A 2-Part, Open Label Study of Telaprevir in Combination With Peginterferon Alfa-2a (Pegasys®) and Ribavirin (Copegus®) in Subjects Chronically Infected With Genotype 1 Hepatitis C Virus Following Liver Transplantation
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 61
- 试验地点
- 16
- 主要终点
- Percentage of Participants With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12)
研究概览
简要总结
To assess efficacy of telaprevir, pegylated interferon alfa-2a (Peg-IFN-alfa-2a), and ribavirin (RBV) for hepatitis C virus (HCV) in a 48-week total treatment duration regimen following liver transplantation.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female participants between the ages of 18 and 65 years
- •History of orthotopic liver transplantation less than 10 years before the Screening visit but no sooner than 6 months before Day 1
- •Taking a stable immunosuppressant regimen based on either tacrolimus or cyclosporine without substantial dose changes over the past 3 months
- •Naive to pegylated interferon/ribavirin treatment or experienced with pegylated interferon/ribavirin prior to transplantation with relapse, partial, or null response
排除标准
- •Documented cirrhosis after liver transplantation
- •Ascites or hepatic encephalopathy within 6 months before Screening
- •Retransplantation for recurrent hepatitis C
- •Treatment for hepatitis C post liver transplantation
- •History within the past 3 months of: rejection within 3 months or greater than (>) 1 rejection within 12 months
- •Current treatment with sirolimus or methylprednisolone. Low dose prednisone use (<5 milligram per day) is permitted
- •History within 3 months of any bacterial infection requiring >1 week of intravenous antibiotics, cytomegalovirus viremia or cytomegalovirus infection with end-organ involvement, fungal disease (except cutaneous and mild oral thrush)
- •History of post transplant lymphoproliferative disease
- •Acceptable laboratory values at Screening as specified in the protocol
- •Positive for human immunodeficiency virus 1/2 (HIV1/2) enzyme immunoassay (EIA) antibody screen or Hepatitis B deoxyribonucleic acid (DNA) or Hepatitis B surface antigen
- •History of hepatocellular carcinoma with high risk of recurrence
- •Any other cause of liver disease deemed clinically significant by the investigator in addition to hepatitis C
- •Autoimmune-mediated disease
- •History of acute pancreatitis within 5 years before the Screening visit
- •Prior treatment with an hepatitis C virus (HCV) protease inhibitor
研究组 & 干预措施
T/PR + Immunosuppressant Regimen (Tacrolimus)
Participants who were receiving tacrolimus (TAC) based immunosuppressant regimen at baseline, received telaprevir (T) 1125 milligram (mg) tablet twice daily for 12 weeks in combination with pegylated interferon alfa 2a (P) (Peg-IFN-alfa-2a) 180 microgram per week (mcg/week) subcutaneous injection and ribavirin (R) (RBV) tablet orally twice daily at a dose of 1000 milligram per day (mg/day) for subjects weighing less than (<) 75 kilogram (kg) and 1200 mg/day for subjects weighing greater than or equal to (>=) 75 kg, for 48 weeks. Participants continued their immunosuppressant regimen, as per standard practice and investigator discretion.
干预措施: Telaprevir (Drug)
T/PR + Immunosuppressant Regimen (Tacrolimus)
Participants who were receiving tacrolimus (TAC) based immunosuppressant regimen at baseline, received telaprevir (T) 1125 milligram (mg) tablet twice daily for 12 weeks in combination with pegylated interferon alfa 2a (P) (Peg-IFN-alfa-2a) 180 microgram per week (mcg/week) subcutaneous injection and ribavirin (R) (RBV) tablet orally twice daily at a dose of 1000 milligram per day (mg/day) for subjects weighing less than (<) 75 kilogram (kg) and 1200 mg/day for subjects weighing greater than or equal to (>=) 75 kg, for 48 weeks. Participants continued their immunosuppressant regimen, as per standard practice and investigator discretion.
干预措施: Ribavirin (Drug)
T/PR + Immunosuppressant Regimen (Tacrolimus)
Participants who were receiving tacrolimus (TAC) based immunosuppressant regimen at baseline, received telaprevir (T) 1125 milligram (mg) tablet twice daily for 12 weeks in combination with pegylated interferon alfa 2a (P) (Peg-IFN-alfa-2a) 180 microgram per week (mcg/week) subcutaneous injection and ribavirin (R) (RBV) tablet orally twice daily at a dose of 1000 milligram per day (mg/day) for subjects weighing less than (<) 75 kilogram (kg) and 1200 mg/day for subjects weighing greater than or equal to (>=) 75 kg, for 48 weeks. Participants continued their immunosuppressant regimen, as per standard practice and investigator discretion.
