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

NCT00759109 | Completed Phase 3 Results

• 1 other identifier: P02733
• Study Type: interventional
• Target: 150
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Carcinoma, Hepatocellular

Outcome Measures

Primary Outcomes (1)

• Number of Participants With the Development of Hepatocellular Carcinoma (HCC)

  Participants were tested for focal lesions by liver ultrasound and for AFP levels every 6 months the during study (treatment and follow-up). The development of hepatocellular carcinoma was determined by: 1. the appearance of a focal lesion detected by liver ultrasound with metastases confirmed by fine needle biopsy, or 2. the appearance of a focal lesion detected by ultrasound + alphafetoprotein (AFP) levels in blood \>400 ng/mL.

  During 3 years of treatment and 2 years of follow-up

Secondary Outcomes (4)

• Number of Participants With Development of Hepatic Decompensation

  Baseline, During 3 years of treatment and 2 years of follow-up

• Survival Time of Participants

  During 3 years of treatment and 2 years of follow-up

• Number of Patients With a Virological Response Rate

  Baseline and every year during 3 years of treatment

• Change in the Proliferating Cell Nuclear Antigen Labeling Index (PCNA-LI)

  Baseline and at 18 months of treatment

Other Outcomes (1)

• Proliferating Cell Nuclear Antigen Labeling Index (PCNA-LI) at Baseline

  Baseline

Study Arms (2)

Arm A - PegIntron

EXPERIMENTAL

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

Biological: Peginterferon alfa-2b

Arm B - Control

OTHER

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

Other: Observation (no treatment)

Interventions

Peginterferon alfa-2b BIOLOGICAL

Peginterferon alfa-2b, 50 μg, weekly, SC, for a period of 3 years.

Also known as: PegIntron, Pegylated Alfa-2b, SCH 054031

Arm A - PegIntron

Observation (no treatment) OTHER

No treatment was given to participants enrolled in the control arm (Arm B).

Arm B - Control

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

peginterferon alfa-2b; Observation

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Methods; Investigative Techniques

Results Point of Contact

• Title: Senior Vice President,Global Clinical Development
• Organization: Merck Sharp and Dohme Corp.

ClinicalTrialsDisclosure@merck.com

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2008
• First Posted: September 25, 2008
• Study Start: March 1, 2002
• Primary Completion: November 1, 2009
• Study Completion: November 1, 2009
• Last Updated: April 7, 2017
• Results First Posted: April 18, 2011

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will share