A Phase 1/2 Open-Label, Dose-Escalation, Safety, Tolerability, and Efficacy Study of SIG-001 in Adult Patients With Severe or Moderately-Severe Haemophilia A Without Inhibitors (SIG-001-121)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 6
- 主要终点
- Number of Participants With Treatment Emergent Adverse Events (TEAEs)
研究概览
简要总结
SIG-001-121 is a first-in-human (FIH), phase 1/2, multi-centre, open-label, dose escalation study to assess the safety, tolerability, and preliminary efficacy of SIG-001 in adults with severe or moderately severe haemophilia A without inhibitors. Up to three dose cohorts (3 patients each) are planned. Cohort expansions (up to 3 additional patients) may be triggered to collect additional information about safety and efficacy.
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 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Males aged 18 years or older
- •Diagnosis of Haemophilia A defined as ≤2% FVIII activity
- •Greater than 150 exposure days to treatment with FVIII products
- •Use of reliable barrier contraception if applicable
- •Normal levels of von Willebrand factor (VWF) antigen
- •Able and willing to provide informed consent
- •Willing to withdraw from FVIII prophylaxis during specified periods in the study
排除标准
- •Body mass index (BMI) ≥35
- •Current FVIII inhibitors (>0.6 Nijmegen Bethesda Units/mL) or prior Immune Tolerance Induction (ITI)
- •History of allergic reaction or anaphylaxis to recombinant FVIII products or SIG-001 components
- •Evidence of any bleeding disorder in addition to haemophilia A
- •Abnormal laboratory values as defined in the protocol
- •Active infection with Hepatitis B or Hepatitis C virus or currently managed with antiviral medications for Hepatitis B or C
- •Uncontrolled HIV infection
- •Active alcoholism or drug addiction during the 12 months before the screening visit
- •Active malignancy or history of malignancy in the 5 years prior to study entry
- •Participation in another investigational medicine or device study
- •Prior administration of a gene therapy product
- •Significant underlying disease or comorbidities that are a contraindication for general anaesthesia or laparoscopic procedure
结局指标
主要结局
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
时间窗: Baseline Up to 115 Weeks
Number of Participants with at least one TEAEs are reported. A summary of other nonserious adverse events (AEs), and all serious adverse events (SAE's), regardless of causality, is located in the Reported Adverse Events section.
Number of Participants With Serious Treatment Emergent Adverse Events (TEAEs)
时间窗: Baseline Up to 115 Weeks
Number of Participants with at least one serious TEAEs are reported. A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.
次要结局
- Change From Baseline in FVIII Activity Levels Assessed by One-stage and Chromogenic Assays(Baseline Up to 115 Weeks)
- Number of Participants With Inhibitor Titer Values Assessed by Nijmegen Bethesda Assay(Baseline Up to 115 Weeks)
- Number of Bleeding Events [Annualized Bleeding Rate (ABR)] for All Bleeds Following SIG-001 Administration(Time Frame: Pre-infusion (bleeding events in 12 months prior to sphere placement), 1 year, 2 year and 3-year post-infusion (post sphere placement) from SIG-001 administration annualized up to 115 Weeks.)
- Total Number of Replacement FVIII Therapies(Baseline Up to 115 weeks)