Trial · NCT03549871
A Study of Fitusiran in Severe Hemophilia A and B Patients Previously Receiving Factor or Bypassing Agent Prophylaxis
NCT03549871, Phase 3, Completed, Genzyme, a Sanofi Company; results first posted 2023-02-06
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. A Study of Fitusiran in Severe Hemophilia A and B Patients Previously Receiving Factor or Bypassing Agent Prophylaxis. Trials, record NCT03549871. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT03549871
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- A Study of Fitusiran in Severe Hemophilia A and B Patients Previously Receiving Factor or Bypassing Agent Prophylaxis
- NCT number
- NCT03549871
- Status
- Completed
- Phases
- Phase 3
- Enrollment
- 80 participants, actual
- Lead sponsor
- Genzyme, a Sanofi Company
- Conditions
- Hemophilia
- Interventions
- Fitusiran, BPA prophylaxis, Factor (FVIII or FIX) prophylaxis
- First posted
- 2018-06-08
- Last updated
- 2023-02-06
- Other registries' IDs
- eudract:2016-004087-19
- Results first posted
- 2023-02-06
Source ClinicalTrials.gov
Registered outcomes15
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Estimated Annualized Bleeding Rate (ABR) | Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest | Bleeding episodes (BE): any occurrence of hemorrhage might require administration of factor/BPA. BE start time: time at which 1st BE symptoms develop; bleeding/any symptoms at same location occurred within 72 hours of last injection used to treat BE at that location was considered part of original BE and counted as 1 BE towards ABR. Bleeding began after 72 hours of last injection at that location was considered as a new event. ABR = total number of qualifying BE/total number of days in the respective period\*365.25. Estimated data were derived by using repeated measures negative binomial (NB) regression model. |
| Primary | Observed Annualized Bleeding Rate (ABR) | Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest | A bleeding episode (BE): any occurrence of hemorrhage might require administration of factor/BPA. BE start time: time at which 1st BE symptoms develop; bleeding/any symptoms at same location that occurred within 72 hours of last injection used to treat BE at that location was considered a part of original BE and counted as 1 BE towards ABR. Any bleeding that began after 72 hours of last injection at that location was considered as a new event. ABR = total number of qualifying BE/number of days in the respective period \*365.25. |
| Secondary | Estimated Annualized Spontaneous Bleeding Rate | Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest | BE: any occurrence of hemorrhage that might require administration of factor/BPA infusion. BE start time: time at which 1st BE symptoms develop; bleeding/any symptoms at same location that occurred within 72 hours of last injection used to treat BE at that location was considered part of original BE and counted as 1 BE towards ABR. Bleeding began after 72 hours of last injection at that location was considered as a new event. Spontaneous BE: BE occurrence for no apparent/known reason, particularly into joints, muscles, and soft tissues. ABR = total number of qualifying BE/number of days in respective period \*365.25. Estimated data was derived using repeated measures NB regression model. |
| Secondary | Observed Annualized Spontaneous Bleeding Rate | Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest | BE: any occurrence of hemorrhage that might require administration of factor/BPA. BE start time: time at which 1st BE symptoms develop; bleeding/any symptoms at same location that occurred within 72 hours of last injection used to treat BE at that location was considered part of original BE and was counted as 1 BE towards ABR. Bleeding began after 72 hours from last injection at that location was considered as a new event. Spontaneous BE: bleeding event occurred for no apparent or known reason, particularly into joints, muscles and soft tissues. ABR = total number of qualifying BE/number of days in respective period \*365.25. |
| Secondary | Estimated Annualized Joint Bleeding Rate | Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest | BE: any hemorrhage that required administration of factor/BPA. BE start time: time at which 1st BE symptoms develop; bleeding/any symptoms at same location that occurred within 72 hours of last injection to treat BE at that location was considered part of original BE; counted as 1 BE towards ABR. Bleeding after 72 hours from last injection at that location was considered as a new event. Joint BE: characterized by unusual sensation in joint ("aura") + increasing swelling/warmth over joint skin, increasing pain/progressive loss of range of motion/difficulty in limb use compared to Baseline. ABR = total number of qualifying BE/number of days in respective period \*365.25. Estimated data were derived by using repeated measures NB regression model. |
