PROTECT - Pegylated Interferon Alfa-2b and Ribavirin After Orthotopic Liver Transplantation: Efficacy and Safety in Hepatitis C Recurrence Therapy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 125
- 主要终点
- A Sustained Virologic Response (SVR), Defined as a Plasma HCV RNA Level Below the Lower Level of Quantitation (LLQ) at 24 Weeks Post-treatment
研究概览
简要总结
This is an exploratory study and is a Phase 3, single-arm, multi-center, open-label study of pegylated interferon alfa-2b, PEG-IFN alpha-2b (PEG-Intron) and ribavirin (RBV) to determine the sustained virologic response (SVR) at 24-week follow-up to 48 week in subjects after orthotopic liver transplantation (OLT) with chronic hepatitis C (HCV) recurrence.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must confirm that all prior medication washout times have been observed.
- •Subject must be 18 - 70 years of age of either gender and of any race.
- •Subject must be transplanted for end-stage hepatitis C or fulminant hepatitis C.
- •Subject must have documented:
- •persistent HCV viremia after OLT as defined by plasma positive for HCV RNA by quantitative reverse transcription-polymerase chain reaction (RT-PCR),
- •A liver transplant performed at least 3 months prior to screening but not more than 3 years prior to screening.
- •Subject must be on stable doses of immunosuppression for at least 1 month.
- •Compensated liver disease with minimum hematologic, biochemical, and serologic criteria at the (Day 1) baseline visit.
- •Alpha-fetoprotein value (AFP) less than or equal to 250ng/mL. If AFP greater than 100 ng/mL, patient will need evidence of normal liver (magnetic resonance imaging) MRI and normal chest computerized tomography (CT) scan within the last 3 months or during the screening period.
- •For subjects with a history of diabetes or hypertension, clearance from an ophthalmologist has to be obtained prior to treatment start (Day 1/Visit 2).
- •Subjects with a history of mild depression may be considered for entry into this study.
- •Female subjects cannot be pregnant or breastfeeding and must be either postmenopausal, surgically sterile or using 2 methods of birth control.
- •Sexually active male subjects are practicing an acceptable, method of contraception.
- •Contraceptive measures will be reviewed with female subjects at each visit. Dual methods of contraception must be used for 1 month prior to the start of treatment and 6 months after treatment discontinuation.
- •Pregnancy tests obtained at Screen Visit and Day 1 Visit prior to the initiation of treatment must be negative.
排除标准
- •Pregnant women, women who plan to become pregnant, male subjects whose partner wants to become pregnant, and breastfeeding women (during study and up to 6 months after study completion).
- •Subject has used any investigational product within 30 days prior to Screening or is participating in any other clinical study.
- •Prior treatment for chronic hepatitis C post-liver transplant, including but not limited to antiviral or immunomodulatory product, any interferon product, or RBV, either as monotherapy or in combination.
- •Subjects with other organ transplants.
- •Any subject who received a positive hepatitis C core antibody (HBcAb) or HCV positive donor liver graft.
- •Retransplantation of the liver for rejection or graft failure.
- •Evidence of decompensated liver disease.
- •Known coagulopathies including hemophilia.
- •Known hemoglobinopathies.
- •Known glucose-6-phosphate dehydrogenase (G6PD) deficiency.
- •Hypersensitivity to alpha interferon and/or RBV.
- •Co-infection with hepatitis B virus (HBV) and/or human immunodeficiency virus (HIV).
- •Evidence of active or suspected malignancy or a history of malignancy within the last 5 years (with the exception of pre-transplant hepatocellular carcinoma histologically within the Milan criteria, and adequately treated basal or squamous cell carcinoma of the skin).
- •Any known pre-existing medical condition that could interfere with the subject's participation in and completion of the study.
- •Subject is or was a substance abuser. Subjects treated with buprenorphine (Subutex) who have been stable for 6 months may be included.
- •Patients weighing over 135 kg;
- •Is participating in any other clinical study(ies);
- •Is allergic to or has sensitivity to the study drug or its excipients.
研究组 & 干预措施
PEG-Intron plus Rebetol (RBV)
PEG-Intron plus RBV treatment for up to 48 weeks with 24-week follow up. SCH 54031 PEG-Intron 1.5 ug/kg SC per week plus SCH 18908 REBETOL twice daily (BID) PO with food, dosed as followed: Weeks 1 and 2, RBV Dose 400 mg (2 capsules, 1 AM and 1 PM). At the end of Weeks 2 and 4 of Treatment (tx), a complete blood count (CBC) was performed. An increase in RBV dose was permitted only if the hemoglobin was >10 g/dL. At Weeks 3 and 4, RBV dose was 800 mg (4 capsules, 2 AM and 2 PM). From Weeks 5 to 48, RBV doses could be increased based on subject body weight. For subjects weighing <65 kg, maximum dose of RBV was to be 800 mg (4 capsules, 2 AM and 2 PM), for subjects weighing 65-85 kg, max dose of RBV was 1000 mg/day (5 capsules, 2 AM and 3 PM), for subjects weighing >85 kg, max dose of RBV was 1200 mg/day, 6 capsules, 3 AM and 3 PM).
干预措施: Combination of (a) pegylated interferon alfa-2b and (b) rebetol (Drug)
结局指标
主要结局
A Sustained Virologic Response (SVR), Defined as a Plasma HCV RNA Level Below the Lower Level of Quantitation (LLQ) at 24 Weeks Post-treatment
时间窗: 24 weeks after completion of up to 48 weeks of therapy
Number of participants with SVR at 24-week follow up after treatment with PEG-Intron and Ribavirin in post-orthotopic liver transplant recipients with recurrent HCV.
次要结局
未报告次要终点