AN OPEN-LABEL EXTENSION STUDY TO EVALUATE THE LONG-TERM SAFETY, TOLERABILITY, AND EFFICACY OF MARSTACIMAB PROPHYLAXIS IN SEVERE (COAGULATION FACTOR ACTIVITY <1%) HEMOPHILIA A PARTICIPANTS WITH OR WITHOUT INHIBITORS OR MODERATELY SEVERE TO SEVERE HEMOPHILIA B PARTICIPANTS (COAGULATION FACTOR ACTIVITY ≤2%) WITH OR WITHOUT INHIBITORS
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- Pfizer
- 入组人数
- 245
- 试验地点
- 75
- 主要终点
- Number of subject reporting Adverse Events
研究概览
简要总结
Study B7841007 is an open-label extension study to assess the long-term safety, tolerability, and efficacy of prophylaxis treatment with marstacimab in participants who did not require "Early Termination" from the Phase 3 Study B7841005 and from the Phase 3 Study B7841008.
Study B7841005: approximately 145 adolescent and adult participants 12 to <75 years of age with severe hemophilia A or moderately severe to severe hemophilia B (defined as FVIII activity <1% or FIX activity ≤2%, respectively) with or without inhibitors are expected to be enrolled in Study B7841005 during which they will receive prophylaxis (defined as treatment by SC injection of marstacimab).
Study B7841008: this is an ongoing Phase 3, open-label study in pediatric participants <18 years of age with severe hemophilia A (FVIII Coagulation Factor Activity <1%) or moderately severe to severe hemophilia B (FIX Coagulation Factor Activity ≤2%). A sequential approach will be used in enrolling at least 100 pediatric participants, at least 20 of which will be aged ≥12 to <18 years and at least 80 participants will be aged ≥1 to <12 years. At the start of study B7841008, the dosing and data available in adolescent and adult participants in Study B7841005 supported the initiation of B7841008 study in participants aged ≥12 to <18 years. Subsequently, additional safety and efficacy data from adolescent participants in Study B7841005 became available for benefit/risk assessment in support of dosing participants aged ≥6 to <12 years. Based on the positive benefit/risk assessment conducted by both internal Pfizer review and eDMC review, dosing of the ≥6 to <12 years age group was initiated in June 2023 in B7841008 Study. Data from participants ≥6 years from B7841008 Study and Study B7841005 will support the dosing of participants aged ≥1 to <6 years.
All participants will be provided the prefilled pen (PFP) for administration of marstacimab in the study. Use of the prefilled syringe (PFS) will be permitted at the investigator's discretion for those participants who have difficulty with administration of the PFP. Additionally, participants will be provided the PFS for use in this study in countries where the PFS is anticipated to be the only presentation available commercially. An optional, open-label, single arm, substudy using the PFP was completed in the first 23 participants rolled over from Study B7841005 who agreed to participate in the substudy.
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
- 1 Year 至 74 Years（Child, Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •All participants will have a minimum body weight as defined by parent studies
- •Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures.
- •Participants have successfully completed participation in parent studies, defined as did not require "Early Termination"
排除标准
- •Previous or current treatment for or history of coronary artery disease, venous or arterial thrombosis (CTCAE Grade >3), or ischemic disease (except catheter-associated thrombosis)
- •Abnormal renal function as defined by eGFR <30 mL.min/1.73 m(2)
- •Known planned surgical procedure during the planned study period
- •Unstable hepatic function as determined by the Investigator clinical assessment and review of the participant's most recent laboratory results, which would make the participant inappropriate for the study
- •For participants known to be HIV+, worsening disease status as determined by the Investigator clinical assessment and review of participant's most recent laboratory results, to include recent locally available CD4 count (if available), which would make the participant inappropriate for the study
- •Regular, concomitant therapy with immunomodulatory drugs (eg, IVIG, and routine systemic corticosteroids, rituximab)
- •Ongoing or planned use of immune tolerance induction or prophylaxis with FVIII or FIX replacement during the study
- •Participation in other study involving investigational drug(s) or investigational vaccine(s) within 30 days or 5 half-lives prior to or during study participation, with the exception of participation in parent studies
- •Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the Investigator, and their respective family members
研究组 & 干预措施
PF-06741086
For participants aged ≥12 years 300 milligrams(mg) subcutaneous (sc) loading dose followed by 150 mg sq once weekly (qw). 300 mg sc qw is prescribed for participants who meet dose escalation criteria.
For participants aged ≥6 to <12 years is marstacimab 150 mg SC for initial loading dose followed by 75 mg SC QW. 150 mg sc qw is prescribed for participants who meet dose escalation criteria.
干预措施: PF-06741086 (Drug)
结局指标
主要结局
Number of subject reporting Adverse Events
时间窗: Baseline up to 7 years
Number of subjects reporting Serious Adverse Events
时间窗: Baseline up to 7 years
Incidence and severity of thrombotic events
时间窗: Baseline up to 7 years
Incidence and severity of thrombotic microangiopathy
时间窗: Baseline up to 7 years
Number of subjects reporting Disseminated intravascular coagulalopathy/consumption coagulopathy
时间窗: Baseline up to 7 years
Incidence of clinically significant persistent NAb against marstacimab
时间窗: Baseline up to 7 years
Incidence and severity of injection site reaction
时间窗: Baseline up to 7 years
Clinically significant changes in vital signs from baseline
时间窗: Baseline up to 7 years
Incidence of clinically significant laboratory value abnormalities
时间窗: Baseline up to 7 years
Incidence of severe hypersensitivity and anaphylactic reactions
时间窗: Baseline up to 7 years
次要结局
- Incidence of joint bleeds(Baseline up to 7 years)
- Annualized rate of bleeding episodes(Baseline up to 7 years)
- Total coagulation factor product consumption(Baseline up to 7 years)
- Incidence of spontaneous bleeds(Baseline up to 7 years)
- Incidence of target joint bleeds(Baseline up to 7 years)
- Incidence of total bleeds (treated and untreated)(Baseline up to 7 year)
- Change in joints measured by the HJHS(Baseline up to 7 years)
- Change in number of target joints per subject from baseline(Baseline up to 7 years)
- Changes in Health Utilities Measure questionnaire data(Baseline up to 7 years)
- Changes in Haem-A-QoL questionnaire data for participants ≥17 years of age(Baseline up to 7 years)
- Changes in Haemo-QoL questionnaire data(Baseline up to 7 years)
- Total bypass product consumption(Baseline up to 7 years)
- Changes in EQ-5D questionnaire data(Baseline up to 7 years)