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

Study Overview
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Brief Summary
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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.

Official Title
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An Open, Randomized, Multicentre Trial to Evaluate Efficacy and Safety of a 24-week Course of PEG-Interferon Alpha-2b Versus a 12-week Course of PEG-Interferon Alpha-2b Alone or Plus Ribavirin in Patients With Acute Hepatitis C

Conditions
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Hepatitis C

Intervention / Treatment
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* Biological: Pegylated interferon alfa-2b
* Drug: Ribavirin


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PEG-IFN 24<br>pegylated interferon alpha-2b 1.5 ug/kg/week for 24 weeks | Biological: Pegylated interferon alfa-2b<br>* 1.5 ug/kg/week SC for 12 or 24 weeks<br>* Other names: SCH 54031, PegIntron;|
| Experimental: PEG-IFN 12<br>pegylated interferon alpha-2b 1.5 ug/kg/week for 12 weeks | Biological: Pegylated interferon alfa-2b<br>* 1.5 ug/kg/week SC for 12 or 24 weeks<br>* Other names: SCH 54031, PegIntron;|
| Experimental: PEG-IFN + RVB 12<br>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 | Biological: Pegylated interferon alfa-2b<br>* 1.5 ug/kg/week SC for 12 or 24 weeks<br>* Other names: SCH 54031, PegIntron;Drug: Ribavirin<br>* Ribavirin at the dose of 10.6 mg/kg/day for 12 weeks<br>* Other names: SCH 18908, Rebetol;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Virologic Response at the End of Treatment Follow-up (ETR) | 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. | At the end of treatment (either 12 weeks or 24 weeks depending on randomization). | 
| Virologic Response at 12 Months Post-treatment Follow-up (Long-term Response, [LTR]). | LTR was obtained if serum HCV RNA level at the end of 12-month follow-up was <15 IU/mL. | At 12 months post-treatment (treatment period either 12 weeks or 24 weeks depending on randomization). | 
| Number of Participants Presenting With Alanine Transferase (ALT) Level Normalization | 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. | 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. | 
| Number of Participants With Rapid Virologic Response (RVR) | 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. | Evaluated at 2 and 4 weeks of treatment | 
| Number of Peripheral Blood Mononuclear Cells (PBMCs) | Cellular Differentiation Cluster Antigen 8-Positive (CD8+) PBMCs were measured at randomization, Treatment Weeks 2, 4, 8, and 12. | Treatment Weeks 2, 4, 8, and 12 |