A Study of Induction Dosing With Peginterferon Alfa-2a and Ribavirin in Participants With Chronic Hepatitis C (CHC) Genotype 1 Infection

Study Overview
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Brief Summary
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This study will evaluate the addition of a higher-dose induction treatment period with peginterferon (PEG-IFN) alfa-2a (Pegasys) and ribavirin prior to standard-dose treatment with PEG-IFN alfa-2a and ribavirin, compared to standard-dose treatment, in treatment-naive participants with CHC, genotype 1 infection.

Official Title
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A Phase IV, Randomised, Multicentre, Efficacy and Safety Study Examining the Effect of Induction Dosing With the Combination of Peginterferon Alfa-2a and Ribavirin in Patients With Chronic Hepatitis C Infected With Hepatitis C Genotype 1

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: PEG-IFN alfa-2a
* Drug: Ribavirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of chronic CHC, genotype 1 Chronic liver disease consistent with CHC on a biopsy sample obtained within the previous 36 months as judged by a local pathologist (all countries except Australia) Infection with Hepatitis C virus (Australian sites only had to meet Section 100 criteria for treatment with PEG-IFN alfa-2a plus ribavirin) Compensated liver disease Naive to interferon-based therapy for CHC infection Exclusion Criteria: Systemic antiviral, antineoplastic, or immunomodulatory treatment within 6 months of study drug Coinfection with active hepatitis A or B virus, or with human immunodeficiency virus (HIV) Chronic liver disease other than CHC infection

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PEG-IFN alfa-2a+Ribavirin - Induction Treatment<br>Participants will receive 12 weeks of induction therapy with PEG-IFN alfa-2a (Pegasys), 360 micrograms (mcg) subcutaneous (SC) once weekly, along with ribavirin, 1000 or 1200 milligrams (mg) orally daily in divided doses. Thereafter, the dose of PEG-IFN alfa-2a will be reduced to 180 mcg SC once weekly and the ribavirin dose maintained for the remaining 36 weeks of treatment. | Drug: PEG-IFN alfa-2a<br>* PEG-IFN alfa-2a will be administered once weekly for 48 weeks, at doses specified in respective arms.<br>* Other names: Pegasys;Drug: Ribavirin<br>* Ribavirin 1000 or 1200 mg orally daily in divided doses, with the dose determined based on body weight, for 48 weeks.<br>* Other names: Copegus;|
| Experimental: PEG-IFN alfa-2a+Ribavirin - Standard Treatment<br>Participants will receive 48 weeks of standard therapy with PEG-IFN alfa-2a, 180 mcg SC once weekly, along with ribavirin, 1000 or 1200 mg orally daily in divided doses. | Drug: PEG-IFN alfa-2a<br>* PEG-IFN alfa-2a will be administered once weekly for 48 weeks, at doses specified in respective arms.<br>* Other names: Pegasys;Drug: Ribavirin<br>* Ribavirin 1000 or 1200 mg orally daily in divided doses, with the dose determined based on body weight, 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 |
| --- | --- | --- |
| Percentage of Participants With Sustained Virological Response According to Scheduled Treatment Period | Sustained virological response was calculated as the percentage of participants with undetectable (less than [<] 15 international units per milliliter [IU/mL]) hepatitis C virus (HCV) ribonucleic acid (RNA) as measured by the Roche TaqMan HCV Test 24 weeks after completion of the scheduled 48-week treatment period. | Week 72 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With End-of-Treatment Virological Response According to Scheduled Treatment Period | Virological response at the end of the scheduled treatment period was defined as the percentage of participants with undetectable (<15 IU/mL) HCV RNA as measured by the Roche TaqMan HCV Test at Week 48. | Weeks 48 | 
| Percentage of Participants With Virological Responses Over Time | Virological response was defined as undetectable HCV RNA (<15 IU/mL) as measured by the Roche TaqMan HCV Test. Participants without HCV RNA measurements at a study week are considered non responders at that study week. | Weeks 4, 8, 12, and 24 | 
| Percentage of Participants With Relapse of End-of-treatment Virological Response | Relapse was determined based on virological response at the actual end of treatment and was calculated by dividing the number of participants who achieved a virological response at end of treatment but later had detectable HCV RNA at the last assessment post-treatment by the number of participants with a virological response at end of treatment, defined as undetectable HCV RNA (<15 IU/mL). Participants who achieved a virological response at end of treatment but did not have any HCV RNA assessment during follow-up were excluded and were not considered as having relapsed. However, if no assessment was available within the end of-treatment time window but the participant had a sustained virological response according to the actual treatment period, backward imputation was used and the participant was considered to have achieved an end-of-treatment virological response in the analysis. | Actual end of treatment (Week 48) up to last follow up (maximum up to Week 72) | 
| Percentage of Participants With Predictive Values of Virological Response for Sustained Virological Response | The ability of virological responses to predict sustained virological response according to the scheduled treatment periods was assessed in terms of positive predictive value (PPV) and negative predictive value (NPV). The PPV indicates probability of achievement of viral suppression (undetectable HCV RNA) for achieving a sustained virological response and the NPV indicates probability of not achieving viral suppression for not achieving a sustained virological response. The PPV at Week 4 or 12 was calculated as the number of participants who achieved viral suppression both at Week 4 or 12 and at Week 72 divided by the number of participants who achieved viral suppression at Week 4 or 12, multiplied by 100. The NPV at Week 4 or 12 was calculated as the number of participants who failed to achieve viral suppression at Week 4 or 12 and at Week 72 divided by the number of participants who failed to achieve viral suppression at Week 4 or 12, multiplied by 100. | Weeks 4, 12, and 72 | 
| Change From Baseline in Log10 HCV RNA Values | The mean decrease in log10 HCV RNA levels from baseline was assessed in both the induction group and the standard group. | Baseline, Weeks 4, 8, 12, 24, and at end of treatment (EoT) (maximum up to Week 48) |