A Study of Induction Dosing With PEGASYS (Peginterferon Alfa-2a [40KD]) Plus Copegus in Treatment-Naive Patients With Chronic Hepatitis C

Study Overview
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Brief Summary
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This 4-arm study will compare the efficacy and safety of PEGASYS induction and maintenance dosing, versus standard fixed dosing in combination with Copegus, and the efficacy and safety of higher dose versus standard dose Copegus in combination with PEGASYS. Patients with chronic hepatitis C (CHC) genotype 1 infection of high viral titer, and baseline body weight ≥85 kg, will be randomized to one of 4 groups, to receive one of the following: a) PEGASYS 180 µg subcutaneously (sc) weekly plus Copegus 1200 mg orally (po) daily; b) PEGASYS 180 µg sc weekly plus Copegus 1400-1600 mg po daily; c)PEGASYS 360 µg sc weekly (induction) followed by 180 µg sc weekly (maintenance) plus Copegus 1200 mg po daily; or d) PEGASYS 360 µg sc weekly (induction) followed by 180 µg sc weekly (maintenance) plus Copegus 1400-1600 mg po daily. Following 48 weeks treatment, there will be a 24-week period of treatment-free follow-up. The anticipated time on study treatment is 3-12 months, and the target sample size is 500+ individuals.

Official Title
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Randomized, Multicenter, Double-blinded, Phase IV Study Evaluating the Efficacy (as Measured by Sustained Virological Response) and Safety of 360 μg Induction Dosing of Pegasys® in Combination With Higher Copegus® Doses in Treatment-naïve Patients With Chronic Hepatitis C Genotype 1 Virus Infection of High Viral Titer and Baseline Body Weight Greater Than or Equal to 85 kg

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: peginterferon alfa-2a
* Drug: Ribavirin
* Drug: peginterferon alfa-2a
* Drug: Ribavirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients, ≥18 years of age CHC infection, genotype 1 Hepatitis C virus (HCV) RNA ≥400,000 IU/mL Baseline body weight ≥85 kg Liver biopsy (within 24 months of first dose) with results consistent with CHC Exclusion Criteria: Previous treatment with interferon, ribavirin, viramidine, levovirin, HCV polymerase or protease inhibitors Other forms of liver disease, including liver cancer Human immunodeficiency virus infection

Ages Eligible for Study
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Minimum Age: 18 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: Factorial Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PEG-IFN 180 µg + Ribavirin 1200 mg<br> | Drug: peginterferon alfa-2a<br>* 180 µg sc weekly for 48 weeks<br>* Other names: Pegasys;Drug: Ribavirin<br>* 1200 mg po daily for 48 weeks<br>* Other names: Copegus;|
| Experimental: PEG-IFN 180 µg + Ribavirin 1400/1600 mg<br> | Drug: peginterferon alfa-2a<br>* 180 µg sc weekly for 48 weeks<br>* Other names: Pegasys;Drug: Ribavirin<br>* 1400-1600 mg po daily for 48 weeks<br>* Other names: Copegus;|
| Experimental: PEG-IFN 360/180 µg + Ribavirin 1200 mg<br> | Drug: Ribavirin<br>* 1200 mg po daily for 48 weeks<br>* Other names: Copegus;Drug: peginterferon alfa-2a<br>* 360 µg sc weekly decreasing to 180 µg sc weekly for 48 weeks<br>* Other names: Pegasys;|
| Experimental: PEG-IFN 360/180 µg + Ribavirin 1400/1600 mg<br> | Drug: peginterferon alfa-2a<br>* 360 µg sc weekly decreasing to 180 µg sc weekly for 48 weeks<br>* Other names: Pegasys;Drug: Ribavirin<br>* 1400-1600 mg po daily for 48 weeks<br>* Other names: Copegus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained Virological Response (SVR)-24 (Scheduled Treatment Period) | SVR-24 according to the scheduled treatment period was defined as the percentage of patients with undetectable HCV RNA at 24 weeks after completion of the treatment period (a single last HCV RNA PCR <15 IU/mL measured at or after week 68 (ie, on or after study day 477). | Week 72 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SVR-24 (Actual Treatment Period) | SVR-24 according to the actual treatment period was defined as the percentage of patients with undetectable HCV RNA at least 20 weeks after the last dose of study drug. | 24 weeks after end of treatment | 
| SVR-12 (Scheduled Treatment Period) | SVR-12 according to the scheduled treatment period was defined as the percentage of patients with undetectable HCV RNA at 12 weeks after the scheduled treatment period (a single last HCV RNA PCR <15 IU/mL measured at or after week 60). | 12 weeks after end of treatment | 
| SVR-12 (Actual Treatment Period) | SVR-12 according to the actual treatment period was defined as the percentage of patients with undetectable HCV RNA at least 12 weeks after the last dose of study drug. | 12 weeks after end of treatment |