An Open-label Extension Study of an Investigational Drug, Fitusiran, in Patients With Moderate or Severe Hemophilia A or B

Study Overview
=================
Brief 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 (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.

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

Conditions
-----------------
Hemophilia A, Hemophilia B

Intervention / Treatment
-----------------
* Drug: Fitusiran (SAR439774)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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>Patients will be administered subcutaneous (SC) fitusiran once monthly or every 2 months according to the dose selection rules defined in protocol. | Drug: Fitusiran (SAR439774)<br>* Pharmaceutical form: solution for injection Route of administration : subcutaneous (sc)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and AEs leading to study drug discontinuation | Incidence of treatment-emergent adverse events (AEs), serious adverse events (SAEs), and AEs leading to study drug discontinuation | Up to 7 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized bleed rate (ABR) |  | Up to 7 years | 
| Time intervals between bleeding episodes |  | Up to 7 years | 
| Weight-adjusted consumption of FVIII, FIX, or BPA | BPA Assessment of concomitantly administered factor VIII (FVIII), factor IX (FIX), or bypassing agents (BPA) and fitusiran for treatment of bleeding | Up to 7 years | 
| Changes in health-related quality of life (QOL) with long-term dosing of fitusiran | QOL assessed by an EQ-5D questionnaire and HAEM-A-QoL | Up to 7 years | 
| Pharmacokinetics (PK) of fitusiran: Cmax |  | Day 1, Month 12, Month 24 | 
| Pharmacokinetics (PK) of fitusiran: AUC |  | Day 1, Month 12, Month 24 | 
| Pharmacokinetics (PK) of fitusiran: t1/2 |  | Day 1, Month 12, Month 24 | 
| Pharmacokinetics (PK) of fitusiran: CL/F |  | Day 1, Month 12, Month 24 | 
| Pharmacokinetics (PK) of fitusiran: V/F |  | Day 1, Month 12, Month 24 | 
| The effect of fitusiran on plasma levels of antithrombin (AT) and thrombin generation (TG) |  | Up to 7 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hemophilia, RNAi therapeutic