Hemophilia APhase 1/2NCT02554773
An Open-label Extension Study of an Investigational Drug, Fitusiran, in Patients With Moderate or Severe Hemophilia A or B
A Phase 1/2 study testing Fitusiran (SAR439774) in people with Hemophilia A and Hemophilia B, run by Genzyme, a Sanofi Company at 12 sites in 5 countries.
Trial summary
Primary Objective: To evaluate the long-term safety and tolerability of fitusiran in male patients with moderate or severe hemophilia A or B Secondary Objectives: To investigate the long-term efficacy of fitusiran To characterize the safety and efficacy of concomitantly administered Factor VIII (FVIII), Factor IX… Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Hemophilia A, Hemophilia B
- What is being tested?
- Fitusiran (SAR439774)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 12 sitesin 5 countries
- Study dates
- 18 Sep 2015to 21 Mar 2023
- Phase
- Phase 1/2
- 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 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Completed and tolerated study drug dosing in study TDR14767 (ALN-AT3SC-001)
- Male aged ≥18 years
- Moderate or severe, clinically stable hemophilia A or B as evidenced by a laboratory FVIII or FIX level ≤5% at screening. Patients with a FVIII or FIX level >5% at screening will be eligible on provision of a historic laboratory report indicating a trough level ≤5%
- Willing and able to comply with the study requirements and provide written informed consent
Who cannot join
- Clinically significant liver disease
- Patients known to be human immunodeficiency virus seropositive and have a CD4 count <200 cells/μL
- History of venous thromboembolism
- Current serious mental illness that, in the judgment of the Investigator, may compromise patient safety, ability to participate in all study assessments, or study integrity
- Clinically relevant history or presence of cardiovascular, respiratory, gastrointestinal, renal, neurological, inflammatory, or other diseases that, in the judgment of the Investigator, precludes study participation
Trial locations and contacts
12 sites in 5 countries.
12 sites in 5 countries
United Kingdom5 sites
Clinical Trial Site
Basingstoke
Clinical Trial Site
Glasgow
Clinical Trial Site
London, NW3 2QG
Clinical Trial Site
London, SW17 0QT
Clinical Trial Site
Truro
United States2 sites
Clinical Trial Site
Ann Arbor, Michigan, 48109
Clinical Trial Site
Pittsburgh, Pennsylvania
About this study
Official title: An Open-label Extension Study of Subcutaneously Administered Fitusiran in Patients With Moderate or Severe Hemophilia A or B Who Have Participated in a Previous Clinical Study With Fitusiran
Primary Objective:
To evaluate the long-term safety and tolerability of fitusiran in male patients with moderate or severe hemophilia A or B
Secondary Objectives:
- To investigate the long-term efficacy of fitusiran
- To characterize the safety and efficacy of concomitantly administered Factor VIII (FVIII), Factor IX (FIX) or bypassing agents (BPA) and fitusiran for treatment of bleeding episodes
- To assess changes in health-related quality of life (QOL) over time
- To characterize antithrombin (AT) reduction and thrombin generation (TG) increase
- To characterize the pharmacokinetics (PK) of fitusiran
Read the detailed description
It is anticipated that patients in this study will receive treatment with open label fitusiran for approximately 7 years or until fitusiran becomes commercially available, whichever occurs first.
- Conditions
- Hemophilia A, Hemophilia B
- Being tested
- Fitusiran (SAR439774)
- Keywords
- Hemophilia, RNAi therapeutic
- Medical subject headings
- Hemophilia A, Hemophilia B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fitusiran (SAR439774)Drug
Pharmaceutical form: solution for injection Route of administration : subcutaneous (sc)
| Study group | Role | What they receive |
|---|---|---|
| Fitusiran | Experimental | Patients will be administered subcutaneous (SC) fitusiran once monthly or every 2 months according to the dose selection rules defined in protocol. Receives: Drug: Fitusiran (SAR439774) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs)
An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An SAE is any untoward medical occurrence that results: death or life-threatening or inpatient hospitalization or prolongation of existing hospitalization or persistent or significant disability or congenital anomaly or medically important event. All AEs collected in LTE14762 were considered TEAE because all participants received dose in the parent study. AEs of special interest (AESI) are alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevations >3× upper limit of normal (ULN) or suspected or confirmed thromboembolic events or severe or serious injection site reactions or systemic injection associated reactions or cholecystitis or cholelithiasis.
