A Phase I, Open-Label, Ascending Dose Study to Assess the Safety and Tolerability of AAV2/6 Factor IX Gene Therapy Via Zinc Finger Nuclease (ZFN) Mediated Targeted Integration of SB-FIX in Adult Subjects With Severe Hemophilia B
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 2
- 主要终点
- Number of Participants With Treatment Related Adverse Events in Subjects Who Received SB-FIX as Assessed by Common Terminology Criteria for Adverse Events (CTCAE)
研究概览
简要总结
The purpose of the study is to evaluate the safety, tolerability and effect on FIX antigen and activity levels of ascending doses of SB-FIX. SB-FIX is an intravenously delivered Zinc Finger Nuclease (ZFN) Therapeutic for genome editing. It inserts a correct copy of the Factor 9 gene into the albumin locus in hepatocytes with the goal of lifelong therapeutic production of the Factor IX clotting factor.
详细描述
The objective of the study is to provide long term expression of Factor IX in subjects with severe hemophilia B. SB-FIX is a therapeutic for ZFN-mediated genome editing which will be delivered by adeno-associated virus (AAV)-derived vectors. SB-FIX is intended to function by placement of a corrective copy of the Factor IX transgene into the genome of the subject's own hepatocytes, under the control of the highly expressed endogenous albumin locus, and is expected to provide permanent, liver-specific expression of Factor IX for the lifetime of a hemophilia B subject.
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 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Male >18 years of age
- •Severe hemophilia B (native circulating FIX activity <1%, with or without cross reactive material)
排除标准
- •Presence of neutralizing antibodies
- •History of hypersensitivity response or an allergic reaction to FIX or FIX products
- •Currently receiving long acting FIX replacement therapy
- •FIX mutations known to be associated with FIX inhibitors
- •Polymorphisms in the ZFN target region
- •Presence of any liver mass on MRI, or elevated alpha-fetoprotein (AFP)
- •Any contraindication to the use of corticosteroids for immunosuppression
- •Currently receiving antiviral therapy for hepatitis B or C or with history or active hepatitis B or hepatitis C or HIV-1 or HIV1/2 antibody positive.
- •Chronic anemia, leukopenia, or thrombocytopenia
- •Past medical history of active tuberculosis or significant fungal disease
- •Symptomatic cardiovascular disease as a co-morbid condition
- •Markers of hepatic inflammation or overt or occult cirrhosis
- •History of chronic renal disease or creatinine ≥ 1.5 mg/dL
- •Systemic (iv or oral) immunomodulatory agent or steroid use (topical treatment is allowed)
- •History of chronic infection or other chronic disorder considered an unacceptable risk
- •History of malignancy except for treated basal cell or squamous cell carcinoma
- •History of alcohol or substance abuse
- •Previously received gene therapy product
- •Participation in prior investigational drug or medical device study within the previous 3 months
- •History of therapeutic non-adherence
- •Any other reason that, in the opinion of the Investigator or Medical Monitor, would render the subject unsuitable for participation in the study
结局指标
主要结局
Number of Participants With Treatment Related Adverse Events in Subjects Who Received SB-FIX as Assessed by Common Terminology Criteria for Adverse Events (CTCAE)
时间窗: Up to 36 months after the SB-FIX infusion
Number of Participants with Treatment Related Adverse Events in Subjects Who Received SB-FIX as Assessed by Common Terminology Criteria for Adverse Events (CTCAE).
次要结局
- Presence and Shedding of AAV2/6 Vector DNA (in Copies/100ng) by PCR in Saliva, Stool and Semen(From baseline through week 20 after SB-FIX infusion)
- Change From Baseline in Factor 9 Antigen Levels Measured in IU/mL and Factor 9 Activity Levels Measured in IU/mL at Week 28 After SB-FIX Infusion(From screening through to week 28 after SB-FIX infusion)
- Frequency and Severity of Bleeding Episodes(From baseline through 36 months after the SB-FIX infusion)
- Presence of Shedding of AAV2/6 Vector DNA (in Copies/10 µL) by PCR in Plasma(From baseline through week 20 after SB-FIX infusion)
- Use of Factor IX Replacement Therapy(From baseline through 36 months after the SB-FIX infusion)
- Immune Response to FIX(Change from baseline through 28 weeks after the SB-FIX infusion)
- Presence and Shedding of AAV2/6 Vector DNA (in Copies/250 µL) by PCR in Urine(From baseline through week 12 after SB-FIX infusion)