An Open-label, Single-arm Treatment Study to Investigate the Safety and Tolerability of Switching From Emicizumab to Fitusiran Prophylaxis in Male Participants Aged ≥12 Years of Age With Severe Hemophilia A, With or Without Inhibitors
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- Sanofi
- 入组人数
- 20
- 试验地点
- 4
- 主要终点
- Number of participants with Adverse events (AEs) during the fitusiran treatment
研究概览
简要总结
This is an exploratory, single group, Phase 4, study to assess treatment with fitusiran prophylaxis after switching from emicizumab prophylaxis.
This study aims to evaluate the safety and tolerability of switching to fitusiran after a transition period from the last dose of emicizumab. The study will be conducted in male participants with severe hemophilia A, with or without inhibitors, aged ≥12 years, who were previously receiving emicizumab prophylaxis.
Study details include:
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The study duration will be up to approximately 28 months:
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There will be an approximately 2-month screening period.
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There will be an approximately 2-month period before fitusiran treatment starts (pre-fitusiran treatment period)
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The fitusiran treatment duration will be up to 18-months (fitusiran treatment period)
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The antithrombin (AT) follow-up (FU) period will be approximately 6 months after the last dose of fitusiran (during which the AT activity level will be monitored at approximately monthly intervals following the final fitusiran dose until AT activity levels return to at least 60%).
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The study site visits are scheduled at monthly/ every 2 months intervals of 28 days (4 weeks) / 56 days (8 weeks), respectively, during the fitusiran treatment period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Male participants must be ≥12 years of age inclusive, at the time of signing the informed consent
- •Diagnosis of severe congenital hemophilia A (FVIII < 1%) as evidenced by a central laboratory measurement at screening or documented medical record evidence.
- •Inhibitor titer of ≥0.6 BU/mL at Screening, or
- •Inhibitor titer of <0.6 BU/mL at Screening with medical record evidence of 2 consecutive titers ≥0.6 BU/mL, or
- •Inhibitor titer of <0.6 BU/mL at Screening with medical record evidence of anamnestic response.
- •Participants who are currently on the full labeled dose of emicizumab prophylaxis, irrespective of inhibitor/non-inhibitor status.
- •Signed informed consent/assent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
排除标准
- •Participants are excluded from the study if any of the following criteria apply:
- •Known coexisting bleeding disorders
- •History of antiphospholipid antibody syndrome.
- •History of arterial or venous thromboembolism, atrial fibrillation, significant valvular disease, myocardial infarction, angina, transient ischemic attack, or stroke. Participants who have experienced thrombosis associated with indwelling venous access may be enrolled.
- •Presence of clinically significant liver disease
- •Current or prior participation in a fitusiran trial
- •Current or prior participation in a gene therapy trial
- •AT activity <60% at Screening, as determined by central laboratory measurement
- •Coexisting thrombophilic disorder - Hepatitis C virus antibody positive, except participants who have negative Hepatitis C viral load and no evidence of cirrhosis
- •Presence of acute hepatitis, ie, hepatitis A, hepatitis E.
- •Presence of acute or chronic hepatitis B infection
- •Known to be HIV positive with CD4 count <200 cells/μL.
- •Reduced renal function
- •The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
研究组 & 干预措施
fitusiran
The pre-fitusiran treatment period is defined as the transition period up to the first fitusiran administration. Participants will receive on demand or prophylactic treatment with intravenous clotting factor concentrates (IV CFCs) or bypassing agents (BPAs) from Month-2 until Day 1.
Fitusiran treatment period: Participants will receive subcutaneous (SC) fitusiran prophylaxis once every 2 months (Q2M) or once monthly (QM) from Day 1 until Month18.
Participants may receive IV antithrombin concentrate (ATIIIC) upon investigator's judgement.
AT FU period: Participants will be followed up until AT activity levels recover to at least 60% (per central laboratory).
In case of bleeding events participants will receive IV CFCs or BPAs. Participants may receive IV ATIIIC upon investigator's judgement.
干预措施: Fitusiran (SAR439774) (Drug)
fitusiran
The pre-fitusiran treatment period is defined as the transition period up to the first fitusiran administration. Participants will receive on demand or prophylactic treatment with intravenous clotting factor concentrates (IV CFCs) or bypassing agents (BPAs) from Month-2 until Day 1.
Fitusiran treatment period: Participants will receive subcutaneous (SC) fitusiran prophylaxis once every 2 months (Q2M) or once monthly (QM) from Day 1 until Month18.
Participants may receive IV antithrombin concentrate (ATIIIC) upon investigator's judgement.
AT FU period: Participants will be followed up until AT activity levels recover to at least 60% (per central laboratory).
In case of bleeding events participants will receive IV CFCs or BPAs. Participants may receive IV ATIIIC upon investigator's judgement.