Measured: From first dose of study drug (Day 1) up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)
Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology
Blood samples were collected to determine the hematology laboratory significant abnormalities. Here, DFB = decrease from baseline, NB = non-black, and B = black.
Measured: From first dose of study drug (Day 1) up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)
Number of Participants With Potentially Clinically Significant Abnormality: Clinical Chemistry
Blood samples were collected to determine the clinical chemistry laboratory abnormalities. Here, mmol/L = millimoles per liter, LLN = lower limit of normal, mg/L = milligram per liter, umol/L = micromoles per liter, mL/min = milliliter per minute, m^2 = meter square, CB = conjugated bilirubin, and DB = direct bilirubin.
Measured: From first dose of study drug (Day 1) up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)
Number of Participants With Potentially Clinically Significant Abnormality: Urinalysis
Urine samples collected to determine the significant abnormalities in urine.
Measured: From first dose of study drug (Day 1) up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)
Number of Participants With Potentially Clinically Significant Abnormality: Vital Signs
Participants vital signs were examined to determine the abnormalities. Vital signs included weight, supine systolic blood pressure (SSBP) and supine diastolic blood pressure (SDBP). Here, mmHg = millimeter of mercury, and IFB = increase from baseline.
Measured: From first dose of study drug (Day 1) up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)
Number of Participants With Potentially Clinically Significant Abnormality: Electrocardiogram (ECG)
Standard 12-lead ECGs were recorded after at least 15 minutes in the supine position using an electrocardiographic device. The following were assessed: heart rate, rhythm, interval between the peaks of successive QRS complexes (RR), interval from the beginning of the P wave until the beginning of the QRS complex (PR), interval from start of the Q wave to the end of the S wave (QRS), interval between the start of the Q wave and the end of the T wave (QT), QT interval corrected for heart rate (QTc) automatic correction evaluation, QRS axis, left ventricular hypertrophy criteria, right ventricular hypertrophy criteria, repolarization charges, and overall cardiac impression for each participant. Here, msec = milliseconds.
Measured: From first dose of study drug (Day 1) up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)
Number of Participants With Potentially Clinically Significant Abnormality: Physical Examination
Physical examination included, at a minimum, an assessment of the participant's general appearance; skin; head, eyes, ears, nose, and throat; examinations of lymph nodes, abdomen, extremities/joints, neurological and mental status; heart and respiratory auscultation; peripheral arterial pulse; and pupil, knee, achilles, and plantar reflexes.
Measured: From first dose of study drug (Day 1) up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)
Secondary outcomes (19)
Annualized Bleeding Rate (ABR) During the Efficacy Period
The ABR was annualized for each participant using the following formula: ABR = total number of bleeding events/total number of days in the respective period x 365.25. The efficacy period was defined as treatment Day 29 to earlier of end of study date before the dose pause or the last fitusiran administration date before the dose pause + 28 days, whichever comes first for original dose regimen (SAS 1) and the dose re-start Day 169 to the end of study visit for AT-based dose regimen (SAS 2).
Measured: From Day 29 up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)
Annualized Spontaneous Bleeding Rate During the Efficacy Period
A spontaneous bleeding episode was defined as a bleeding event that occurred for no apparent or known reason, particularly into the joints, muscles, and soft tissues. The efficacy period was defined as treatment Day 29 to earlier of end of study date before the dose pause or the last fitusiran administration date before the dose pause + 28 days, whichever comes first for original dose regimen (SAS 1) and the dose re-start Day 169 to the end of study visit for AT-based dose regimen (SAS 2).
Measured: From Day 29 up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)
Annualized Joint Bleeding Rate During the Efficacy Period
A joint bleeding episode was defined as an event that is characterized by an unusual sensation in the joint ("aura") in combination with 1) increasing swelling or warmth over the skin over the joint; 2) increasing pain; or 3) progressive loss of range of motion or difficulty in using the limb as compared with baseline. The efficacy period was defined as treatment Day 29 to earlier of end of study date before the dose pause or the last fitusiran administration date before the dose pause + 28 days, whichever comes first for original dose regimen (SAS 1) and the dose re-start Day 169 to the end of study visit for AT-based dose regimen (SAS 2).
