A Study of Combination Therapy With PEGASYS (Pegylated Interferon Alfa-2a (40KD)) and Copegus (Ribavirin) in Patients With Chronic Hepatitis C Genotype 2 or 3 Who Do Not Achieve a Rapid Viral Response

Study Overview
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Brief Summary
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This study will evaluate the efficacy and safety of peginterferon alfa-2a 40KD + ribavirin combination therapy given for 24 weeks versus 48 weeks in patients with chronic hepatitis C, genotype 2/3.

Detailed Description
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During a pre-study run-in phase patients with chronic hepatitis C genotype 2/3, who had started therapy with PEG-IFN alfa-2a plus ribavirin according to local standard of care and did not achieve a rapid viral response (RVR) (defined as Hepatitis C virus (HCV) RNA <15 IU/mL at Week 4 of treatment measured with the Roche COBAS AmpliPrep / COBAS TaqMan® HCV Test) were eligible for the study and entered the screening phase between treatment Week 4 and 8 as soon as the result of the Week 4 HCV RNA test was available. Eligible patients entered the study and continued with the dose regimens of PEG-IFN alfa-2a and ribavirin they were taking prior to enrolment into the trial up to Week 24 of treatment. Patients who achieved at least a 2-log10 drop of HCV RNA at Week 12 (as compared to HCV RNA levels prior to treatment initiation) or had HCV RNA <15 IU/mL, and who were still taking study medication at treatment Week 24, were randomized at treatment Week 24 to one of the two study groups. Upon randomization, participants either stopped treatment (equaling 24 weeks of treatment) or continued treatment for another 24 weeks (equaling 48 weeks of treatment). A treatment free follow-up period of 24 weeks (for participants in the 48-week treatment group) or 48 weeks (participants in the 24-week treatment group) completed the study.

Official Title
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A Randomized, Open-label Study of the Effects of 24 vs 48 Weeks of Combination Therapy With PEGASYS (Peginterferon Alfa-2a 40KD) Plus COPEGUS (Ribavirin) on Sustained Virological Response in Patients With Chronic Hepatitis C, Genotype 2 or 3 Who do Not Achieve a Rapid Viral Response

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* 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; serological evidence of chronic hepatitis C (CHC); CHC genotype 2 or 3; receiving PEGASYS + Copegus according to local standard of care and no rapid viral response (RVR); compensated liver disease. Exclusion Criteria: pegylated interferon, standard interferon or ribavirin therapy at any time prior to initiation of current therapy with PEGASYS + Copegus; coinfection with hepatitis A or B, or human immunodeficiency virus (HIV); history or other evidence of decompensated liver disease.

