REPEAT Study - A Study of PEGASYS (Peginterferon Alfa-2a (40KD)) Therapy in Combination With COPEGUS (Ribavirin) in Patients With Chronic Hepatitis C (CHC) Who Did Not Respond to Previous PegIntron (Peginterferon Alfa-2b (12KD))/Ribavirin Combination Therapy

Study Overview
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Brief Summary
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This 4 arm study is designed for patients with CHC who have not responded to peginterferon alfa-2b (12KD)/ribavirin combination therapy. In these patients, the effects of lengthening the duration of treatment, as well as including an initial 12-week period of high-dose PEGASYS (360 micrograms sc), are compared with the standard combination therapy of PEGASYS (180 micrograms sc) and ribavirin (1000-1200mg po). The anticipated time on study treatment is 1-2 years and the target sample size is 500+ individuals.

Official Title
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A Randomized, Open-label Study of the Effect of PEGASYS Combined With Ribavirin on Sustained Virologic Response in Patients With Chronic Hepatitis C Who Did Not Respond to Previous Pegintron/Ribavirin Combination Therapy

Conditions
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Hepatitis C, Chronic

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients >=18 years of age; CHC infection; liver biopsy (in <24 calendar months of first dose), with results consistent with CHC infection; use of 2 forms of contraception during study and 6 months after the study in both men and women; Lack of response to previous treatment with peginterferon alfa-2b (12KD)/ribavirin combination therapy given for >=12 weeks. Exclusion Criteria: women who are pregnant or breastfeeding; male partners of women who are pregnant; conditions associated with decompensated liver disease; 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: Ribavirin<br>* 1000/1200mg po daily for 72 weeks<br>Drug: peginterferon alfa-2a [Pegasys]<br>* 360 micrograms sc weekly for 12 weeks, followed by 180 micrograms sc weekly for 60 weeks<br>|
| Experimental: 2<br> | Drug: Ribavirin<br>* 1000/1200mg po daily for 48 weeks<br>Drug: peginterferon alfa-2a [Pegasys]<br>* 360 micrograms sc weekly for 12 weeks, followed by 180 micrograms sc weekly for 36 weeks.<br>|
| Experimental: 3<br> | Drug: Ribavirin<br>* 1000/1200mg po daily for 72 weeks<br>Drug: peginterferon alfa-2a [Pegasys]<br>* 180 micrograms sc weekly for 72 weeks<br>|
| Active Comparator: 4<br> | Drug: Ribavirin<br>* 1000/1200mg po daily for 48 weeks<br>Drug: peginterferon alfa-2a [Pegasys]<br>* 180 micrograms sc weekly for 48 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Sustained Virological Response Rate | Sustained Virological Response (SVR) was defined as the percentage of participants with a undetectable hepatitis C virus- ribonucleic acid (HCV RNA) 24 weeks after the end of the treatment period (defined as a single last HCV RNA < 50 International Units Per Millilitre (IU/mL) measured >= 20 weeks after treatment end, ie, >=140 days after treatment end. | Up to 72 weeks (Group A) and 48 weeks (Group D) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Sustained Virological Response (Groups A + B vs Groups C + D) | SVR was defined as the percentage of participants with a undetectable hepatitis C virus- ribonucleic acid (HCV RNA) 24 weeks after the end of the treatment period (defined as a single last HCV RNA < 50 International Units Per Millilitre (IU/mL) measured >= 20 weeks after treatment end, ie, >=140 days after treatment end. | At Week 48 and Week 72 | 
| Number of Participants With Sustained Virological Response (Groups A + C vs Groups B + D) | SVR was defined as the percentage of participants with a undetectable hepatitis C virus- ribonucleic acid (HCV RNA) 24 weeks after the end of the treatment period (defined as a single last HCV RNA < 50 International Units Per Millilitre (IU/mL) measured >= 20 weeks after treatment end, ie, >=140 days after treatment end. | At Week 48 and Week 72 | 
| Percentage of Participants With Undetectable HCV-RNA | The percentage of participants with a undetectable HCV RNA 24 weeks after the end of the treatment period (defined as a single last HCV RNA < 50 IU/mL measured >= 20 weeks after treatment end, ie, >=140 days after treatment end) are reported. End-of-treatment (EOT) virological response is defined as last HCV RNA measurement that is not detectable (<50 IU/mL) at study day of last dose of study medication (+/- 28 days). | At Week 12, 24, 48 and EOT | 
| Percentage of Participants With >=2log Drop in HCV-RNA | Reduction in HCV-RNA titers of at least 2 log10 after 12/24 weeks of study treatment (i.e. 99% reduction of viral load) was analyzed. Percentage of participants with at least a 2 log10 drop of HCV-RNA at study week 12 and 24 (lower limit of quantitation 600 IU/mL) as compared to baseline or non-detectable HCV-RNA (lower limit of detection 50 IU/mL) were reported. | At Week 12 and 24 | 
| Change From Baseline in Reduction of HCV Viremia (Groups A + B vs Groups C + D) | The mean change from baseline in HCV RNA level (reduction in viral load) at Week 12 and 24 were determined. HCV RNA result were not detectable (<50 IU/ML) and not quantifiable (<600 IU/ML). Baseline value were assessed on Day 1 before the administration of the first dose of study drug. | At Week 12 and 24 | 
| Percentage of Participants With Maintenance of Actual End-of-Treatment Virological Response | Maintenance of end-of-treatment virological response was assessed based on all participants treated and according to the actual treatment period (backward imputation method). The percentage of participants who maintained their end-of-treatment virological response was determined. Maintenance of actual end-of-treatment virological response was calculated by dividing the number of participants with a virological response both at the end of the actual untreated follow-up period and at the end of the actual treatment period by the number of participants with a virological response at the actual end of treatment. | Week 96 (Group A and C) and Week 72 (Group B and D) | 
| Percentage of Participants With Relapse After End of Treatment | The percentage of participants who relapsed (loss of response) after having achieved a virological response at the end of treatment was determined. | Week 96 (Group A and C) and Week 72 (Group B and D) |