Evaluation of Peginterferon Alfa-2b Monotherapy and Combination With Ribavirin in Participants With Acute Hepatitis C (P03552/MK-4031-137)

Phase 3

Completed

• Conditions: Hepatitis C
• Interventions: Biological: Pegylated interferon alfa-2b; Drug: Ribavirin

• Registration Number: NCT00686517
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

The objective of this study is to evaluate the efficacy of three regimens of pegylated interferon-alfa 2b (PEG-IFN) either as monotherapy or in combination with ribavirin in participants with acute hepatitis C. After 12 weeks of observation from disease onset, participants will receive one of the following regimens: (1) a 24-week course of PEG-IFN monotherapy (PEG-IFN 24); or (2) a 12-week course of PEG-IFN monotherapy (PEG-IFN-12); or (3) a 12-week course of PEG-IFN in combination with ribavirin (PEG-IFN + RVB 12). After the treatment period, participants will enter a 12-month follow-up.

Detailed Description

Not available

Study Timeline

• Study Start: 2003-12
• Study First Submitted: 2008-05-27
• Study First Submitted QC: 2008-05-27
• Study First Posted: 2008-05-30
• Primary Completion: 2010-12
• Study Completion: 2010-12
• Results First Submitted: 2011-12-22
• Results First Submitted QC: 2011-12-22
• Results First Posted: 2012-01-31
• Status Verified: 2017-03
• Last Update Submitted: 2017-03-08
• Last Update Posted: 2017-04-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 130

Inclusion Criteria

• Diagnosed with acute hepatitis C virus (HCV).
• Normal and Elevated serum alanine transferase (ALT) levels
• Positive serum HCV-RNA.
• Aged between 18 and 65 years.
• Negative urine or serum pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of the drug. Additionally, all fertile males with partners of childbearing age and females must be using reliable contraception during the study and additionally for participants treated with ribavirin, for 6 months (for woman) and 7 months (for man and his partner) after treatment completion

Exclusion Criteria

• Liver disease unrelated to HCV infection
• Hemoglobin (Hgb) <12g/dL in women and <13g/dL in men; white blood cells (WBC) <3,000/uL; platelets (PLTs) <100,000/ul
• Women with ongoing pregnancy or who are breast feeding
• History of severe psychiatric disease, especially depression
• History of neurologic disease, especially epilepsy
• History or evidence of symptoms of severe cardiac, gastrointestinal and kidney disease
• Positive anti-Human Immunodeficiency Virus (HIV) antibodies
• Positive anti-nuclear antibodies (ANA) and/or Anti-Smooth Muscle Antibody (ASMA) (>1/80)
• Positive Hepatitis B surface antigen (HBsAg)
• History of having received any systemic anti-neoplastic or immunomodulatory treatment in the previous 6 months
• History or other evidence of severe illness or any other conditions which would make the participants, in the opinion of investigator, unsuitable for the study (active drug addict except those under methadone treatment, thalassemic, dyalized included)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PEG-IFN 24	Pegylated interferon alfa-2b	pegylated interferon alpha-2b 1.5 ug/kg/week for 24 weeks
PEG-IFN 12	Pegylated interferon alfa-2b	pegylated interferon alpha-2b 1.5 ug/kg/week for 12 weeks
PEG-IFN + RVB 12	Pegylated interferon alfa-2b	pegylated interferon alpha-2b 1.5 ug/kg/week in combination with ribavirin at the dose of 10.6 mg/kg/day for 12 weeks
PEG-IFN + RVB 12	Ribavirin	pegylated interferon alpha-2b 1.5 ug/kg/week in combination with ribavirin at the dose of 10.6 mg/kg/day for 12 weeks

Primary Outcome Measures

Name	Time	Method
Number of Participants With Sustained Response (SR) at the End of the 6-month Follow-up Period	Evaluated at the end of 6 months	SR was defined as serum Hepatitis C Virus (HCV RNA) level at the end of 6-month follow-up below 15 IU/mL.

Secondary Outcome Measures

Name	Time	Method
Virologic Response at the End of Treatment Follow-up (ETR)	At the end of treatment (either 12 weeks or 24 weeks depending on randomization).	ETR was achieved if serum HCV RNA level at the end of 12 or 24 weeks; treatment (depending on treatment arm) was \<15 IU/mL.
Virologic Response at 12 Months Post-treatment Follow-up (Long-term Response, [LTR]).	At 12 months post-treatment (treatment period either 12 weeks or 24 weeks depending on randomization).	LTR was obtained if serum HCV RNA level at the end of 12-month follow-up was \<15 IU/mL.
Number of Participants With Rapid Virologic Response (RVR)	Evaluated at 2 and 4 weeks of treatment	Participants were considered to have RVR if serum HCV RNA level at 2 or 4; weeks of treatment was below the cut off value of the referring local; laboratory of each participating site.
Number of Participants Presenting With Alanine Transferase (ALT) Level Normalization	Evaluated at end of treatment (either 12 weeks or 24 weeks, depending on randomization), at 6-month follow-up visit, or at 12-month follow-up visit.	ALT normalization was used as a measure of biochemical response to treatment. ALT levels were assessed at each study visit by the local laboratory, and efficacy measurements at the end of treatment, at 6 and 12 months post treatment follow-up were reported.
Number of Peripheral Blood Mononuclear Cells (PBMCs)	Treatment Weeks 2, 4, 8, and 12	Cellular Differentiation Cluster Antigen 8-Positive (CD8+) PBMCs were measured at randomization, Treatment Weeks 2, 4, 8, and 12.