Measured: From Day 29 up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)
Time Intervals Between Bleeding Events
Bleed-free duration was defined as the time interval between 2 protocol-defined treated bleeding events, excluding events that occurred during the intercurrent periods.
Measured: From Day 29 up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)
Annualized Weight-Adjusted Consumption of Coagulation Factor VIII (FVIII) and Coagulation Factor IX (FIX)
Number of coagulation factor injections per bleed was determined. IU= international units, and kg= kilogram.
Measured: From Day 29 up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)
Annualized Weight-Adjusted Consumption of Bypassing Agent (BPA) of Recombinant Factor VIIa (rFVIIa)
Number of BPA injections per bleed was determined.
Measured: From Day 29 up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)
Annualized Weight-Adjusted Consumption of Bypassing Agent (BPA) of Activated Prothrombin Complex Concentrate (aPCC)
Number of BPA injections per bleed was determined.
Measured: From Day 29 up to end of the study, maximum of up to 76 months
Change From Baseline in EuroQoL 5-Dimension 5-level Questionnaire (EQ-5D-5L) Index and Visual Analog Scale (VAS) Scores at Month 24
The EQ-5D-5L is a standardized and disease-generic instrument for use as a measure of quality of life (QoL) outcome. The EQ-5D-5L consists of 2 parts: EQ-5D descriptive system and EQ VAS. The EQ-5D descriptive system included questions for each of following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The VAS recorded participant's self-rated health on a vertical 20-centimeter. VAS scale ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). The EQ-5D-5L questionnaire scores range from 0-100, where 0= worst self-perceived health and 100= best self-perceived health. Positive change from baseline indicates an improvement in QoL. Baseline refers to the last non-missing value on or before the first significant treatment in TDR14767(ALN-AT3SC-001) or LTE14762 study.
Measured: Baseline and Month 24
Change From Baseline in Hemophilia Quality of Life Questionnaire (Haem-A-QoL) Total Score and Physical Health Scores at Month 24
The Haem-A-QoL questionnaire is psychometrically tested QoL assessment instrument for participants with hemophilia and includes 46 items contributing to 10 QoL domains (physical health, feelings, view of yourself, sports and leisure, work and school, dealing with hemophilia, treatment, future, family planning, partnership and sexuality). Scoring for each item is based on a 5-point Likert scale (1= never, 2= rarely, 3= sometimes, 4= often, and 5= all the time), and the physical health and total transformed scores range from 0 to 100. Higher scores indicated greater impairment. Baseline refers to the last non-missing value on or before the first significant treatment in TDR14767(ALN-AT3SC-001) or LTE14762 study.
Measured: Baseline and Month 24
Antithrombin Activity Level at the End of Treatment Regimen
The AT activity level was analyzed up to end of treatment regimen. The baseline under the original dose and regimen was the last non-missing assessment before the first significant dose.
Measured: From Day 29 up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)
Thrombin Generation at the End of Treatment Regimen
The TG data was analyzed by CoagScope and assay performed using calibrated automated thrombogram method. The baseline under the original dose and regimen was the last non-missing assessment before the first significant dose.
Measured: From Day 29 up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)
Maximum Observed Concentration (Cmax) of Fitusiran
Cmax was defined as maximum plasma concentration observed. The non-compartmental Pharmacokinetic (PK) analysis was performed.
Measured: Pre-dose and 0.5, 2, 4, 8 and 24 hours post-dose on Day 1, and Months 12 and 24
Time to Reach the Maximum Concentration (Tmax) of Fitusiran
tmax was defined as time to reach Cmax. The non-compartmental PK analysis was performed.
Measured: Pre-dose and 0.5, 2, 4, 8 and 24 hours post-dose on Day 1, and Months 12 and 24
Area Under the Concentration Versus Time Curve From Time 0 to the Real Time (AUClast) of Fitusiran
AUClast was defined as area under the concentration versus time curve from time 0 to the last measurable concentration. The non-compartmental PK analysis was performed.
Measured: Pre-dose and 0.5, 2, 4, 8 and 24 hours post-dose on Day 1, and Months 12 and 24
Area Under the Concentration Versus Time Curve Extrapolated to Infinity (AUCinf) of Fitusiran
AUCinf was defined as area under the concentration versus time curve extrapolated to infinity. The non-compartmental PK analysis was performed.
