A Phase 3, Single-arm, Multicenter, Multinational, Open-label, One-way Crossover Study to Investigate the Efficacy and Safety of Fitusiran Prophylaxis in Male Participants Aged ≥ 12 Years With Severe Hemophilia A or B With or Without Inhibitory Antibodies to Factor VIII or IX
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- Sanofi
- 入组人数
- 91
- 试验地点
- 85
- 主要终点
- Annualized bleeding rate (ABR) in the fitusiran primary efficacy period
研究概览
简要总结
This is a multicenter, multinational, open-label, one-way cross-over, Phase 3, single-arm study for treatment of hemophilia.
The purpose of this study is to measure the frequency of treated bleeding episodes with fitusiran in male adult and adolescent (≥12 years old) participants with hemophilia A or B, with or without inhibitory antibodies to factor VIII or IX who have switched from their prior standard of care treatment.
The total study duration will be up to approximately 50 months (200 weeks, 1 study month is equivalent to 4 weeks) and will include:
- A screening period up to approximately 60 days,
- A standard of care (SOC) period of approximately 6 study months (24 weeks),
- A fitusiran treatment period of approximately 36 study months (144 weeks),
- An antithrombin (AT) follow-up period of approximately 6 study months (24 weeks) but may be shorter or longer depending on individual participants AT recovery.
The frequency for telephone visits will be approximately every 2 weeks. For site visits the frequency will be approximately every 8 weeks during the SOC period and approximately every 4 weeks during the fitusiran treatment period. If applicable and if allowed by local regulation, home and/or remote visits may be conducted during the study
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Crossover
- 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
- •Diagnosis of severe congenital hemophilia A or B (FVIII <1% or FIX level ≤2%) as evidenced by a central laboratory measurement at screening or documented medical record evidence.
- •For participants currently not on prophylaxis (CFC or BPA on-demand): A minimum of 4 bleeding episodes requiring BPA (inhibitor participants) or CFC (non-inhibitor participants) treatment within the last 6 months prior to screening.
- •Willing and able to comply with the study requirements and to provide written informed consent and assent in the case of participants under the age of legal consent, per local and national requirements
排除标准
- •Known co-existing bleeding disorders other than congenital hemophilia A or B
- •History of arterial or venous thromboembolism, not associated with an indwelling venous access
- •History of intolerance to SC injection(s).
- •Current participation in immune tolerance induction therapy (ITI)
- •Prior gene therapy
- •Current or prior participation in a fitusiran trial
- •Current or prior participation in a gene therapy trial
- •Received an investigational drug or device within 30 days prior to the screening visit or within 5 half-lives of the investigational drug (or device) prior to the screening visit, whichever is longer
- •Presence of clinically significant liver disease AT activity <60% at Screening
- •Co-existing 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
All participants
In standard of care (SOC) period, participants will receive on-demand or prophylactic treatment with clotting factor concentrates (CFCs) or bypassing agents (BPAs) for 6 months (from Day -168 to Day -1). In fitusiran treatment period, participants will receive subcutaneous fitusiran prophylaxis once every other month (Q2M) or once monthly (QM) for 36 months (from Day 1 to Day 1009). In case of bleeding events participants will receive IV CFCs or BPAs. Participants may receive Antithrombin concentrate (ATIIIC) as rescue medicine.
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干预措施: Fitusiran (Drug)
All participants
In standard of care (SOC) period, participants will receive on-demand or prophylactic treatment with clotting factor concentrates (CFCs) or bypassing agents (BPAs) for 6 months (from Day -168 to Day -1). In fitusiran treatment period, participants will receive subcutaneous fitusiran prophylaxis once every other month (Q2M) or once monthly (QM) for 36 months (from Day 1 to Day 1009). In case of bleeding events participants will receive IV CFCs or BPAs. Participants may receive Antithrombin concentrate (ATIIIC) as rescue medicine.
.
干预措施: Clotting factor concentrates (CFC) or bypassing agents (BPA) (Drug)
All participants
In standard of care (SOC) period, participants will receive on-demand or prophylactic treatment with clotting factor concentrates (CFCs) or bypassing agents (BPAs) for 6 months (from Day -168 to Day -1). In fitusiran treatment period, participants will receive subcutaneous fitusiran prophylaxis once every other month (Q2M) or once monthly (QM) for 36 months (from Day 1 to Day 1009). In case of bleeding events participants will receive IV CFCs or BPAs. Participants may receive Antithrombin concentrate (ATIIIC) as rescue medicine.
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干预措施: Antithrombin concentrate (ATIIIC) (Drug)
结局指标
主要结局
Annualized bleeding rate (ABR) in the fitusiran primary efficacy period
时间窗: Day 169 to Day 505 (since the first dose of fitusiran)
A bleeding episode is defined as any occurrence of hemorrhage that requires administration of CFCs or BPAs, e.g., hemarthrosis, muscle, or mucosal bleeding.
次要结局
- Annualized bleeding rate (ABR) while on fitusiran prophylaxis in the fitusiran primary efficacy period and ABR while on prophylaxis standard of care (SOC) in the SOC period(Day 169 to Day 505 (primary efficacy period) and Day -168 to Day -1 (SOC period))
- Annualized spontaneous bleeding rate in the fitusiran primary efficacy period and in the SOC period(Day 169 to Day 505 (primary efficacy period) and Day -168 to Day -1 (SOC period))
- Annualized bleeding rate (ABR) while on fitusiran prophylaxis in the fitusiran primary efficacy period and ABR while on on-demand standard of care (SOC) in the SOC period(Day 169 to Day 505 (primary efficacy period) and Day -168 to Day -1 (SOC period))
- Annualized joint bleeding rate in the fitusiran primary efficacy period and in the SOC period(Day 169 to Day 505 (primary efficacy period) and Day -168 to Day -1 (SOC period))
- Change in Haem-A-QOL physical health score and total score during SOC and during fitusiran prophylaxis(Day 1 (D1) to Day 505, and from D1 to Day 1009, and during SOC from Day-168 to D-1)
- Annualized bleeding rate (ABR) in the fitusiran 18-month efficacy period(Day 1 to Day 505)
- Annualized bleeding rate (ABR) in the fitusiran 36-month treatment period(Day 1 to Day 1009)
- Number of participants with adverse events(Date of signed ICF (Day -228 to Day -169) until last visit (approximately 50 months after date of signed ICF))
- Annualized weight-adjusted consumption of CFC/BPA(Day -168 until Day 1009)