干预措施: Pegylated Interferon Alfa-2a (Drug)
T/PR + Immunosuppressant Regimen (Tacrolimus)
Participants who were receiving tacrolimus (TAC) based immunosuppressant regimen at baseline, received telaprevir (T) 1125 milligram (mg) tablet twice daily for 12 weeks in combination with pegylated interferon alfa 2a (P) (Peg-IFN-alfa-2a) 180 microgram per week (mcg/week) subcutaneous injection and ribavirin (R) (RBV) tablet orally twice daily at a dose of 1000 milligram per day (mg/day) for subjects weighing less than (<) 75 kilogram (kg) and 1200 mg/day for subjects weighing greater than or equal to (>=) 75 kg, for 48 weeks. Participants continued their immunosuppressant regimen, as per standard practice and investigator discretion.
干预措施: Immunosuppressant Regimen (Drug)
T/PR + Immunosuppressant Regimen (Cyclosporine)
Participants who were receiving cyclosporine (CsA) based immunosuppressant regimen at baseline, received telaprevir 1125 mg tablet twice daily for 12 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing <75 kg and 1200 mg/day for subjects weighing >=75 kg, for 48 weeks. Participants continued their immunosuppressant regimen, as per standard practice and investigator discretion.
干预措施: Telaprevir (Drug)
T/PR + Immunosuppressant Regimen (Cyclosporine)
Participants who were receiving cyclosporine (CsA) based immunosuppressant regimen at baseline, received telaprevir 1125 mg tablet twice daily for 12 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing <75 kg and 1200 mg/day for subjects weighing >=75 kg, for 48 weeks. Participants continued their immunosuppressant regimen, as per standard practice and investigator discretion.
干预措施: Ribavirin (Drug)
T/PR + Immunosuppressant Regimen (Cyclosporine)
Participants who were receiving cyclosporine (CsA) based immunosuppressant regimen at baseline, received telaprevir 1125 mg tablet twice daily for 12 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing <75 kg and 1200 mg/day for subjects weighing >=75 kg, for 48 weeks. Participants continued their immunosuppressant regimen, as per standard practice and investigator discretion.
干预措施: Pegylated Interferon Alfa-2a (Drug)
T/PR + Immunosuppressant Regimen (Cyclosporine)
Participants who were receiving cyclosporine (CsA) based immunosuppressant regimen at baseline, received telaprevir 1125 mg tablet twice daily for 12 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing <75 kg and 1200 mg/day for subjects weighing >=75 kg, for 48 weeks. Participants continued their immunosuppressant regimen, as per standard practice and investigator discretion.
干预措施: Immunosuppressant Regimen (Drug)
结局指标
主要结局
Percentage of Participants With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12)
时间窗: 12 weeks after last planned dose of study drug (up to Week 60)
SVR12 was defined as an undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (\<lower limit of quantification) at 12 weeks after last planned dose of study treatment. The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 international units per milliliter (IU/mL).
次要结局
- Percentage of Participants With Sustained Viral Response 24 Weeks After Last Planned Dose of Study Drug (SVR24)(24 weeks after last planned dose of study drug (up to Week 72))
- Number of Participants With Telaprevir Resistant HCV Variant at Non-Structural Viral Protein 3-4A (NS3-4A) Region(48 weeks)
- Percentage of Participants With Rapid Viral Response (RVR)(Week 4)
- Percentage of Participants With Viral Relapse(48 weeks)
- Percentage of Participants With Extended Rapid Viral Response (eRVR)(Week 4 and Week 12)
- Percentage of Participants With On-Treatment Virologic Failure(Baseline up to Week 48)
- Percentage of Participants With Histological Evidence of Stabilization or Improvement in Inflammation Grade or Fibrosis Stage(48 weeks)
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(Baseline up to Week 52)
- Pharmacokinetics of Telaprevir, Peg-IFN, RBV , and Selected Immunosuppressant Medications (Tacrolimus and Cyclosporine)(48 weeks)
- Percentage of Participants With Biopsy Confirmed and Treated Rejection(48 weeks)
- Percentage of Participants Requiring Dose Titration of Immunosuppressant Medications(48 weeks)