| Secondary | Observed Annualized Joint Bleeding Rate | Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest | BE: any occurrence of hemorrhage that might require administration of factor/BPA. BE start time: time at which 1st BE symptoms develop; bleeding/any symptoms at same location that occurred within 72 hours of last injection used to treat BE at that location was considered part of original BE and counted as 1 BE towards ABR. Bleeding began after 72 hours from last injection at that location was considered as a new event. Joint BE: characterized by unusual sensation in joint (aura) increasing swelling/warmth over joint skin, increasing pain or progressive loss of range of motion/difficulty in limb use compared to Baseline. ABR = total number of joint BE/number of days in respective period\*365.25. |
| Secondary | Change in Haemophilia Quality of Life Questionnaire for Adults (Haem-A-QOL) Physical Health Score in the Fitusiran Treatment Period and the Factor or BPA Prophylaxis Period | Month -6 of Factor or BPA prophylaxis period (Baseline), Day 1 (Month 1) and Month 7 of fitusiran treatment period | Haem-A-QoL: participant-reported questionnaire for adults aged \>=17 years with hemophilia and comprised of 46 items covering 10 domains. Physical health domain (PHD) is assessed with 5 items rated on 5-point Likert scale: never, rarely, sometimes, often or all the time. Raw score for PHD were transformed to scale ranged from 0 to 100, where lower scores = better physical health. Least square (LS) mean and 95% confidence interval (CI) by mixed model for repeated measure (MMRM) analysis with robust sandwich covariance matrix: change from Month -6 to Day 1 and to Month 7 as response variable; period (factor/BPA prophylaxis \& fitusiran treatment) \& Baseline score (Month -6) as fixed effects. |
| Secondary | Change in Haemophilia Quality of Life Questionnaire for Adults Total Score in the Fitusiran Treatment Period and the Factor or BPA Prophylaxis Period | Month -6 of Factor or BPA prophylaxis period (Baseline), Day 1 (Month 1) and Month 7 of fitusiran treatment period | Haem-A-QoL: questionnaire for adults aged \>= 17 years with hemophilia; and comprised of 46 items covering 10 domains: physical health, feelings, view of yourself, sports and leisure, work and school, dealing with hemophilia, treatment, future, family planning, partnership and sexuality. Items were rated on 5-point Likert scale: never, rarely, sometimes, often or all time. Domain raw score was transformed to scale ranged from 0 to 100, where lower scores=better health. LS mean \& 95% CI by MMRM analysis with robust sandwich covariance matrix: change from Month -6 to Day 1 and to Month 7 as response variable; period (factor/BPA prophylaxis \& fitusiran treatment) \& Baseline score (Month -6) as fixed effects. |
| Secondary | Estimated Annualized Bleeding Rate in the Fitusiran Onset Period | Day 1 up to Day 28 or up to the last day of bleeding follow up (any day up to Day 28), whichever was earliest | BE: any occurrence of hemorrhage that might require administration of factor/BPA. BE start time: time at which 1st BE symptoms develop; bleeding/any symptoms at same location that occurred within 72 hours of last injection used to treat BE at that location was considered part of original BE and was counted as 1 BE towards ABR. Bleeding began after 72 hours from last injection at that location was considered as new event. Estimated ABR and 95% CI was derived by using repeated measures NB regression model with logarithm of duration (years) that each participant spends in 1-Month fitusiran onset period matching BE data being analyzed as offset variable. ABR = total number of qualifying BE/number of days in respective period \*365.25. |
| Secondary | Observed Annualized Bleeding Rate in the Fitusiran Onset Period | Day 1 up to Day 28 or up to the last day of bleeding follow up (any day up to Day 28), whichever was earliest | BE: any occurrence of hemorrhage that might require administration of factor/BPA. BE start time: time at which 1st BE symptoms develop; bleeding/any symptoms at same location that occurred within 72 hours of last injection used to treat BE at that location was considered a part of original BE and was counted as one BE towards ABR. Bleeding began after 72 hours from last injection at that location was considered as a new event. ABR= total number of qualifying BE/number of days in the 1-month onset period \*365.25. Analysis was based on on-treatment strategy which included all treated bleeding events in 1-month onset period and excluded any bleeding events in period of intercurrent events. |
1 to 10 of 15Source ClinicalTrials.gov
See all 15 registered outcomesOutcomes15
