Effects of Low-dose Maintenance Peg Interferon Alfa-2b Therapy Versus Supportive Care in Patients With Cirrhotic Hepatitis C With HIV (Study P04371)

Study Overview
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Brief Summary
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This is a Phase 3b, randomized, open-label, parallel-group, multi-center, multi-national study of low-dose maintenance Peg interferon alpha-2b (Peg-Intron®) in subjects with human immunodeficiency virus-hepatitis C virus (HIV-HCV) co-infection. The primary objective is to compare at end of study the efficacy of Peg-Intron® monotherapy (0.5 µg/kg subcutaneously once weekly for 24-36 months) versus standard supportive care, using the time to any of the following clinical events (death, decompensation, liver transplant, hepatocellular carcinoma [HCC]) as endpoints.

Official Title
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A Randomized, Open-label, Multi-center, Phase 3, 2-arm Study Evaluating the Efficacy and Safety of Peg Interferon Alfa-2b Low-dose Maintenance Monotherapy Versus Standard Supportive Care in Patients With Cirrhotic Hepatitis C Co-infected With Human Immunodeficiency Virus - The ENDURE Study

Conditions
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Hepatitis C, Liver Cirrhosis, HIV Infections

Intervention / Treatment
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* Drug: Peg interferon alpha-2b


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age at least 18 years but < 70 years, of either sex or any race. Detectable plasma hepatitis C virus (HCV) RNA (all genotypes of HCV are permitted). Cirrhosis of the liver within the last five years. Compensated liver disease (Child-Pugh <8 with hepatic encephalopathy <= 1. No evidence of hepatocellular carcinoma (HCC) and a serum alpha fetoprotein (AFP) <100 ng/mL within two months of randomization/study enrollment. Varices results via endoscopy within the last six months or at time of screening. Serologic evidence of human immunodeficiency virus-1. CD4 cell count >=100 /µL. Platelet number of at least 50000 mm**3. Neutrophil count of at least 750 mm**3. Hemoglobin of >9.0 mg%. Serum thyroid stimulating hormone levels within normal limits, regardless of treatment with L thyroxin. Hemoglobin A1c (HbA1c)<8.5%, to demonstrate controlled diabetes, if applicable. Written clearance from an ophthalmologist must be presented for subjects with a history of hypertension or diabetes prior to treatment start. Creatinine clearance >50 mL/min, as assessed by the indirect calculation method. Demonstrate stable status of HIV-1 infection. On stable antiretroviral therapy (HAART) for at least 6 weeks prior to baseline, with the expectation of their HAART regimen (drugs and dosage) remaining unaltered for the first 8 weeks of the study OR Willing to delay initiation of HAART therapy for at least 6 weeks (for subjects who have not been on HAART for at least 8 weeks prior to randomization). Structured treatment interruptions will be permitted during the study. Counseled in the appropriate use of birth control while in this study, as confirmed by the principal investigator or a sub-investigator. Free of any clinically significant disease (other than HCV and HIV) that would interfere with study evaluations. Exclusion Criteria: Female who is pregnant, intends to become pregnant during the study or within two months after study completion, or is nursing. Male subject whose partner wants to become pregnant. Using silymarin. Positive test at screening for anti-HAV IgM Ab, HBsAg, anti-HBc IgM Ab, or HBeAg. Any cause of liver disease other than chronic hepatitis C. Suspected or having hypersensitivity to interferon. History of liver decompensation status or other evidence of bleeding from esophageal varices, signs of current bleeding, significant ascites, hepatic encephalopathy, jaundice or other conditions consistent with decompensated liver disease. Present with a lesion suspicious for hepatic malignancy on the screening imaging. Any active malignant disease, suspicion, or history of malignant disease within 5 years prior to study enrollment (except for adequately treated basal cell carcinoma). Known coagulation or hemoglobin diseases. Organ transplant, except corneal or hair transplant. Any known preexisting medical condition that, in the investigator's opinion, could interfere with the subject's participation in and completion of the study, such as major depressive disorder. Active HIV-related opportunistic infection and/or malignancy requiring systemic therapy. Evidence of known severe retinopathy. Subject has not observed the designated washout periods for any of the prohibited medications. Participating in any other hepatitis C clinical study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 69 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Peg interferon alpha-2b|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |