NCT04370054进行中（未招募）3 期
Phase 3, Open-Label, Single-Arm Study to Evaluate the Efficacy and Safety of PF-07055480 (Recombinant AAV2/6 Human Factor VIII Gene Therapy) in Adult Male Participants With Moderately Severe to Severe Hemophilia A(FVIII:C≤1%)
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- Pfizer
- 入组人数
- 77
- 试验地点
- 80
- 主要终点
- Total Annualized Bleeding Rate (ABR)
研究概览
简要总结
C3731003 is a pivotal Phase 3 study to evaluate the clinical efficacy and safety of a single IV infusion of PF-07055480 / giroctocogene fitelparvovec (Recombinant AAV2/6 Human Factor VIII Gene Therapy) in adult male participants with moderately severe or severe hemophilia A (FVIII:C≤1%) for the study duration of 5 years. The study will enroll eligible participants who have been followed on routine prophylaxis with FVIII products in the Lead-In study C0371004.
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
- 18 Years 至 64 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Main inclusion Criteria
- •Males who have been followed on routine Factor VIII prophylaxis therapy during the lead-in study (C0371004) and have > = 150 documented exposure days to a Factor VIII protein product
- •Moderately severe to severe hemophilia A (Factor VIII activity < =1%)
- •Suspension of FVIII prophylaxis therapy post study drug infusion
排除标准
- •Anti-AAV6 neutralizing antibodies
- •History of inhibitor to Factor VIII
- •Laboratory values at screening visit that are abnormal or outside acceptable study limits
- •Significant and/or unstable liver disease, biliary disease, significant liver fibrosis
- •Conditions associated with increased thromboembolic risk such as inherited or acquired thrombophilia, or a history of thrombotic events
- •Planned surgical procedure requiring Factor VIII surgical prophylactic factor treatment 12 months from screening visit
- •Active hepatitis B or C
- •Serological evidence of human immunodeficiency virus HIV-1 or HIV-2 with Cluster of Differentiation 4 positive (CD4+) cell count ≤200 mm3 and/or viral load >20 copies/mL
研究组 & 干预措施
PF-07055480 (giroctocogene fitelparvovec)
Experimental
Single administration of PF-07055480
干预措施: PF-07055480 (giroctocogene fitelparovec): Recombinant AAV2/6 Human Factor VIII Gene Therapy (Biological)
结局指标
主要结局
Total Annualized Bleeding Rate (ABR)
时间窗: FVIII Prophylaxis arm: a minimum of 7.4 months, up to maximum of 32.3 months (Pre-infusion period); PF-07055480 arm: Week 12 through at least 15 months of follow-up, maximum follow up was of 44.4 months (Post-infusion period)
Bleeds for evaluation included both treated and untreated bleeds. Treated bleed: bleeding event necessitated administration of coagulation factor within 72 hours of signs or symptoms of bleeding. Untreated bleed: bleeding event did not necessitate administration of coagulation factor within 72 hours of signs and symptoms of bleeding. In this outcome measure total ABR following infusion of PF-07055480 in current study (post-infusion) and on prior FVIII prophylaxis regimen prior to infusion of PF-07055480 (pre-infusion, data collected from lead-in study C0371004) were reported. Total ABR for FVIII prophylaxis= \[(Number of total bleeding episodes during pre-infusion period)\*365.25\]/ \[(Number of days of follow-up in pre-infusion period)\]. Total ABR for PF-07055480: \[(Number of total bleeding episodes during post-infusion period)\*365.25\] / \[(last date of post-infusion period - date of PF-07055480 infusion) - 77 days + 1\].
