signs, anthropometric body measurements \& patient/caregiver quality of life questionnaires
Participants will received treatment with Recifercept for 12 months. All participants who complete the study and in the opinion of the investigator, continue to have a positive risk:benefit profile, will be offered to enroll into an open-label extension (OLE) study.
A PK cohort will include 12 participants who will randomly receive a single dose of 3 mg/kg of Phase 2 study (process 1c) formulation and a single dose of 3 mg/kg of the proposed Phase 3 (process 2) study formulation in a cross over study. Dose of the cohort could be changed due to emerging safety and efficacy data in the study.
Detailed description
This is a phase 2 randomized, 3 arm (3 active doses of Recifercept), parallel group dose finding study of safety, tolerability, PK and efficacy
The total number of participants is 63 in 2 age straified cohorts of 0-2 years and 6-10 years old.
The study will enroll approximately 54 children with achondroplasia aged 2-10 years (inclusive) who will be enrolled and randomized to receive one of three doses of recifercept
- Low Dose
- Medium Dose
- High Dose
A total of 18 participants will be enrolled per dose 18 per dosesuch that at least 15 participants per dose are evaluable. An interim analysis is planned when at least 15 participants per dose aged ≥2 to <11 years have received 6 months of treatment with recifercept. eDMC will review safety, PK and efficacy data to confirm ongoing positive benefit:risk in participants.
Additionally, an exploratory cohort of approximately 9 children with achondroplasia, ages 0-2 years, will be enrolled later in the study (n=3 per dose).
Enrollment will follow an age and dose-staggered approach (descending age and ascending dose) with review of safety and PK data by the study team before progression to the next enrollment block If certain pre-defined safety signals occur then a meeting of the eDMC will be convened to make a decision on progression of enrollment. The PK data collected in block A will be used in the PopPK model (developed using healthy adult data) to confirm the dosing for younger children (ie, ≥2 to <6 years and 0-<2 years).
Participants will will attend the clinic at baseline and at Day 1, 4, 8, 15, 29 \& then Month 2, 3 6, 9 \& 12. Assessments include safety, blood sampling, physical examination, vital signs, anthropometric body measurements \& patient/caregiver quality of life questionnaires
All participants will receive recifercept for 12 months. All participants who complete the study and in the opinion of the investigator, continue to have a positive risk:benefit profile, will be offered to enroll into an open-label extension (OLE) study.
PK Cohort:
Multiple changes have been made in the manufacturing process of the drug product (process 2) which will be used in Phase 3. Therefore, an additional PK cohort (at selected sites only) has been added, to evaluate the PK of Phase 2 formulation (process 1c) and Phase 3 formulation (process 2).
PK Cohort:
At selected sites only, an additional PK cohort has been added to evaluate the PK of two recifercept formulations. A total of 12 children with achondroplasia aged 2- <11 years will be enrolled in the PK cohort (6 in each treatment sequence). Each participant will receive 2 treatments (3 mg/kg Phase 2 formulation [process 1c] and 3 mg/kg Phase 3 formulation [process 2]) in a randomized manner. Dose of the cohort could be changed due to emerging safety and efficacy data in the study.
PK samples collected following each dose will be analyzed to evaluate the exposures of two formulations.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Low Dose | Experimental | Biological: ReciferceptLow Dose |
| Medium Dose | Experimental | Biological: ReciferceptMedium Dose |
| High Dose | Experimental | Biological: ReciferceptHigh Dose |
| PK Phase 2 Formulation | Experimental | Biological: ReciferceptPhase 2 formulation [process 1c] 3mg/kg |
| PK Phase 3 Formulation | Experimental | Biological: ReciferceptPhase 3 formulation [process 2] 3mg/kg |
Who may qualify
- Ages
- 3 months to 10 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Main cohort: Aged ≥2 years to <11 years (up to the day before 11th birthday inclusive) at time of enrollment; or exploratory cohort: aged ≥3 months to <2 years (up to the day before 2nd birthday inclusive) at time of enrollment
- Documented, confirmed genetic diagnosis of achondroplasia from historical medical records prior to entry into this trial (test must have been performed at a laboratory fully accredited for genetic testing under local regulations).
- Completed the C4181001 natural history study with at least 2 valid height/length measurements (at least 3 months apart) prior to enrollment in this study. One of these measurement timepoints must be within the 3 months prior to enrollment in C4181005.
- Tanner stage 1 based on investigator assessment during physical examination (must include assessment of breast development for females, testicular stage for males).
- Able to stand independently for height measurements (if ≥2 years of age at enrollment).
Key exclusion criteria (16 listed)
- Presence of co-morbid conditions or circumstances that, in the opinion of the investigator, would affect interpretation of growth data or ability to complete the trial procedures.
- Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
- Presence of severe obesity (BMI >95th percentile on Hoover-Fong BMI charts) [Hoover-Fong et al, 2008].14
- Known closure of long bone growth plates (cessation of height growth).