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Estimated Annualized Bleeding Rate (ABR) | Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest | Analysis was performed on efficacy analysis set 1 (EAS1) which included participants who received factor/BPA prophylaxis and any dose of fitusiran before dose resumption. Data collection and analysis of combined population of Cohort A and B for each period was planned and performed for this outcome measure. | episodes per participant per year | NUMBER |
| PRIMARY | Observed Annualized Bleeding Rate (ABR) | Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest | Analysis was performed on EAS1 population. Data collection and analysis of combined population of Cohort A and B for each period was planned and performed for this outcome measure. | episodes per participant per year | MEAN |
| SECONDARY | Estimated Annualized Spontaneous Bleeding Rate | Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest | Analysis was performed on EAS 1 population. Data collection and analysis of combined population of Cohort A and B for each period was planned and performed for this outcome measure. | episodes per participant per year | NUMBER |
| SECONDARY | Observed Annualized Spontaneous Bleeding Rate | Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest | Analysis was performed on EAS 1 population. Data collection and analysis of combined population of Cohort A and B for each period was planned and performed for this outcome measure. | episodes per participant per year | MEAN |
| SECONDARY | Estimated Annualized Joint Bleeding Rate | Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest | Analysis was performed on EAS 1 population. Data collection and analysis of combined population of Cohort A and B for each period was planned and performed for this outcome measure. | episodes per participant per year | NUMBER |
| SECONDARY | Observed Annualized Joint Bleeding Rate | Factor/BPA prophylaxis period: Day -168 to Day -1 or up to last day of bleeding follow up (any day up to Day -1); 6-month fitusiran efficacy period: Day 29 to Day 190 or up to last day of bleeding follow up (any day up to Day 190), whichever was earliest | Analysis was performed on EAS 1 population. Data collection and analysis of combined population of Cohort A and B for each period was planned and performed for this outcome measure. | episodes per participant per year | MEAN |
| SECONDARY | Change in Haemophilia Quality of Life Questionnaire for Adults (Haem-A-QOL) Physical Health Score in the Fitusiran Treatment Period and the Factor or BPA Prophylaxis Period | Month -6 of Factor or BPA prophylaxis period (Baseline), Day 1 (Month 1) and Month 7 of fitusiran treatment period | Analysis was performed on EAS 1 population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure. Data collection and analysis of combined population of Cohort A and B for each period was planned and performed for this outcome measure. | score on a scale | LEAST_SQUARES_MEAN |
| SECONDARY | Change in Haemophilia Quality of Life Questionnaire for Adults Total Score in the Fitusiran Treatment Period and the Factor or BPA Prophylaxis Period | Month -6 of Factor or BPA prophylaxis period (Baseline), Day 1 (Month 1) and Month 7 of fitusiran treatment period | Analysis was performed on EAS1 population. Here, 'overall number of participants analyzed = participants with available data for this outcome measure. Data collection and analysis of combined population of Cohort A and B for each period was planned and performed for this outcome measure. | score on a scale | LEAST_SQUARES_MEAN |
| SECONDARY | Estimated Annualized Bleeding Rate in the Fitusiran Onset Period | Day 1 up to Day 28 or up to the last day of bleeding follow up (any day up to Day 28), whichever was earliest | Analysis was performed on EAS 1 population. Data collection and analysis of combined population of Cohort A and B for fitusiran 1-month onset period was planned and performed for this outcome measure. | episodes per participant per year | NUMBER |
| SECONDARY | Observed Annualized Bleeding Rate in the Fitusiran Onset Period | Day 1 up to Day 28 or up to the last day of bleeding follow up (any day up to Day 28), whichever was earliest | Analysis was performed on EAS 1 population. Data collection and analysis of combined population of Cohort A and B for fitusiran 1-month onset period was planned and performed for this outcome measure. | episodes per participant per year | MEAN |
1 to 10 of 15Source ClinicalTrials.gov
See all 15 outcomesResults by group28
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Estimated Annualized Bleeding Rate (ABR) | Overall Factor/BPA Prophylaxis Period | 7.482 | 95% Confidence Interval 5.520 to 10.141 | episodes per participant per year | |
| Estimated Annualized Bleeding Rate (ABR) | Overall Fitusiran 80 mg Efficacy Period | 2.908 | 95% Confidence Interval 1.727 to 4.898 | episodes per participant per year | |
| Observed Annualized Bleeding Rate (ABR) | Overall Factor/BPA Prophylaxis Period | 7.56 | Standard Deviation 9.49 | episodes per participant per year | |
