A Phase II Randomized, Double-Blind, Placebo Controlled Study of the Clinical Effectiveness of a Human Monoclonal Antibody Against Hepatitis C Virus E2 Glycoprotein (MBL-HCV1) in Hepatitis C Infected Patients Undergoing Liver Transplantation
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 13
- 试验地点
- 15
- 主要终点
- Proportion of Subjects With Detectable Serum HCV RNA at Day 42 Post-Transplantation
研究概览
简要总结
The purpose of this study is to determine whether a human monoclonal antibody against Hepatitis C (MBL-HCV1) is effective in preventing detectable levels of Hepatitis C virus in patients undergoing liver transplantation due to chronic HCV infection. The study will also determine if MBL-HCV1 is effective in delaying or reducing the amount of detectable HCV in patients after transplant.
详细描述
This is a Phase 2, randomized, double-blind, placebo controlled study in Hepatitis C (HCV) infected patients undergoing liver transplantation. Chronically infected patients with HCV genotype 1a scheduled to receive a liver transplant from either a deceased or living donor who satisfy all study inclusion or exclusion criteria will be approached to participate. The study will be conducted in two parts to test a human monoclonal antibody against Hepatitis C (MBL-HCV1). In Part 1, sixteen eligible patients will be randomized 1:1 to receive 50 mg/kg MBL-HCV1 or 0.9% sodium chloride placebo intravenously. Eleven doses will be given during the first 14 days post transplantation. Patients will be evaluated through day 56 for safety and clinical outcomes that include measurement of anti-HCV antibodies, anti-drug antibody and HCV viral load. On study visit day 42, a liver biopsy will be performed for evaluation of hepatitis. Physical examination, vital sign measurements, emergence of adverse events and concomitant medication usage will be assessed at scheduled visits and as needed during the 56 day study period.
The Data Safety and Monitoring Board will perform a futility analysis after the first 16 patients have been enrolled and completed study follow-up through study visit day 42 post transplant. Based on the results of the interim analysis, the dose of MBL-HCV1 for part 2 of the study will be determined. Part 2 of the study will be conducted in the same manner as Part 1.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient ≥ 18 years of age with documented chronic hepatitis C virus infection of genotype 1a undergoing liver transplantation from either a deceased donor or living donor.
- •Patient or legal guardian/health care proxy must have read, understood and provided written informed consent and HIPAA authorization after the nature of the study has been fully explained.
排除标准
- •Positive serology for Hepatitis B surface Antigen
- •Positive serology for HIV
- •Pregnancy or breastfeeding
- •Previous history of any organ transplant
- •Planned receipt of combined organ transplant (e.g. liver and kidney)
- •Receipt or planned receipt of immune globulin (IVIG) within 90 days of enrollment
- •History of extrahepatic malignancy and/or receiving chemotherapy within 90 days prior to enrollment with the exception of chemoembolization for hepatocellular carcinoma
- •Hepatocellular carcinoma with tumor burden outside of the Milan criteria
- •History of chronic renal insufficiency or creatinine > 2.5 for ≥ six months
- •Personal or family history of deep venous thrombosis or pulmonary embolism
- •Receipt of liver allograft from HCV positive donor or Hepatitis B core antibody positive donor
- •Receipt of liver allograft donated after cardiac death of donor
- •Receipt of any antiviral agents, licensed or investigational for hepatitis C virus within 90 days prior to enrollment
- •Receipt of any other investigational study product within 30 days prior to enrollment
- •Any other condition that in the opinion of the investigator would jeopardize the safety or rights of the patient participating in the study or make it unlikely that the patient could complete the study
结局指标
主要结局
Proportion of Subjects With Detectable Serum HCV RNA at Day 42 Post-Transplantation
时间窗: At Day 42 post-transplantation
Serum HCV RNA was measured by Quantitative RT-PCR
次要结局
- The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation(Through Day 56)
- Change in Serum HCV RNA Between Baseline and Day 3, 14, 28 and 42 Post-Transplantation(Baseline and Day 3, 14, 28 and 42 Post-Transplantation)
- Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR)(Through Day 56)
- Time to Onset of Recurrence of Detectable HCV RNA Post-Transplantation(Through Day 56)
- Histologic Evidence of Hepatitis by Histologic Activity Index (HAI) Score at Baseline and Day 42(Baseline Day 0 and Day 42)
- Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT)(Through Day 56)
- Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin(Through Day 56)