- Body weight <7 kg or >30 kg.
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 |
|---|---|---|
| ReciferceptRecifercept | Biological | High Dose, Low Dose, Medium Dose, PK Phase 2 Formulation, PK Phase 3 Formulation |
Primary outcome
Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs)
Time frame: The first dose up to 28 to 35 days after the last dose of study intervention (13 months)
Treatment-related AE was any untoward medical occurrence attributed to study intervention in a participant who received study intervention. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AE is defined as an AE with onset date occurring during the on-treatment period. Relatedness to recifercept was assessed by the investigator (Yes/No).
Least Square Mean of Change From Baseline Height Growth at Month 3, Month 6, Month 9, and Month 12
Time frame: Baseline, Month 3, Month 6, Month 9, and Month 12
Height growth was defined as the ratio of observed change from baseline in standing height to the expected change from baseline in the reference population.
21 secondary outcomes
Change From Baseline in Pulse Rate at Month 3, Month 6, Month 9, and Month 12
Time frame: Baseline, Month 3, Month 6, Month 9, and Month 12
Change From Baseline in Respiratory Rate at Month 3, Month 6, Month 9, and Month 12
Time frame: Baseline, Month 3, Month 6, Month 9, and Month 12
Change From Baseline in Blood Pressure at Month 3, Month 6, Month 9, and Month 12
Time frame: Baseline, Month 3, Month 6, Month 9, and Month 12
Change From Baseline in Temperature at Month 3, Month 6, Month 9, and Month 12
Time frame: Baseline, Month 3, Month 6, Month 9, and Month 12
Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12
Time frame: Month 3, Month 6, Month 9, and Month 12
Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)
Time frame: Baseline to Month 12
Pre-Dose Serum Concentration (Ctrough) of Recifercept
Time frame: Pre-dose on Day(s) 4, 8, 15, 29, 61, 91, 183, 273, 365
Number of Participants With Positive Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) of Recifercept
Time frame: The first dose up to 28 to 35 days after the last dose of study intervention (13 months)
Change From Baseline in Sitting/Standing Height Ratio at Month 3, Month 6, Month 9, and Month 12
Time frame: Baseline, Month 3, Month 6, Month 9, and Month 12
Least Square Mean of Change From Baseline Arm Span to Standing Height/Length Difference at Month 3, Month 6, Month 9, and Month 12
Time frame: Baseline, Month 3, Month 6, Month 9, and Month 12
Change From Baseline in Knee Height : Lower Segment Ratio at Month 3, Month 6, Month 9, and Month 12
Time frame: Baseline, Month 3, Month 6, Month 9, and Month 12
Change From Baseline in Occipito-Frontal Circumference at Month 3, Month 6, Month 9, and Month 12
Time frame: Baseline, Month 3, Month 6, Month 9, and Month 12
Change From Baseline in Occipito-Frontal to Occipito-Mid-Face Ratio at Month 3, Month 6, Month 9, and Month 12
Time frame: Baseline, Month 3, Month 6, Month 9, and Month 12
Change From Baseline in Height Standard Deviation Score (Z-Score) at Month 3, Month 6, Month 9, and Month 12
Time frame: Baseline, Month 3, Month 6, Month 9, and Month 12
Change From Baseline in Fixed Flexion Angles at Elbow at Month 3, Month 6, Month 9, and Month 12
Time frame: Baseline, Month 3, Month 6, Month 9, and Month 12
Change From Baseline in Body Mass Index (BMI) at Month 3, Month 6, Month 9, and Month 12
Time frame: Baseline, Month 3, Month 6, Month 9, and Month 12
Change From Baseline in Waist : Chest Circumference Ratio at Month 9 and Month 12
Time frame: Baseline, Month 9, and Month 12
Change From Baseline in Apnea-Hypopnea Index (AHI) at Month 12
Time frame: Baseline and Month 12
Change From Baseline in Desaturation Index at Month 12
Time frame: Baseline and Month 12
Change From Baseline in Polysomnography Other Parameters at Month 12
Time frame: Baseline and Month 12
Change From Baseline in SaO2 Nadir at Month 12
Time frame: Baseline and Month 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38685585Qiao W, Boucher M, Slade A, Dawra VK. Natural disease course modeling of achondroplasia to evaluate the efficacy of recifercept in the absence of a placebo control arm in phase II study. CPT Pharmacometrics Syst Pharmacol. 2024 Jul;13(7):1103-1116. doi: 10.1002/psp4.13143. Epub 2024 Apr 29.
- 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
16 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Recifercept in people with Achondroplasia, run by Pfizer at 16 sites in 8 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 6 inclusion and 16 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 15 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in United States, Australia, Belgium, Japan, Denmark and 3 more countries. 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 15 Feb 2024). 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 Treatment Emergent Treatment-Related Adverse Events (AEs) (time frame: The first dose up to 28 to 35 days after the last dose of study intervention (13 months)). The study lists 2 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 NCT04638153, 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 15 Feb 2024.