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: PEG-IFN alfa-2a + Ribavirin for 24 weeks<br>After 24 weeks of treatment with pegylated interferon alfa-2a (PEG-IFN alfa-2a) 180 μg/week plus ribavirin 800-1200 mg/day participants who achieved at least a 2-log10 drop of hepatitis C virus (HCV) ribonucleic acid (RNA) at Week 12 (as compared to HCV RNA levels prior to treatment initiation) or had HCV RNA <15 IU/mL, and who were still taking study medication at treatment Week 24 were randomized into the study, at which time treatment was stopped. Participants were followed for an additional 48 weeks during the treatment-free follow-up period. | Drug: peginterferon alfa-2a<br> <br> * Other names: PEG-IFN alfa-2a;Drug: Ribavirin<br> <br> * Other names: Copegus®;|
| Active Comparator: PEG-IFN alfa-2a + Ribavirin for 48 weeks<br>After 24 weeks of treatment with PEG-IFN alfa-2a 180 μg/week plus ribavirin 800-1200 mg/day participants who achieved at least a 2-log10 drop of HCV RNA at Week 12 (as compared to HCV RNA levels prior to treatment initiation) or had HCV RNA <15 IU/mL, and who were still taking study medication at treatment Week 24 were randomized into the study, and continued treatment for another 24 weeks (for a total of 48 weeks of treatment). Participants were followed for an additional 24 weeks during the treatment-free follow-up period. | Drug: peginterferon alfa-2a<br> <br> * Other names: PEG-IFN alfa-2a;Drug: Ribavirin<br> <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 a Sustained Virologic Response 24 Weeks After Scheduled Completion of Treatment | Sustained virological response (SVR) is defined as a single last HCV RNA measurement <15 IU/ml (measured using the Roche COBAS AmpliPrep / COBAS TaqMan HCV Test) 24 weeks after scheduled treatment completion, defined as Week 44 or later for participants randomized to the 24-week treatment period or Week 68 or later for participants randomized to the 48-week treatment period. Participants without measurements at the end of the 24-week untreated follow-up period were considered non-responders in the analysis. | 24 weeks after scheduled treatment completion (approximately Week 48 for participants in the 24-week treatment group and Week 72 for participants in the 48-week treatment group. | 
| Percentage of Participants With a Sustained Virologic Response 24 Weeks After Actual End of Treatment | Sustained virological response (SVR) is defined as a single last HCV RNA measurement <15 IU/ml (measured using the Roche COBAS AmpliPrep / COBAS TaqMan HCV Test) at 24 weeks after actual end of study treatment. For participants in the 48-week treatment group who stopped study treatment prior to Week 48 for any reason, the HCV RNA measurements 24 weeks after actual end of treatment were used in the analysis. Participants without a 24-week post treatment measurement are considered non-responders. | 24 weeks after actual end of treatment (range from Week 48 to Week 72). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Virological Response 72 Weeks After Treatment Initiation | Virological response 72 weeks after treatment initiation is defined as the percentage of participants with HCV RNA <15 IU/mL as measured by the Roche COBAS AmpliPrep / COBAS TaqMan® HCV Test at 48 weeks post completion of the 24 week treatment period and 24 weeks post completion of the 48 week treatment period. Participants without Week 72 measurements were considered non-responders in the analysis. | Week 72 | 
| Percentage of Participants With Virological Response at End of Treatment | Virological response at the end of treatment was defined as the percentage of participants with HCV RNA <15 IU/mL as measured by the Roche COBAS AmpliPrep / COBAS TaqMan® HCV Test after the last dose of study medication. | End of Treatment (Week 24 and Week 48 for each treatment group respectively). | 
| Percentage of Participants With Virological Relapse | Virological relapse defined as the percentage of participants with a virological response at end of treatment but who did not have a sustained virological response 24 weeks after the end of treatment. Virological response at end of treatment is defined as a single last HCV RNA measurement <15 IU/ml measured using the Roche COBAS AmpliPrep / COBAS TaqMan HCV Test at the day of last dose of study medication. Sustained virological response 24 weeks after the actual treatment end (SVR24) is defined as a single last HCV RNA measurement <15 IU/ml at least 20 weeks after treatment end. | End of treatment (Weeks 24 or 48) and 24 weeks after the end of treatment (weeks 48 and 72 in each treatment group respectively). | 
| Percentage of Participants With a Sustained Virologic Response 12 Weeks After Actual End of Treatment | Sustained virological response (SVR) is defined as a single last HCV RNA measurement <15 IU/ml (measured using the Roche COBAS AmpliPrep / COBAS TaqMan HCV Test) at 12 weeks after actual end of study treatment. For participants in the 48-week treatment group who stopped study treatment prior to Week 48 for any reason, the HCV RNA measurements 12 weeks after actual end of treatment were used in the analysis. Participants without a 12-week post treatment measurement are considered non-responders. | 12 weeks after actual end of treatment (range from Week 36 to Week 60) | 
| Number of Participants With Adverse Events (AEs) | An AE was defined as a sign or symptom, including intercurrent illness, that occurred during the course of the clinical study after treatment had started. A related AE is an event assessed by the Investigator to be remotely, possibly, or probably related to study treatment according to criteria provided in the protocol. A severe AE was an event graded by the Investigator as incapacitating with inability to work or perform normal daily activity. A serious AE (SAE) was defined as any experience that suggests a significant hazard, contraindication, side effect or precaution. This includes any experience which was fatal; was life-threatening; required inpatient hospitalization or prolongation of an existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/ birth defect; was medically significant or required intervention to prevent one or other of the outcomes listed above. | From Week 1 through Week 72. |