Long-term Safety and Efficacy Study of Fitusiran in Patients With Hemophilia A or B, With or Without Inhibitory Antibodies to Factor VIII or IX

Study Overview
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Brief Summary
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Primary Objective: To characterize the long-term safety and tolerability of fitusiran Secondary Objectives: To characterize the efficacy and long-term efficacy of fitusiran as assessed by the frequency of: Bleeding episodes Spontaneous bleeding episodes Joint bleeding episodes To characterize the effects of fitusiran on health-related quality of life (HRQOL) measures in participants ≥17 years of age

Detailed Description
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The estimated total time on the study for a participant up to 90 months (including screening, treatment period and safety follow up period).

Official Title
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An Open-label, Long-term Safety and Efficacy Study of Fitusiran in Patients With Hemophilia A or B, With or Without Inhibitory Antibodies to Factor VIII or IX

Conditions
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Hemophilia

Intervention / Treatment
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* Drug: Fitusiran


Participation Criteria
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Eligibility Criteria
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Inclusion criteria : Participant must be at least 12 years of age inclusive, at the time of signing the informed consent Participants with severe hemophilia A or B who have completed a Phase 3 fitusiran clinical trial Male Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol. In countries where legal age of majority is above 18 years, a specific ICF must also be signed by the participant's legally authorized representative Exclusion criteria: Completion of a surgical procedure within 14 days prior to screening, or currently receiving additional factor concentrate or BPA infusion for postoperative hemostasis Current participation in immune tolerance induction treatment (ITI) Current use of factor concentrates or bypassing agents (BPAs) as regularly administered prophylaxis designed to prevent spontaneous bleeding episodes except for participants requiring factor concentrates or BPAs prophylaxis during the study dosing pause period Use of compounds other than factor concentrates or BPAs for hemophilia treatment Current or prior participation in a gene therapy trial Alanine aminotransferase (ALT) and/or Aspartate aminotransferase (AST) >1.5 × upper limit of normal reference range (ULN) for patients who are naïve to fitusiran at study start; ALT and/or AST > 5 x ULN for patients who were in the fitusiran arm in the parent study Additional exclusions for participants not currently participating in a fitusiran trial at the time of enrollment in the lower dose cohort: Clinically significant liver disease History of arterial or venous thromboembolism The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fitusiran<br>Participants will be administered fitusiran as a subcutaneous injection once monthly or every other month for up to 48 months post initiation of modified IMP dose/frequency or until fitusiran becomes commercially available, whichever comes first. | Drug: Fitusiran<br>* Pharmaceutical form:solution for injection Route of administration: subcutaneous<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment emergent adverse events (TEAEs) | The number of participants experiencing any TEAEs, serious TEAEs, discontinuation due to TEAEs and death will be reported | from study baseline (day 1) up to maximum 88 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized bleeding rate (ABR) | Annualized bleeding rate (ABR) in the treatment period | from first ever dose of fitusiran (day 1) up to maximum 78 months | 
| Annualized spontaneous bleeding rate | Annualized spontaneous bleeding rate in the treatment period | from first ever dose of fitusiran (day 1) up to maximum 78 months | 
| Annualized joint bleeding rate | Annualized joint bleeding rate in the treatment period | from first ever dose of fitusiran (day 1) up to maximum 78 months | 
| Changes in Haem-A-quality of life (QoL) score | Change in Haem A QoL physical health score and total score in the treatment period (in participants ≥17 years of age) from first ever dose of fitusiran (day 1) to month 48 | from first ever dose of fitusiran (day 1) up to maximum 78 months |