A Phase 3 Open-label, Multicenter Study of the Long-term Safety and Efficacy of Intravenous Recombinant Coagulation Factor VIII Fc-von Willebrand Factor-XTEN Fusion Protein (rFVIIIFc-VWF-XTEN; BIVV001) in Previously Treated Patients With Severe Hemophilia A
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 261
- 试验地点
- 170
- 主要终点
- Number of participants with the occurrence of inhibitor development (neutralizing antibodies detected against factor VIII [FVIII])
研究概览
简要总结
Primary Objective:
- To evaluate the long-term safety of BIVV001 in previously treated subjects with hemophilia A
Secondary Objectives:
- To evaluate the efficacy of BIVV001 as a prophylaxis treatment.
- To evaluate the efficacy of BIVV001 in the treatment of bleeding episodes.
- To evaluate BIVV001 consumption for prevention and treatment of bleeding episodes.
- To evaluate the effect of BIVV001 prophylaxis on joint health outcomes.
- To evaluate the effect of BIVV001 prophylaxis on Quality of Life (QoL) outcomes.
- To evaluate the safety and tolerability of BIVV001 treatment.
- To assess the PK of BIVV001 based on the one stage activated partial thromboplastin time (aPTT) and two-stage chromogenic FVIII activity assays (only applicable to Arm B).
- To evaluate the efficacy of BIVV001 for perioperative management
详细描述
Participants will receive BIVV001 once weekly for a total of at least 100 exposure days to BIVV001 (including exposure during a BIVV001 parent study, if applicable). Participants will have the opportunity to continue in this study for up to 4 years, unless BIVV001 is commercially available in their applicable participating country.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •For participants rolling over into Arm A
- •Participants who have completed the studies EFC16923, EFC16925, Arm B or Arm C of the current study, or any other potential BIVV001 study.
- •Male or Female
- •For participants new to BIVV001 (Arm B and C)
- •Participants who have severe hemophilia A, defined as <1 IU/dL (<1%) endogenous FVIII activity as documented either by central laboratory testing at screening or in historical medical records from a clinical laboratory demonstrating <1% FVIII coagulant activity (FVIII:C) or a documented genotype known to produce severe hemophilia A.
- •Previous treatment for hemophilia A (prophylaxis or on-demand) with any recombinant and/or plasma-derived FVIII, or cryoprecipitate for at least 150 EDs or 50 EDs for participants aged <6 years.
- •Platelet count ≥100 000 cells/μL at screening.
- •A participant known to be human immunodeficiency virus (HIV) antibody positive, either previously documented or identified from screening assessments, must have the following results prior to enrollment: CD4 lymphocyte count >200 cells/mm³ and viral load of <400 000 copies/mL
- •Only for Arm B: Chinese participants
- •Only for Arm C: planned major surgery within 6 months after Day 1.
排除标准
- •For participants rolling over into Arm A
- •Positive inhibitor result, defined as ≥0.6 Bethesda units (BU)/mL.
- •Participation in another study.
- •For participants new to BIVV001 (Arm B and Arm C)
- •Any concurrent clinically significant liver disease that, in the opinion of the Investigator, would make the participant unsuitable for enrollment. This may include, but is not limited to cirrhosis, portal hypertension, and acute hepatitis.
- •Serious active bacterial, fungal, or viral infection (other than chronic hepatitis or HIV) present within 30 days of screening.
- •Other known coagulation disorder(s) in addition to hemophilia A.
- •History of hypersensitivity or anaphylaxis associated with any FVIII product.
- •History of a positive inhibitor (to FVIII) test defined as ≥0.6 BU/mL, or any value greater than or equal to the lower sensitivity cut-off for laboratories with cut-offs for inhibitor detection between 0.7 and 1.0 BU/mL, or clinical signs or symptoms of decreased response to FVIII administrations. Family history of inhibitors will not exclude the participant.
- •Positive inhibitor test (FVIII) result, defined as ≥0.6 BU/mL at screening.
- •Treatment with acetylsalicylic acid (ASA) or antiplatelet agents that are not nonsteroidal anti-inflammatory drugs (NSAIDs) within 2 weeks prior to screening.
- •Treatment with NSAIDs greater than the maximum dose specified in the regional prescribing information within 2 weeks prior to screening.
- •Systemic treatment within 12 weeks prior to Screening with chemotherapy and/or other immunosuppressive drugs (except for the treatment of hepatitis C virus [HCV] or HIV).
- •Emicizumab use within the 20 weeks prior to screening.
