Phase 3, Open-label, Single-arm Study to Evaluate Efficacy and Safety of FIX Gene Transfer With PF-06838435 (rAAV-Spark100-hFIX-R338L) in Adult Male Participants With Moderately Severe to Severe Hemophilia B (FIX:C ≤2%) (BeneGene-2)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- Pfizer
- 入组人数
- 51
- 试验地点
- 108
- 主要终点
- Annualized Bleeding Rate (ABR) for Total Bleeds (Treated and Untreated) From Week 12 to Month 15
研究概览
简要总结
This study will evaluate the efficacy and safety of PF-06838435 (a gene therapy drug) in adult male participants with moderately severe to severe hemophilia B (participants that have a Factor IX circulating activity of 2% or less). The gene therapy is designed to introduce genetic material into cells to compensate for missing or non-functioning Factor IX. Eligible study participants will have completed a minimum 6 months of routine Factor IX prophylaxis therapy during the lead in study (C0371004). Participants will be dosed once (intravenously) and will be evaluated over the course of 6 years. The main objective of the study will evaluate the annualized bleeding rate [ABR] for participants treated with gene therapy versus standard of care (SOC) therapy (FIX prophylaxis replacement regimen).
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
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Males who completed 6 months of Factor IX prophylaxis therapy during the lead-in study (C0371004) prior to providing consent at the screening visit for this study.
- •Documented moderately severe to severe hemophilia B (Factor IX activity < =2%)
- •Previous experience with FIX therapy (=>50 documented exposure days to a FIX protein product)
- •Suspension of prophylaxis therapy for hemophilia B after administration of the study drug
- •Laboratory values (hemoglobin, platelets and creatinine) within study specified limits
- •Agree to contraception until components of the drug are eliminated from their body
- •Capable of giving signed informed consent
排除标准
- •Anti-AAVRh74var neutralizing antibodies (nAb) titer above the established threshold (ie, positive for nAb).
- •History of inhibitor to Factor IX or inhibitor detected during screening. Clinical signs or symptoms of decreased response to Factor IX
- •Hypersensitivity to Factor IX replacement product or IV immunoglobulin administration
- •History of chronic infection or other chronic disease
- •Any conditions associated with increased thromboembolic risk
- •Concurrent clinically significant major disease or condition unsuitable for participation and/or may interfere with the interpretation of study results
- •Laboratory values at screening visit that are abnormal or outside acceptable study limits
- •Current unstable liver or biliary disease
- •Currently on antiviral therapy for hepatitis B or C
- •Planned surgical procedure requiring Factor IX surgical prophylactic factor treatment 15 months from screening visit
- •Use of restricted therapies (e.g., blood products, acetylsalicylic acid [aspirin] or ibuprofen, other investigational therapy, and by-passing agents)
- •Previously dosed in a gene therapy research trial at any time or in an interventional clinical study within 12 weeks of screening visit
- •Active hepatitis B or C; hepatitis B surface antigen, hepatitis B virus deoxyribonucleic acid positivity, or hepatitis C virus ribonucleic acid positivity
- •Significant liver disease
- •Serological evidence of HIV1 or HIV2 infection with either CD4+ cell count <=200 mm3 and/or a viral load >20 copies/mL
- •Study and sponsor staff involved in the conduct of the study and their families
- •Unable to comply with study procedures
- •Sensitivity to heparin or heparin induced thrombocytopenia
- •Sensitivity to any of the study interventions, or components thereof, or drug or other allergy
研究组 & 干预措施
PF-06838435/ fidanacogene elaparvovec
干预措施: PF-06838435/ fidanacogene elaparvovec (Biological)
结局指标
主要结局
Annualized Bleeding Rate (ABR) for Total Bleeds (Treated and Untreated) From Week 12 to Month 15
时间窗: Pre-infusion period: minimum of 6 months through first dose of current study, an average of 1.31 years (FIX Prophylaxis arm); Week 12 to Month 15 post infusion in current study (PF-06838435 arm)
ABR = number of total bleeding episodes on study during the given time period) \*365.25/ (Date of last day - date of first day +1) in that time period. Surgical procedures were excluded from summary/analyses. Treated Bleed: An event necessitating administration of coagulation factor within 72 hours of signs or symptoms of bleeding (protocol definition, unless specifically referring to untreated bleed). Untreated Bleed: A bleeding event not necessitating administration of coagulation factor within 72 hours of signs or symptoms of bleeding. This outcome measure compared data collected from lead-in study C0371004 and from current study C0371002. Pre-infusion period = at least 6 months of prospectively collected data while receiving FIX prophylaxis replacement therapy in lead-in study C0371004 up to dosing in current study C0371002.