次要结局
- Percentage of Participants With Coagulation FVIII Activity Levels Greater Than (>)5 Percent (%) at 15 Months(At 15 months following infusion of PF-07055480)
- Annualized Infusion Rate (AIR) of Exogenous FVIII Activity(FVIII Prophylaxis arm: a minimum of 7.4 months, up to maximum of 32.3 months (Pre-infusion period); PF-07055480 arm: Week 12 through at least 15 months of follow-up, maximum follow up was of 44.4 months (Post-infusion period))
- Treated ABR Based on Location(FVIII Prophylaxis arm: a minimum of 7.4 months, up to maximum of 32.3 months (Pre-infusion period); PF-07055480 arm: Week 12 through at least 15 months of follow-up, maximum follow up was of 44.4 months (Post-infusion period))
- Change From Baseline in Joint Health as Measured by Hemophilia Joint Health Score (HJHS) Instrument at Weeks 24 and 52(Baseline (before infusion on Day 1); Weeks 24 and 52)
- Percentage of Participants Without Bleeds Yearly(Maximum up to 5 years post PF-07055480 infusion)
- Change From Baseline in Joint HJHS Instrument Yearly(Baseline (before infusion on Day 1); maximum up to 5 years post PF-07055480 infusion)
- Change From Baseline in Haem-A-QoL for Adults Physical Health Domain Score Yearly(Baseline (before infusion on Day 1); maximum up to 5 years post PF-07055480 infusion)
- Treated ABR(FVIII Prophylaxis arm: a minimum of 7.4 months, up to maximum of 32.3 months (Pre-infusion period); PF-07055480 arm: Week 12 through at least 15 months of follow-up, maximum follow up was of 44.4 months (Post-infusion period))
- Annualized FVIII Consumption(FVIII Prophylaxis arm: a minimum of 7.4 months, up to maximum of 32.3 months (Pre-infusion period); PF-07055480 arm: Week 12 through at least 15 months of follow-up, maximum follow up was of 44.4 months (Post-infusion period))
- FVIII Activity Levels From Week 12 Through 15 Months Following PF-07055480 Infusion(Week 12 through Month 15 following PF-07055480 Infusion)
- Total (Treated and Untreated) ABR Based on Cause(FVIII Prophylaxis arm: a minimum of 7.4 months, up to maximum of 32.3 months (Pre-infusion period); PF-07055480 arm: Week 12 through at least 15 months of follow-up, maximum follow up was of 44.4 months (Post-infusion period))
- Treated ABR Based on Cause(FVIII Prophylaxis arm: a minimum of 7.4 months, up to maximum of 32.3 months (Pre-infusion period); PF-07055480 arm: Week 12 through at least 15 months of follow-up, maximum follow up was of 44.4 months (Post-infusion period))
- Total (Treated and Untreated) ABR Based on Location(FVIII Prophylaxis arm: a minimum of 7.4 months, up to maximum of 32.3 months (Pre-infusion period); PF-07055480 arm: Week 12 through at least 15 months of follow-up, maximum follow up was of 44.4 months (Post-infusion period))
- Percentage of Participants Without Bleeds(FVIII Prophylaxis arm: a minimum of 7.4 months, up to maximum of 32.3 months (Pre-infusion period); PF-07055480 arm: Week 12 through at least 15 months of follow-up, maximum follow up was of 44.4 months (Post-infusion period))
- FVIII Activity Level at Weeks 24, 52, 65, and 104(At Weeks 24, 52, 65 and 104)
- Change From Baseline in Haemophilia Quality of Life Questionnaire (Haem-A-QoL) for Adults Physical Health Domain Score at Weeks 12, 24 and 52(Baseline (before infusion on Day 1); Weeks 12, 24 and 52)
- Change From Baseline in Hemophilia Activities List (HAL) Complex Lower Extremity Activities Component Score at Weeks 12, 24 and 52(Baseline (before infusion on Day 1); Weeks 12, 24 and 52)
- ABR for Total Bleeds (Treated and Untreated) Yearly(Maximum up to 5 years post PF-07055480 infusion)
- FVIII Activity Levels Yearly(Maximum up to 5 years post PF-07055480 infusion)
- AIR of Exogenous FVIII Yearly(Maximum up to 5 years post PF-07055480 infusion)
- Annualized FVIII Consumption Yearly(Maximum up to 5 years post PF-07055480 infusion)