Measured: Pre-dose and 0.5, 2, 4, 8 and 24 hours post-dose on Day 1 and Month 12
Terminal Half-Life (t1/2z) of Fitusiran
t1/2z associated with the terminal slope (λz) determined according to the following equation: t1/2z = 0.693/λz; where, λz is the slope of the regression line of the terminal phase of the plasma concentration versus time curve, in semi-logarithmic scale. The non-compartmental PK analysis was performed.
Measured: Pre-dose and 0.5, 2, 4, 8 and 24 hours post-dose on Day 1 and Month 12
Apparent Total Body Clearance (CL/F) of Fitusiran
CL/F was defined as apparent clearance of study drug from the body. The non-compartmental PK analysis was performed.
Measured: Pre-dose and 0.5, 2, 4, 8 and 24 hours post-dose on Day 1 and Month 12
Apparent Volume of Distribution at the Steady State After Single Extravascular Dose (Vss/F) of Fitusiran
Vss/F was defined as apparent volume of distribution of study drug at steady state concentration. The non-compartmental PK analysis was performed.
Measured: Pre-dose and 0.5, 2, 4, 8 and 24 hours post-dose on Day 1 and Month 12
Recovery of Fraction of the Dose Excreted in Urine (fe) in 0-24 Hours After Fitusiran Administration
fe was defined as the amount of fitusiran excreted in urine in 0-24 hour. The non-compartmental PK analysis was performed.
Measured: Postdose, 0 to 6 hours, 6 to 12 hours, 12 to 24 hours at Month 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2015 (estimated)
- Study start18 Sep 2015
- Primary completion21 Mar 2023
- Study completion21 Mar 2023
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 Hemophilia AStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genzyme, a Sanofi Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, MD, Study director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02554773
- Sponsor's protocol ID
- LTE14762
- Other IDs
- ALN-AT3SC-002, 2015-001395-21, U1111-1251-5204, 2015
- Status last verified
- Jun 2024
- First submitted
- 15 Sep 2015
- Last updated
- 5 Jun 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
Publications
Pipe SW, Lissitchkov T, Georgiev P, Mangles S, Hegemann I, Trinchero A, Chowdary P, Forbes A, Feng L, Menapace LA, Kichou S, Andersson S, Demissie M, Ragni MV. Long-term safety and efficacy of fitusiran prophylaxis, and perioperative management, in people with hemophilia A or B. Blood Adv. 2025 Mar 11;9(5):1147-1158. doi: 10.1182/bloodadvances.2024013900.
PubMed 39642315
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label Extension Study of Subcutaneously Administered Fitusiran in Patients With Moderate or Severe Hemophilia A or B Who Have Participated in a Previous Clinical Study With Fitusiran
- ClinicalTrials.gov ID
- NCT02554773
- Acronym / sponsor ID
- LTE14762
- Conditions
- Hemophilia A, Hemophilia B
- Keywords
- Hemophilia, RNAi therapeutic
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Genzyme, a Sanofi CompanyIndustry (pharma, biotech, devices)
- Study start
- 18 Sep 2015 (actual)
- Primary completion
- 21 Mar 2023 (actual)
- Study completion
- 21 Mar 2023 (actual)
- First posted
- 18 Sep 2015 (estimated)
- Results
- Posted 5 Jun 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary Objective:
To evaluate the long-term safety and tolerability of fitusiran in male patients with moderate or severe hemophilia A or B
Secondary Objectives:
- To investigate the long-term efficacy of fitusiran
- To characterize the safety and efficacy of concomitantly administered Factor VIII (FVIII), Factor IX (FIX) or bypassing agents (BPA) and fitusiran for treatment of bleeding episodes
- To assess changes in health-related quality of life (QOL) over time
- To characterize antithrombin (AT) reduction and thrombin generation (TG) increase
- To characterize the pharmacokinetics (PK) of fitusiran
Detailed description
It is anticipated that patients in this study will receive treatment with open label fitusiran for approximately 7 years or until fitusiran becomes commercially available, whichever occurs first.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Fitusiran | Experimental | Drug: Fitusiran (SAR439774)Patients will be administered subcutaneous (SC) fitusiran once monthly or every 2 months according to the dose selection rules defined in protocol. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Completed and tolerated study drug dosing in study TDR14767 (ALN-AT3SC-001)
- Male aged ≥18 years
- Moderate or severe, clinically stable hemophilia A or B as evidenced by a laboratory FVIII or FIX level ≤5% at screening. Patients with a FVIII or FIX level >5% at screening will be eligible on provision of a historic laboratory report indicating a trough level ≤5%
- Willing and able to comply with the study requirements and provide written informed consent
