A FACTOR IX (FIX) GENE TRANSFER, MULTI CENTER EVALUATION OF THE LONG TERM SAFETY AND EFFICACY STUDY OF PF 06838435 AND A DOSE ESCALATION SUBSTUDY IN INDIVIDUALS WITH HEMOPHILIA B
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 21
- 试验地点
- 44
- 主要终点
- Incidence of PF-06838435 related adverse events
研究概览
简要总结
Long-term safety and efficacy follow-up for participants with Hemophilia B who were previously treated in the C0371005 (formerly SPK-9001-101) study, and a dose-escalation sub-study evaluating safety, tolerability, and kinetics of a higher dose with long-term safety and efficacy follow-up. Participants in the substudy do not need to have participated in C0371005.
详细描述
Evaluation of the long-term level of persistence and potential late or delayed adverse events associated with PF-06838435 (formerly SPK-9001), assessment of the durability of the transgene expression, and determination of the effects of PF-06838435 on clinical outcomes in individuals who have previously received a single administration of PF-06838435 in the C0371005 study. Amendment 2 of this study incorporates a dose-escalation substudy to evaluate the safety, tolerability, and kinetics of a single IV infusion of PF-06838435 at a higher dose than that used in the C0371005 study. The dose-escalation participants will also be followed for long-term safety and efficacy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 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
- •This study is currently only enrolling into the dose-escalation substudy with subsequent long-term follow-up. The Eligibility Criteria for entry into the dose-escalation substudy is presented below:
- •Inclusion Criteria:
- •Able to provide informed consent and comply with requirements of the study
- •Males age 18 to 65 years with confirmed diagnosis of hemophilia B (≤2 IU/dL or ≤2% endogenous factor IX)
- •Received ≥50 exposure days to factor IX products
- •No measurable factor IX inhibitor as assessed by the central laboratory and have no prior history of inhibitors to factor IX protein
- •Agree to refrain from donating sperm and either abstain from intercourse or use reliable barrier contraception until 3 consecutive semen samples are negative for vector sequences
排除标准
- •Evidence of active hepatitis B or C
- •Currently on antiviral therapy for hepatitis B or C
- •Have significant underlying liver disease
- •Serological evidence* of HIV-1 or HIV-2 with CD4 counts ≤200/mm3 (* participants who are HIV+ and stable with CD4 count >200/mm3 and undetectable viral load are eligible to enroll)
- •Neutralizing antibody titers to the capsid portion of PF-06838435 above the established threshold
- •Sensitivity to heparin or heparin induced thrombocytopenia; sensitivity to any of the study interventions, or components thereof, or drug or other allergy
- •Previously dosed in a gene therapy research trial at any time or in an interventional clinical study within 3 months of screening visit
- •Any concurrent clinically significant major disease or condition
- •Unable or unwilling to comply with the study procedures
研究组 & 干预措施
PF-06838435 Dose-Escalation
Single intravaneous infusion of PF-06838435. After 2 participants receive initial dose, data will be evaluated and a decision will be made to escalate or reduce the dose being evaluated, increase the number of participants receiving the dose, or stop dosing. Multiple iterations may be undertaken.
干预措施: PF-06838435 (formerly SPK-9001) (Biological)
结局指标
主要结局
Incidence of PF-06838435 related adverse events
时间窗: Baseline up to Year 6
次要结局
- Incidence of clinically significant changes from baseline(Baseline up to 52 weeks)
- Coagulation Clotting Assay for FIX activity levels(Baseline up to Year 6)
- Total number of bleeding events(Baseline up to Year 6)
- Immune response against AAV capsid protein and hFIX transgene(Baseline up to 52 weeks)
- Mean and standard deviation of FIX Antigen levels(Baseline up to 52 weeks)
- Annualized (factor FIX) infusion rate(Baseline up to Year 6)
- Brief Pain Inventory(Year 2 up to Year 6)
- Incidence of protocol-defined medically important events(Baseline up to 52 weeks)
- Annualized bleeding rate (ABR)(Baseline up to Year 6)
- Total factor consumption (IU)(Baseline up to Year 6)
- Mean and standard deviation of vector-derived FIX Activity levels(Baseline up to 52 weeks)
- Haem-A-QoL(Baseline up to Year 6)
- EQ-5D-5L(Baseline up to Year 6)
- McGill Pain Questionnaire(Baseline up to 52 weeks)