- •Major surgery within 8 weeks prior to screening.
- •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
Arm C: Newly initiated in BIVV001 with planned major surgery
This arm includes participants of any age who will be newly initiated on BIVV001 prophylaxis treatment once-weekly (QW) and will undergo planned major surgery after at least 6 initial EDs with BIVV001, and within 26 weeks from Day 1. After 52 weeks of treatment in arm C, participants will be able to roll into arm A.
干预措施: efanesoctocog alfa (BIVV001) (Drug)
Arm A: Previously treated in BIVV001 study
This arm includes participants who have completed study EFC16293 or study EFC16295, participants who have completed Arm B or Arm C of this study (LTS16294) and roll over into Arm A, and participants who have completed any other potential BIVV001 study. Participants in this arm will continue receiving BIVV001 prophylaxis treatment once weekly (QW) for a total of 100 exposure days (EDs) cumulative from the parent study and this study. Participants will have the opportunity to continue in this study for up to 4 years, unless BIVV001 is commercially available in their applicable participating country.
干预措施: efanesoctocog alfa (BIVV001) (Drug)
Arm B: Newly initiated (China Only) in BIVV001
This arm includes Chinese participants of any age who will be newly initiated on BIVV001 prophylaxis treatment once-weekly (QW) for 52 weeks. After 52 weeks of treatment in this arm B, participants will be able to roll over into arm A.
干预措施: efanesoctocog alfa (BIVV001) (Drug)
结局指标
主要结局
Number of participants with the occurrence of inhibitor development (neutralizing antibodies detected against factor VIII [FVIII])
时间窗: Baseline to month 48
The number of participants with the occurrence of inhibitor development (neuatralizing antibodies detected against factor VIII \[FVIII\]) as determined via the Nijmegen modified Bethesda assay.
次要结局
- Percentage of patients who maintain factor VIII (FVIII) above prespecified activity levels(Baseline to month 48)
- Annual bleeding rate (ABR)(Baseline to month 48)
- Total annualized BIVV001 consumption(Baseline to month 48)
- Target joint resolution(Month 48)
- Physician's global assessment (PGA) of participants response to BIVV001(Baseline to month 48)
- Annualized bleeding rate (ABR) by type of bleed(Baseline to month 48)
- Annualized bleeding rate (ABR) by location(Baseline to month 48)
- Number of injections and dose of BIVV0001 to treat a bleeding episode(Month 48)
- Percentage of bleeding episode treated with a single injection of BIVV001(Month 48)
- Assessment of response to BIVV001 treatment of individual bleeding episodes(Baseline to month 48)
- PK parameter: Total clearance at steady state (CLss)(Baseline to week 26)
- PK parameter: Accumulation index (AI)(Baseline to week 26)
- PK parameter: Volume of distribution at steady state (Vss)(Baseline to week 26)
- PK parameter: Mean residence time (MRT)(Baseline to week 26)
- PK parameter: Incremental recovery (IR)(Baseline to week 52)
- PK parameter: Trough activity (Ctrough)(Baseline to week 52)
- Annualized joint bleeding rate (AJBR)(Baseline to month 48)
- Change from baseline in Hemophilia Joint Health Score (HJHS)(Baseline to month 48)
- Change from baseline in PROMIS-SF Physical Function(Baseline to month 48)
- PK parameter: Time above FVIII activity levels(Baseline to week 26)
- Investigators' or Surgeons' assessment of participant's hemostatic response to BIVV001 treatment(Baseline to month 48)
- Number of injections and dose to maintain hemostasis during perioperative period for major surgery(Baseline to month 48)
- Change from baseline in Haem-A-QoL total score and physical health score(Baseline to month 48)
- Change from baselin in Haemo-QoL total score and physical health score(Baseline to month 48)
- Number of participants with adverse events (AEs) and serious adverse events (SAEs)(Baseline to month 48)
- Number of participants with the occurrence of embolic and thrombotic events(Baseline to month 48)
- PK parameter: Maximum activity (Cmax)(Baseline to week 52)
- PK parameter: Elimination half-life (t1/2)(Baseline to week 26)
- PK parameter: Total clearance (CL)(Baseline to week 26)
- PK parameter: Area under the activity time curve (AUC)(Baseline to week 26)
- Total BIVV001 consumption during perioperative period for major surgery(Baseline to month 48)
- Number and type of blood component transfusions used during perioperative period for major surgery(Baseline to month 48)
- Estimated blood loss during perioperative period for major surgery(Baseline to month 48)