干预措施: Clotting factor concentrates (CFC) or bypassing agents (BPA) (Biological)
fitusiran
The pre-fitusiran treatment period is defined as the transition period up to the first fitusiran administration. Participants will receive on demand or prophylactic treatment with intravenous clotting factor concentrates (IV CFCs) or bypassing agents (BPAs) from Month-2 until Day 1.
Fitusiran treatment period: Participants will receive subcutaneous (SC) fitusiran prophylaxis once every 2 months (Q2M) or once monthly (QM) from Day 1 until Month18.
Participants may receive IV antithrombin concentrate (ATIIIC) upon investigator's judgement.
AT FU period: Participants will be followed up until AT activity levels recover to at least 60% (per central laboratory).
In case of bleeding events participants will receive IV CFCs or BPAs. Participants may receive IV ATIIIC upon investigator's judgement.
干预措施: Antithrombin concentrate (ATIIIC) (Biological)
fitusiran
The pre-fitusiran treatment period is defined as the transition period up to the first fitusiran administration. Participants will receive on demand or prophylactic treatment with intravenous clotting factor concentrates (IV CFCs) or bypassing agents (BPAs) from Month-2 until Day 1.
Fitusiran treatment period: Participants will receive subcutaneous (SC) fitusiran prophylaxis once every 2 months (Q2M) or once monthly (QM) from Day 1 until Month18.
Participants may receive IV antithrombin concentrate (ATIIIC) upon investigator's judgement.
AT FU period: Participants will be followed up until AT activity levels recover to at least 60% (per central laboratory).
In case of bleeding events participants will receive IV CFCs or BPAs. Participants may receive IV ATIIIC upon investigator's judgement.
干预措施: Emicizumab (Biological)
结局指标
主要结局
Number of participants with Adverse events (AEs) during the fitusiran treatment
时间窗: From Day 1 up to Month 4
Incidence, severity, and seriousness, of AEs occurred during fitusiran treatment period will be reported
次要结局
- The peak thrombin generation (TG) - pre fitusiran treatment(From Month -2 up to Day 1)
- The peak TG during fitusiran treatment(From Day 1 up to Month 4)
- The antithrombin (AT) levels during pre-fitusiran treatment(From Month -2 up to Day 1)
- The AT levels during fitusiran prophylaxis(From Day 1 up to Month 4)
- Emicizumab concentrations in plasma(Up to Month 4 of fitusiran treatment)
- Number of participants with AEs from Day 1 to Month 18 of fitusiran treatment(From Day 1 up to Month 18)
- Change in participants' overall treatment satisfaction during the fitusiran treatment period assessed via the Treatment Satisfaction Questionnaire for Medication (TSQM-9) domain scores(From approximately Month -2 to Month 19 [end of study (EoS) visit])
- Participants' treatment preferences (via the Preference Questionnaire)(At Month 12)
- Change in adult participants' pain intensity during the fitusiran treatment period over time(From approximately Month - 2 to Month 19 (EoS) visit)
- Change in adolescent participants' pain intensity during the fitusiran treatment period over time(From approximately Month - 2 to Month 19 (EoS) visit)
- Change in participants' physical functioning and physical activity during the fitusiran treatment period (via the International Physical Activity Questionnaire [IPAQ]) over time(From approximately Month - 2 to Month 19 (EoS) visit)
- Change in participants' joint health (via the Hemophilia Joint Health Score [HJHS]) during the fitusiran treatment period over time(From approximately Month - 2 to Month 19 (EoS) visit)
- Annualized Bleeding Rate (ABR) while receiving fitusiran prophylaxis(From Month 4 up to Month 18 (14-month extension period))
- Emicizumab concentrations in plasma(Up to Month 4 of fitusiran treatment)
- Number of participants with AEs from Day 1 to Month 18 of fitusiran treatment(From Day 1 up to Month 18)
- Change in participants' overall treatment satisfaction during the fitusiran treatment period assessed via the Treatment Satisfaction Questionnaire for Medication (TSQM-9) domain scores(From approximately Month -2 to Month 19 [end of study (EoS) visit])
- Participants' treatment preferences (via the Preference Questionnaire)(At Month 12)
- Change in participants' physical functioning and physical activity during the fitusiran treatment period (via the International Physical Activity Questionnaire [IPAQ]) over time(From approximately Month - 2 to Month 19 (EoS) visit)
- Change in participants' joint health (via the Hemophilia Joint Health Score [HJHS]) during the fitusiran treatment period over time(From approximately Month - 2 to Month 19 (EoS) visit)
- Annualized Bleeding Rate (ABR) while receiving fitusiran prophylaxis(From Month 4 up to Month 18 (14-month extension period))
- The peak thrombin generation (TG) - pre fitusiran treatment(From Month -2 up to Day 1)
- The peak TG during fitusiran treatment(From Day 1 up to Month 4)