A Phase II Open-Label Study of the Clinical Effectiveness of a Human Monoclonal Antibody Against Hepatitis C Virus E2 Glycoprotein (MBL-HCV1) Combined With Oral Direct-Acting Antivirals in Hepatitis C Infected Patients Undergoing Liver Transplantation
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 11
- 试验地点
- 5
- 主要终点
- Number of Subjects With Undetectable HCV RNA at Day 56 Post Liver Transplantation
研究概览
简要总结
The purpose of this study is to assess efficacy of a human monoclonal antibody against Hepatitis C (MBL-HCV1) combined with telaprevir [part 1: an HCV protease inhibitor] or sofosbuvir [part 2: an Hepatitis C virus NS5B polymerase inhibitor] in a 56 day treatment duration in patients undergoing liver transplantation due to chronic HCV infection. There is an option for extended study treatment through 84 days if viral load is undetectable at day 56.
详细描述
Administration of Intravenous infusions of MBL-HCV1 (50mg/kg) human monoclonal antibody during the first 14 days post-transplantation: three infusions on day 0 (1-4 hours prior to the anhepatic phase, during the anhepatic phase, and 4-12 hours post-reperfusion). Daily infusions on days 1 through 7, weekly infusions on day 14 ± 2, day 21 ± 3, and day 28 ± 3, followed by biweekly infusions on day 42 ± 3 and on day 56 ± 3 if criteria for the stopping rule are not met. For those subjects electing extended treatment, the administration of additional infusions on day 70 ± 3 and day 84 ± 3 will be performed. Subjects receive an oral direct-acting antiviral (telaprevir in Part 1 and sofosbuvir in Part 2) starting no earlier than day 3 post-transplant and no later than day 7; dosing continuing through day 56 unless criteria for the stopping rule are met. Subjects who elect to receive extended study treatment for a total of 12 weeks continue telaprevir in Part 1 or sofosbuvir in Part 2 through day 84 ± 3.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
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 1 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 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
- •Extrahepatic malignancy not currently in remission and/or receiving systemic chemotherapy and/or radiation within 90 days prior to enrollment. Exceptions include chemoembolization for hepatocellular carcinoma or cutaneous malignancies managed with local treatment
- •Hepatocellular carcinoma with tumor burden outside of the Milan criteria
- •Serum creatinine > 2.5 for > or = six months at the time of enrollment
- •Personal or family history (first degree relative) 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 30 days prior to liver transplantation, unless patient has documented detectable HCV RNA during this 30 day period
- •Previous receipt of an HCV protease inhibitor (for subjects enrolling in Part 1: telaprevir)
- •Receipt of any other investigational study product within 30 days prior to enrollment
- •Seizure disorder requiring anti-convulsant therapy
- •Pulmonary arterial hypertension requiring sildenafil or tadalafil infusion (for subjects enrolling in Part 1: telaprevir)
- •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
研究组 & 干预措施
Part 2: MBL-HCV1 and Sofosbuvir
干预措施: Sofosbuvir (Part 2) (Drug)
Part 1: MBL-HCV1 and Telaprevir
干预措施: MBL-HCV1 (Biological)
Part 1: MBL-HCV1 and Telaprevir
干预措施: Telaprevir (Part 1) (Drug)
Part 2: MBL-HCV1 and Sofosbuvir
干预措施: MBL-HCV1 (Biological)
结局指标
主要结局
Number of Subjects With Undetectable HCV RNA at Day 56 Post Liver Transplantation
时间窗: Day 56
The primary outcome was to determine if MBL-HCV1 in combination with the oral direct-acting antiviral could reduce HCV viral RNA to undetectable at day 56 post transplant and prevent the new liver from becoming productively infected. Undetectable HCV RNA was defined as the level below the lower limit of detection (LLOD) of an FDA-approved polymerase chain reaction (PCR) assay. HCV RNA was quantified by PCR (e.g., COBAS®AmpliPrep/ COBAS® TaqMan® HCV Test manufactured by Roche or equivalent) at each study site
次要结局
- Safety and Tolerability of Study Treatment by Number of Adverse Events Reported(Day 0 start of first infusion through Day 56 or six weeks after last dose of study treatment whichever is later, up to approximately 126 days)
- Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 10, 14, 28, 35, 42, 49, 70, 84 and 98 in Liver Transplant Recipients and for Those Subjects Receiving an Additional 4 Weeks of Treatment at Study Day 105, 112 and 126(Day 7, 10, 14, 28, 35, 42, 49, 70, 84, 98, 105, 112 and 126)
- Change in Viral Load Between Baseline Pre-transplant HCV RNA Levels and Study Day 7, 10, 14, 28, 35, 42, 49, 56, 70, 84 and 98 in Liver Transplant Recipients(Baseline pre-transplant and study Day 7, 10, 14, 28, 35, 42, 49, 56, 70, 84 and 98)
- Number of Participants With HCV Resistance-associated Variants to MBL-HCV1 and Oral Direct-acting Antivirals Before and After Receipt of Study Treatment(Pre-transplant, time of viral rebound (assessed from Day 7-Day 56 of treatment), end of study (up to day 126) in subjects who did not achieve a sustained virologic response (SVR))