Key exclusion criteria (5 listed)
- Clinically significant liver disease
- Patients known to be human immunodeficiency virus seropositive and have a CD4 count <200 cells/μL
- History of venous thromboembolism
- Current serious mental illness that, in the judgment of the Investigator, may compromise patient safety, ability to participate in all study assessments, or study integrity
- Clinically relevant history or presence of cardiovascular, respiratory, gastrointestinal, renal, neurological, inflammatory, or other diseases that, in the judgment of the Investigator, precludes study participation
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 |
|---|---|---|
| Fitusiran (SAR439774)Pharmaceutical form: solution for injection Route of administration : subcutaneous (sc) | Drug | Fitusiran |
Primary outcome
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs)
Time frame: From first dose of study drug (Day 1) up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)
An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An SAE is any untoward medical occurrence that results: death or life-threatening or inpatient hospitalization or prolongation of existing hospitalization or persistent or significant disability or congenital anomaly or medically important event. All AEs collected in LTE14762 were considered TEAE because all participants received dose in the parent study. AEs of special interest (AESI) are alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevations >3× upper limit of normal (ULN) or suspected or confirmed thromboembolic events or severe or serious injection site reactions or systemic injection associated reactions or cholecystitis or cholelithiasis.
Number of Participants With Potentially Clinically Significant Abnormality (PCSA): Hematology
Time frame: From first dose of study drug (Day 1) up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)
Blood samples were collected to determine the hematology laboratory significant abnormalities. Here, DFB = decrease from baseline, NB = non-black, and B = black.
Number of Participants With Potentially Clinically Significant Abnormality: Clinical Chemistry
Time frame: From first dose of study drug (Day 1) up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)
Blood samples were collected to determine the clinical chemistry laboratory abnormalities. Here, mmol/L = millimoles per liter, LLN = lower limit of normal, mg/L = milligram per liter, umol/L = micromoles per liter, mL/min = milliliter per minute, m^2 = meter square, CB = conjugated bilirubin, and DB = direct bilirubin.
Number of Participants With Potentially Clinically Significant Abnormality: Urinalysis
Time frame: From first dose of study drug (Day 1) up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)
Urine samples collected to determine the significant abnormalities in urine.
Number of Participants With Potentially Clinically Significant Abnormality: Vital Signs
Time frame: From first dose of study drug (Day 1) up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)
Participants vital signs were examined to determine the abnormalities. Vital signs included weight, supine systolic blood pressure (SSBP) and supine diastolic blood pressure (SDBP). Here, mmHg = millimeter of mercury, and IFB = increase from baseline.
Number of Participants With Potentially Clinically Significant Abnormality: Electrocardiogram (ECG)
Time frame: From first dose of study drug (Day 1) up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)
Standard 12-lead ECGs were recorded after at least 15 minutes in the supine position using an electrocardiographic device. The following were assessed: heart rate, rhythm, interval between the peaks of successive QRS complexes (RR), interval from the beginning of the P wave until the beginning of the QRS complex (PR), interval from start of the Q wave to the end of the S wave (QRS), interval between the start of the Q wave and the end of the T wave (QT), QT interval corrected for heart rate (QTc) automatic correction evaluation, QRS axis, left ventricular hypertrophy criteria, right ventricular hypertrophy criteria, repolarization charges, and overall cardiac impression for each participant. Here, msec = milliseconds.
Number of Participants With Potentially Clinically Significant Abnormality: Physical Examination
Time frame: From first dose of study drug (Day 1) up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)
Physical examination included, at a minimum, an assessment of the participant's general appearance; skin; head, eyes, ears, nose, and throat; examinations of lymph nodes, abdomen, extremities/joints, neurological and mental status; heart and respiratory auscultation; peripheral arterial pulse; and pupil, knee, achilles, and plantar reflexes.