| Observed Annualized Bleeding Rate (ABR) | Overall Fitusiran 80 mg Efficacy Period | 3.19 | Standard Deviation 7.75 | episodes per participant per year | |
| Estimated Annualized Spontaneous Bleeding Rate | Overall Factor/BPA Prophylaxis Period | 5.002 | 95% Confidence Interval 3.424 to 7.305 | episodes per participant per year | |
| Estimated Annualized Spontaneous Bleeding Rate | Overall Fitusiran 80 mg Efficacy Period | 2.222 | 95% Confidence Interval 1.190 to 4.152 | episodes per participant per year | |
| Observed Annualized Spontaneous Bleeding Rate | Overall Factor/BPA Prophylaxis Period | 5.09 | Standard Deviation 7.93 | episodes per participant per year | |
| Observed Annualized Spontaneous Bleeding Rate | Overall Fitusiran 80 mg Efficacy Period | 2.51 | Standard Deviation 7.33 | episodes per participant per year | |
| Estimated Annualized Joint Bleeding Rate | Overall Factor/BPA Prophylaxis Period | 5.282 | 95% Confidence Interval 3.647 to 7.651 | episodes per participant per year | |
| Estimated Annualized Joint Bleeding Rate | Overall Fitusiran 80 mg Efficacy Period | 2.564 | 95% Confidence Interval 1.440 to 4.566 | episodes per participant per year |
1 to 10 of 28Source ClinicalTrials.gov
See all 28 results by groupParticipant flow24
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Factor/BPA Prophylaxis: Day -168 to -1 | STARTED | Cohort A: Inhibitor | 30 | |
| Factor/BPA Prophylaxis: Day -168 to -1 | STARTED | Cohort B: Non-inhibitor | 50 | |
| Factor/BPA Prophylaxis: Day -168 to -1 | Started Directly With Fitusiran | Cohort A: Inhibitor | 2 | |
| Factor/BPA Prophylaxis: Day -168 to -1 | Started Directly With Fitusiran | Cohort B: Non-inhibitor | 0 | |
| Factor/BPA Prophylaxis: Day -168 to -1 | Started With Factor or BPA Prophylaxis | Cohort A: Inhibitor | 28 | |
| Factor/BPA Prophylaxis: Day -168 to -1 | Started With Factor or BPA Prophylaxis | Cohort B: Non-inhibitor | 50 | |
| Factor/BPA Prophylaxis: Day -168 to -1 | COMPLETED | Cohort A: Inhibitor | 23 | |
| Factor/BPA Prophylaxis: Day -168 to -1 | COMPLETED | Cohort B: Non-inhibitor | 46 | |
| Factor/BPA Prophylaxis: Day -168 to -1 | NOT COMPLETED | Cohort A: Inhibitor | 7 | |
| Factor/BPA Prophylaxis: Day -168 to -1 | NOT COMPLETED | Cohort B: Non-inhibitor | 4 |
1 to 10 of 24Source ClinicalTrials.gov
See all 24 participant flowAdverse events424
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Arthropod Bite | Injury, poisoning and procedural complications | Cohort A: SAS 1 - BPA Prophylaxis | 1 | 19 | 1 |
| other | Arthropod Bite | Injury, poisoning and procedural complications | Cohort A: SAS 1 - Fitusiran 80 mg QM | 1 | 21 | 1 |
| other | Arthropod Bite | Injury, poisoning and procedural complications | Cohort B: SAS 1 - Factor Prophylaxis | 0 | 46 | 0 |
| other | Arthropod Bite | Injury, poisoning and procedural complications | Cohort B: SAS 1 - Fitusiran 80 mg QM | 0 | 46 | 0 |
| other | Arthropod Bite | Injury, poisoning and procedural complications | Overall: SAS 1 - Factor/BPA Prophylaxis | 1 | 65 | 1 |
| other | Arthropod Bite | Injury, poisoning and procedural complications | Overall: SAS 1 - Fitusiran 80 mg QM | 1 | 67 | 1 |
| other | Arthropod Bite | Injury, poisoning and procedural complications | Cohort A: SAS 2 - BPA Prophylaxis | 0 | 2 | 0 |
| other | Arthropod Bite | Injury, poisoning and procedural complications | Cohort A: SAS 2 - Fitusiran 50 mg Q2M | 0 | 2 | 0 |
| other | Buttock Injury | Injury, poisoning and procedural complications | Cohort A: SAS 1 - BPA Prophylaxis | 1 | 19 | 1 |
| other | Buttock Injury | Injury, poisoning and procedural complications | Cohort A: SAS 1 - Fitusiran 80 mg QM | 0 | 21 | 0 |
1 to 10 of 424Source ClinicalTrials.gov
See all 424 adverse eventsAdverse event totals24
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Cohort A: SAS 1 - BPA Prophylaxis | 0 | 19 |
| Total, all-cause mortality | Cohort A: SAS 1 - Fitusiran 80 mg QM | 0 | 21 |
| Total, all-cause mortality | Cohort B: SAS 1 - Factor Prophylaxis | 0 | 46 |
| Total, all-cause mortality | Cohort B: SAS 1 - Fitusiran 80 mg QM | 0 | 46 |
| Total, all-cause mortality | Overall: SAS 1 - Factor/BPA Prophylaxis | 0 | 65 |
| Total, all-cause mortality | Overall: SAS 1 - Fitusiran 80 mg QM | 0 | 67 |
| Total, all-cause mortality | Cohort A: SAS 2 - BPA Prophylaxis | 0 | 2 |
| Total, all-cause mortality | Cohort A: SAS 2 - Fitusiran 50 mg Q2M | 0 | 2 |
| Total, other adverse events | Cohort A: SAS 1 - BPA Prophylaxis | 10 | 19 |
| Total, other adverse events | Cohort A: SAS 1 - Fitusiran 80 mg QM | 13 | 21 |
1 to 10 of 24Source ClinicalTrials.gov
See all 24 adverse event totalsPapers1
The papers the trial lists on ClinicalTrials.gov.
| PMID | Listed as |
|---|---|
| 38452197 | DERIVED |
Source PubMed
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons0
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
None in this release.
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
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