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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Liver Cirrhosis; HIV Infections; Hepatitis C
• Intervention / Treatment: Drug: Peg interferon alpha-2b

• Study Type: Interventional
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 69 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Collaborators: Integrated Therapeutics Group

Study record dates

Study Major Dates

• Study Start: September 1, 2006

Study Registration Dates

• First Submitted: September 26, 2006
• First Submitted That Met QC Criteria: September 26, 2006
• First Posted (Estimate): September 27, 2006

Study Record Updates

• Last Update Posted (Estimate): August 13, 2014
• Last Update Submitted That Met QC Criteria: August 11, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Fibrosis; Hepatitis; Hepatitis A; Hepatitis C; Liver Cirrhosis; Physiological Effects of Drugs; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Immunologic Factors; Interferons; Interferon-alpha; Interferon alpha-2; Peginterferon alfa-2b
• Other Study ID Numbers: P04371; EUDRACT NUMBER:2005-003876-39