次要结局
- Percentage of the Participants Without Bleeds From Week 12 to Month 15(Week 12 to Month 15)
- Change From Baseline in Joint Health as Measured by the Hemophilia Joint Health Score (HJHS) Instrument at Month 12(Baseline, Month 12)
- Steady State Circulating Factor IX (FIX:C) From Week 12 to Month 15(Week 12 to Month 15)
- Annualized Factor IX (FIX) Consumption From Week 12 to Month 15(Pre-infusion period: minimum of 6 months through first dose of current study, an average of 1.31 years (FIX Prophylaxis arm); Week 12 to Month 15 post infusion in current study (PF-06838435 arm))
- Annualized Infusion Rate (AIR) of Exogenous FIX From Week 12 to Month 15(Pre-infusion period: minimum of 6 months through first dose of current study, an average of 1.31 years (FIX Prophylaxis arm); Week 12 to Month 15 post infusion in current study (PF-06838435 arm))
- ABR for Traumatic Bleeds From Week 12 to Month 15(Pre-infusion period: minimum of 6 months through first dose of current study, an average of 1.31 years (FIX Prophylaxis arm); Week 12 to Month 15 post infusion in current study (PF-06838435 arm))
- Number of Participants With Positive Neutralizing Antibody (nAb) to Adeno-associated Virus Vector (AAV) and Anti-Drug Antibody (ADA)(Maximum up to 6 years (Week 312) after PF-06838435 infusion)
- ABR for Treated Bleeds Through the Study(Maximum up to 6 years (Week 312) after PF-06838435 infusion)
- Annualized Factor IX Consumption Through the Study(Maximum up to 6 years (Week 312) after PF-06838435 infusion)
- Change From Baseline in Joint Health as Measured by the HJHS Instrument Through the Study(Baseline, 6 years)
- Change From Baseline in Haem A QoL Physical Health Domain Through the Study(Baseline, Maximum up to 6 years (Week 312) after PF-06838435 infusion)
- Circulating Factor IX (FIX:C) at Week 12, Week 24, Week 65(Week 12, Week 24, Week 65)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs(Maximum up to 6 years (Week 312) after PF-06838435 infusion)
- Number of Participants With Adverse Events of Special Interest(Maximum up to 6 years (Week 312) after PF-06838435 infusion)
- ABR for Treated Bleeds From Week 12 to Month 15(Pre-infusion period: minimum of 6 months through first dose of current study, an average of 1.31 years (FIX Prophylaxis arm); Week 12 to Month 15 post infusion in current study (PF-06838435 arm))
- ABR for Spontaneous Bleeds From Week 12 to Month 15(Pre-infusion period: minimum of 6 months through first dose of current study, an average of 1.31 years (FIX Prophylaxis arm); Week 12 to Month 15 post infusion in current study (PF-06838435 arm))
- Number of Target Joint Bleeds From Week 12 to Month 15(Pre-infusion period: minimum of 6 months through first dose of current study, an average of 1.31 years (FIX Prophylaxis arm); Week 12 to Month 15 post infusion in current study (PF-06838435 arm))
- Number of Target Joint Bleeds Through the Study(Maximum up to 6 years (Week 312) after PF-06838435 infusion)
- ABR for Untreated Bleeds From Week 12 to Month 15(Pre-infusion period: minimum of 6 months through first dose of current study, an average of 1.31 years (FIX Prophylaxis arm); Week 12 to Month 15 post infusion in current study (PF-06838435 arm))
- Change From Baseline in Hemophilia Quality of Life (Haem A QoL) Physical Health Domain at Month 12(Baseline, Month 12)
- ABR for Spontaneous and Traumatic, and Untreated Bleeds Through the Study(Maximum up to 6 years (Week 312) after PF-06838435 infusion)
- Change From Baseline in HAL Complex Lower Extremity Activities Component Score Through the Study(Baseline, 6 years)
- Change From Baseline in Hemophilia Activities List (HAL) Complex Lower Extremity Activities Component Score at Month 12(Baseline, Month 12)
- ABR for Total Bleeds (Treated and Untreated) Through the Study(Maximum up to 6 years (Week 312) after PF-06838435 infusion)
- AIR of Exogenous Factor IX Through the Study(Maximum up to 6 years (Week 312) after PF-06838435 infusion)
- FIX: C Level Through the Study(Maximum up to 6 years (Week 312) after PF-06838435 infusion)