A Phase 1/2 Open-Label, Single Ascending Dose Trial of a Self-Complementing Optimized Adeno-associated Virus Serotype 8 Factor IX Gene Therapy (AskBio009) in Adults With Hemophilia B
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 30
- 试验地点
- 15
- 主要终点
- Number of patients experiencing treatment-related adverse events by dose group
研究概览
简要总结
The purpose of this study is to evaluate the safety of single ascending IV doses of a Factor IX (FIX) Gene Therapy in up to 16 Adults with Hemophilia B.
详细描述
Hemophilia B is a genetic X-linked bleeding disorder caused by a deficiency in blood-clotting Factor IX (FIX) activity. FIX is synthesized in the liver and circulates in the blood as a proenzyme. Current treatment for hemophilia B is based on replacement of the deficient FIX with IV injections of recombinant FIX protein prophylactically or as needed to treat bleeding episodes. This clinical program will test a gene transfer approach involving the use of a gene delivery vector carrying a FIX gene. This first-in-humans study is intended to evaluate the safety, kinetics, and if possible, the dose of AskBio009 required to achieve stable plasma FIX activity between 10% and 40% of normal activity.
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 75 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Males age 18-75 years, inclusive
- •Established hemophilia B with ≥3 hemorrhages per year requiring treatment with exogenous FIX OR use of FIX prophylaxis because of history of frequent bleeding episodes
- •Plasma FIX activity ≤2% (<1% for first cohort; then per protocol)
- •Negative for active Hepatitis C virus (HCV), defined as Hepatitis C virus antibody negative and negative (undetectable) PCR test for plasma Hepatitis C virus ribonucleic acid (RNA) OR if Hepatitis C virus antibody positive must have ≥2 consecutive negative (undetectable) PCR tests for plasma HCV RNA at least 3 months apart, and negative at screening
排除标准
- •Family history of inhibitor to FIX protein or personal laboratory evidence of having developed inhibitors to FIX protein at any time (>0.6 Bethesda Units on any single test)
- •Documented prior allergic reaction to any FIX product
- •Detectable AAV8 neutralizing antibodies
- •Markers of hepatic inflammation or overt or occult cirrhosis as evidenced by one or more of the following:
- •Platelet count <175,000/μL
- •Albumin ≤3.5 g/dL
- •Total bilirubin >1.5 x ULN and direct bilirubin ≥0.5 mg/dL
- •Alkaline phosphatase >2.0 x ULN
- •ALT or AST >2.0 x ULN (except for subjects who are HIV infected)
- •Liver biopsy in the past indicating moderate or severe fibrosis (Metavir staging of 2 or greater)
- •History of ascites, varices, variceal hemorrhage or hepatic encephalopathy
研究组 & 干预措施
AskBio009 Dose Escalation
Single Dose of a Self-Complementing Optimized Adeno-associated Virus (AAV) Serotype 8 Factor IX Gene Therapy
干预措施: AskBio009 (Biological)
结局指标
主要结局
Number of patients experiencing treatment-related adverse events by dose group
时间窗: Infusion to Week 3 and Infusion to end of study
Change from baseline in clinical laboratory evaluations
时间窗: Change from baseline at week 3 and change from baseline at the end of study
次要结局
- Detection of AskBio009 genomes in blood, saliva, urine, stool, and semen(At multiple timepoints from pre-dose through up to 1 years post-dose)
- Changes from Baseline in FIX activity levels, FIX protein levels, and Bleeding Episode Severity & Frequency(At multiple timepoints from pre-dose through up to 5 years post-dose)
- Immune Response to AskBio009(At multiple timepoints from pre-dose through up to 5 years post-dose)