19 secondary outcomes
Annualized Bleeding Rate (ABR) During the Efficacy Period
Time frame: From Day 29 up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)
Annualized Spontaneous Bleeding Rate During the Efficacy Period
Time frame: From Day 29 up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)
Annualized Joint Bleeding Rate During the Efficacy Period
Time frame: From Day 29 up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)
Time Intervals Between Bleeding Events
Time frame: From Day 29 up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)
Annualized Weight-Adjusted Consumption of Coagulation Factor VIII (FVIII) and Coagulation Factor IX (FIX)
Time frame: From Day 29 up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)
Annualized Weight-Adjusted Consumption of Bypassing Agent (BPA) of Recombinant Factor VIIa (rFVIIa)
Time frame: From Day 29 up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)
Annualized Weight-Adjusted Consumption of Bypassing Agent (BPA) of Activated Prothrombin Complex Concentrate (aPCC)
Time frame: From Day 29 up to end of the study, maximum of up to 76 months
Change From Baseline in EuroQoL 5-Dimension 5-level Questionnaire (EQ-5D-5L) Index and Visual Analog Scale (VAS) Scores at Month 24
Time frame: Baseline and Month 24
Change From Baseline in Hemophilia Quality of Life Questionnaire (Haem-A-QoL) Total Score and Physical Health Scores at Month 24
Time frame: Baseline and Month 24
Antithrombin Activity Level at the End of Treatment Regimen
Time frame: From Day 29 up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)
Thrombin Generation at the End of Treatment Regimen
Time frame: From Day 29 up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)
Maximum Observed Concentration (Cmax) of Fitusiran
Time frame: Pre-dose and 0.5, 2, 4, 8 and 24 hours post-dose on Day 1, and Months 12 and 24
Time to Reach the Maximum Concentration (Tmax) of Fitusiran
Time frame: Pre-dose and 0.5, 2, 4, 8 and 24 hours post-dose on Day 1, and Months 12 and 24
Area Under the Concentration Versus Time Curve From Time 0 to the Real Time (AUClast) of Fitusiran
Time frame: Pre-dose and 0.5, 2, 4, 8 and 24 hours post-dose on Day 1, and Months 12 and 24
Area Under the Concentration Versus Time Curve Extrapolated to Infinity (AUCinf) of Fitusiran
Time frame: Pre-dose and 0.5, 2, 4, 8 and 24 hours post-dose on Day 1 and Month 12
Terminal Half-Life (t1/2z) of Fitusiran
Time frame: Pre-dose and 0.5, 2, 4, 8 and 24 hours post-dose on Day 1 and Month 12
Apparent Total Body Clearance (CL/F) of Fitusiran
Time frame: Pre-dose and 0.5, 2, 4, 8 and 24 hours post-dose on Day 1 and Month 12
Apparent Volume of Distribution at the Steady State After Single Extravascular Dose (Vss/F) of Fitusiran
Time frame: Pre-dose and 0.5, 2, 4, 8 and 24 hours post-dose on Day 1 and Month 12
Recovery of Fraction of the Dose Excreted in Urine (fe) in 0-24 Hours After Fitusiran Administration
Time frame: Postdose, 0 to 6 hours, 6 to 12 hours, 12 to 24 hours at Month 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39642315Pipe SW, Lissitchkov T, Georgiev P, Mangles S, Hegemann I, Trinchero A, Chowdary P, Forbes A, Feng L, Menapace LA, Kichou S, Andersson S, Demissie M, Ragni MV. Long-term safety and efficacy of fitusiran prophylaxis, and perioperative management, in people with hemophilia A or B. Blood Adv. 2025 Mar 11;9(5):1147-1158. doi: 10.1182/bloodadvances.2024013900.
- Individual participant dataSharing planned: Yes. Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
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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.
Clinical Sciences & Operations, MD study director
Sanofi
12 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Fitusiran (SAR439774) in people with Hemophilia A and Hemophilia B, run by Genzyme, a Sanofi Company at 12 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 4 inclusion and 5 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: finished, as of the sponsor's last update on 5 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United Kingdom, United States, Bulgaria, Russia, Switzerland. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 5 Jun 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 Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) (time frame: From first dose of study drug (Day 1) up to end of the study (SAS 1: up to 76 months and SAS 2: up to 40 months)). The study lists 7 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 NCT02554773, 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 5 Jun 2024.