- Total (Treated and Untreated) ABR Based on Cause Yearly(Maximum up to 5 years post PF-07055480 infusion)
- Treated ABR Based on Cause Yearly(Maximum up to 5 years post PF-07055480 infusion)
- Total (Treated and Untreated) ABR Based on Location Yearly(Maximum up to 5 years post PF-07055480 infusion)
- Treated ABR Based on Location Yearly(Maximum up to 5 years post PF-07055480 infusion)
- Total (Treated and Untreated) ABR Yearly(Maximum up to 5 years post PF-07055480 infusion)
- Treated ABR by Yearly(Maximum up to 5 years post PF-07055480 infusion)
- Change From Baseline in HAL Complex Lower Extremity Activities Component Score Yearly(Baseline (before infusion on Day 1); maximum up to 5 years post PF-07055480 infusion)
- Treated ABR by Cumulative Follow-up Interval(Maximum up to 5 years post PF-07055480 infusion)
- Treated ABR Based on Cause by Cumulative Follow-up Interval(Maximum up to 5 years post PF-07055480 infusion)
- Treated ABR Based on Location by Cumulative Follow-up Interval(Maximum up to 5 years post PF-07055480 infusion)
- AIR of Exogenous FVIII by Cumulative Follow-up Interval(Maximum up to 5 years post PF-07055480 infusion)
- Annualized FVIII Consumption by Cumulative Follow-up Interval(Maximum up to 5 years post PF-07055480 infusion)
- Total (Treated and Untreated) ABR Based on Cause by Cumulative Follow-up Interval(Maximum up to 5 years post PF-07055480 infusion)
- Total (Treated and Untreated) ABR Based on Location by Cumulative Follow-up Interval(Maximum up to 5 years post PF-07055480 infusion)
- Percentage of Participants Without Bleeds by Cumulative Follow-up Interval(Maximum up to 5 years post PF-07055480 infusion)
- Total ABR (Treated and Untreated) by Cumulative Follow-up Interval(Maximum up to 5 years post PF-07055480 infusion)
- Number of Participants With Adverse Events (AEs) and Severe AEs(From Day 1 up to 104 weeks after last dose of PF-07055480 (maximum for 44.4 months))
- Number of Participants With AEs of Special Interest(From Day 1 up to 104 weeks after last dose of PF-07055480 (maximum for 44.4 months))
- Number of Participants With Positive Antibodies Against Adeno-Associated Virus Vector 6 (AAV6) Capsid Protein(Maximum up to 5 years post PF-07055480 infusion)
- Number of Participants With T-cell Responses Against AAV6 Capsid and FVIII by Elispot Assay(Maximum up to 5 years post PF-07055480 infusion)
- Number of Participants With FVIII Inhibitors Status by Bethesda Assessment(Maximum up to 5 years post PF-07055480 infusion)
研究者
研究点 (80)
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相关资讯
Giroctocogene Fitelparvovec Gene Therapy Shows Sustained Bleed Control in Hemophilia A- Phase 3 AFFINE trial data reveals giroctocogene fitelparvovec significantly reduces bleeding events in hemophilia A patients compared to standard prophylaxis.
- 64% of patients experienced no bleeding episodes for nearly three years post-infusion, demonstrating long-term efficacy of the gene therapy.
- The annualized infusion rate of FVIII replacement products significantly decreased after gene therapy, showcasing reduced treatment burden.
- Giroctocogene fitelparvovec was generally well-tolerated, with manageable side effects, offering a promising alternative for hemophilia A management.last yearPfizer's Giroctocogene Fitelparvovec Shows Positive Phase 3 Results in Hemophilia A Gene Therapy- Pfizer's giroctocogene fitelparvovec gene therapy significantly reduced annualized bleeding rate (ABR) in adults with moderately severe to severe hemophilia A.
- The AFFINE study met its primary endpoint, demonstrating superiority in total ABR compared to routine Factor VIII replacement prophylaxis.
- A significant 84% of participants maintained Factor VIII activity above 5% at 15 months post-infusion, with most achieving levels ≥15%.
- The gene therapy was generally well-tolerated, offering a potential one-time treatment to reduce the burden of frequent IV infusions.2 years ago