Pegylated Alfa-2b Interferon Therapy of Patients With Hepatitis C-related Cirrhosis and High Liver Cell Proliferation (P02733/MK-4031-085)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 3

Conditions: Carcinoma, Hepatocellular

Treatments: Biological: Peginterferon alfa-2b; Other: Observation (no treatment)

Study type: Interventional

Funder types: Industry

Identifiers

NCT00759109

P02733

Details and patient eligibility

About

This study aims to compare the role of peginterferon α-2b (50 μg/week) vs. control (no treatment) in the prevention of hepatocellular carcinoma, in adult patients with cirrhosis and initial signs of portal hypertension who did not respond to previous combined therapy with interferon alfa + ribavirin or peginterferon alfa + ribavirin or to interferon alfa monotherapy and with a high proliferation rate before entering the study. The duration of treatment will be 3 years, and the follow-up period will be 2 years.

Enrollment: 150 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Cirrhotic participants, both sexes, Child Pugh A, B, HCV-RNA positive, age < 70 years

• Participants non-responders to IFN + Ribavirin or PegIFN + Ribavirin or IFN monotherapy

• Pre-therapy liver biopsy (< 36 months) with PCNA-LI > 2.0

• Fibrosis score 5-6 (Ishak)

• Initial portal hypertension, such as gastroesophageal varices or one of the following US sign:

  • Collateral circles
  • Spleen longitudinal diameter > 12 cm
  • Portal vein diameter at hilus > 12 mm
  • Portal flow > 12 cm/sec
  • Participants must have the following minimum hematologic and biochemical criteria:
  • Hemoglobin >= 11 g/dL
  • Granulocyte count > 1,000/mm^3
  • Platelets > 70,000/mm^3
  • Prothrombin activity > 50%
  • Total bilirubin <3 mg/dL
  • Albumin >= 3.5 g/dL
  • Serum creatinine within normal limits

• Uric Acid within normal limits

• Thyroid Stimulating Hormone (TSH), within normal limits

• Antinuclear antibodies (ANA) < 1:160

• Written informed consent

• Women of childbearing potential must have a negative pregnancy test

• Acceptance of patients of both sexes of proper contraceptive measures for the study period

Exclusion criteria

• Pregnant or breast-feeding women
• Co-infection with HIV and/or HBV
• Autoimmune hepatitis or history of autoimmune disease
• Alcoholic liver disease
• Metabolic disease
• HCC
• Participants with liver and kidney transplants
• Evidence of decompensated liver disease such as history or presence of ascites, bleeding varices, spontaneous encephalopathy
• Chronic renal failure or creatinine clearance < 50 mL/min
• Pre-existing thyroid disease unless it can be controlled with conventional treatment
• History or presence of psychiatric condition, especially depression, or a history of severe psychiatric disorder, such as major psychoses, suicidal ideation and/or suicidal attempt
• Epilepsy and/or compromised central nervous system (CNS) function
• Significant cardiovascular dysfunction within the previous 6 months before the study starts (eg, angina, congestive heart failure, recent myocardial infarction, moderate or severe hypertension, significant arrhythmia)
• Hemoglobinopathies
• Poorly controlled diabetes mellitus
• Chronic pulmonary disease (eg, chronic obstructive pulmonary disease)
• Clinical gout
• Hypersensitivity to interferons or any component of the drug

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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150 participants in 2 patient groups

Arm A - PegIntron

Experimental group

Description:

Participants randomized to Arm A received peginterferon α-2b (PegIntron), 50 μg, weekly, subcutaneously (SC), for a period of 3 years.

Treatment:

Biological: Peginterferon alfa-2b

Arm B - Control

Other group

Description:

Participants randomized to Arm B were under observation and received no treatment.

Treatment:

Other: Observation (no treatment)