Efficacy and Safety of Peg-Interferon Alpha-2a Plus Ribavirin in Genotype 1 Chronic Hepatitis C Participants Co-Infected With Human Immunodeficiency Virus

Study Overview
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Brief Summary
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This randomized, multi-center, Phase IV, comparative study will assess the efficacy and safety of combined peg-interferon alpha-2a (Peg-IFN-Alpha-2A) and ribavirin therapy for 48 or 72 weeks of treatment and 24 weeks of follow-up in participants with Genotype 1 chronic hepatitis C (CHC), co-infected with human immunodeficiency virus type 1 (HIV-1).

Official Title
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Randomized, Multi-Center, Phase IV, Comparative Study to Assess the Efficacy and Safety of Combined Peg-Interferon Alpha-2a (40 kD) With Ribavirin Combined Therapy for 48 or 72 Weeks of Treatment and 24 Weeks of Follow-Up in Patients With Chronic Hepatitis C, Genotype 1, Co-Infected With Human Immunodeficiency Virus

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: Peg-Interferon Alpha-2A
* Drug: Ribavirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Serological evidence of chronic hepatitis C infection by anti-hepatitis C virus (HCV) test Detectable HCV-ribonucleic acid (RNA) plasma level testing by Roche AMPLICOR HCV (<50 International Units per milliliter [IU/mL]) (qualitative test) Chronic liver disease consistent with infection of CHC Compensated liver disease (Child-Pugh Grade A) Serological evidence of infection by HIV-1 test, anti-HIV-1 or HIV-1 RNA detection Negative pregnancy urine or blood test (for women in childbearing age); additionally, all men and women of childbearing potential must agree to use two effective forms of contraception during the treatment and during the 6 months after the end of treatment Exclusion Criteria: Pregnant or nursing women and male partners of pregnant women Prior therapy with interferon (IFN) or ribavirin and any investigational medication less than or equal to (</=) 6 weeks before the first dose of the study drug History or other evidence of a medical condition associated with chronic liver disease further than HCV Active opportunistic infection associated with HIV and / or cancer requiring systemic therapy History of any other significant illness which in the investigator's opinion, could result in the participant's inability to meet the Protocol requirements

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-Alpha-2A+Ribavirin - 48 Weeks<br>Participants will receive Peg-IFN-Alpha-2A and ribavirin for 48 weeks. | Drug: Peg-Interferon Alpha-2A<br>* Peg-IFN-Alpha-2A will be administered at 180 micrograms (mcg) once weekly via subcutaneous injection.<br>* Other names: Pegasys, Peg-IFN-Alpha-2A;Drug: Ribavirin<br>* Ribavirin will be administered as either 1000 milligrams (mg) (2*200 mg tablets in morning and 3*200 mg tablets in evening) for participants weighing less than (<) 75 kilograms (kg) or as 1200 mg (3*200 mg tablets in morning and 3*200 mg tablets in evening) for participants weighing greater than or equal to (>/=) 75 kg.<br>|
| Active Comparator: Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks<br>Participants will receive Peg-IFN-Alpha-2A and ribavirin for 72 weeks. | Drug: Peg-Interferon Alpha-2A<br>* Peg-IFN-Alpha-2A will be administered at 180 micrograms (mcg) once weekly via subcutaneous injection.<br>* Other names: Pegasys, Peg-IFN-Alpha-2A;Drug: Ribavirin<br>* Ribavirin will be administered as either 1000 milligrams (mg) (2*200 mg tablets in morning and 3*200 mg tablets in evening) for participants weighing less than (<) 75 kilograms (kg) or as 1200 mg (3*200 mg tablets in morning and 3*200 mg tablets in evening) for participants weighing greater than or equal to (>/=) 75 kg.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virologic Response (SVR) | SVR was defined as having un-detectable hepatitis C virus (HCV) ribonucleic acid (RNA) levels 24 weeks after completion of study treatment. HCV RNA levels were measured using Roche COBAS AMPLICOR HCV Test (limit of detection: 50 International Units per milliliter [IU/mL]). Participants with detectable HCV RNA or without measurement at the end of the 24 week after completion of study treatment were considered as non-responders. | 24 weeks after completion of study treatment (up to Week 72 for Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks arm and up to Week 96 for Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks arm) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Undetectable HCV RNA | HCV RNA levels were measured using Roche COBAS AMPLICOR HCV Test (limit of detection: 50 IU/mL). Data for this outcome measure was to be reported up to end of treatment visit (Week 48 for 'Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks' arm and Week 72 for 'Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks' arm). | For Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks arm: Weeks 4, 12, 24, and 48; for Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks arm: Weeks 4, 12, 24, 48, and 72 | 
| Percentage of Participants With Undetectable HCV RNA 12 Weeks After the Last Dose of Peg-IFN-Alpha-2A | HCV RNA levels were measured using Roche COBAS AMPLICOR HCV Test (limit of detection: 50 IU/mL). Participants with detectable HCV RNA or without measurement at the end of 12 weeks after the last dose of Peg-IFN-Alpha-2A were considered as non-responders. | 12 weeks after the last dose of Peg-IFN-Alpha-2A (up to Week 60 for Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks arm and up to Week 84 for Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks arm) | 
| Percentage of Participants Without SVR Among Participants With Undetectable HCV RNA at the End of Treatment | SVR was defined as having undetectable HCV RNA levels 24 weeks after completion of study treatment. HCV RNA levels were measured using Roche COBAS AMPLICOR HCV Test (limit of detection: 50 IU/mL). Percentage of participants without SVR among participants with undetectable HCV RNA at the end of treatment was reported (end of treatment = Week 48 for Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks arm and Week 72 for Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks arm). | 24 weeks after completion of study treatment (up to Week 72 for Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks arm and up to Week 96 for Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks arm) | 
| Serum Human Immunodeficiency Virus (HIV) RNA Levels | HIV RNA levels were measured using Roche AMPLICOR MONITOR HIV-1 Test (limit of detection: 400 HIV-1 RNA copies/mL). Data for this outcome measure was to be reported up to 24 weeks after end of treatment visit (Week 72 for 'Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks' arm and Week 96 for 'Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks' arm). | For Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks arm: Weeks 4, 12, 24, 48, and 72; for Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks arm: Weeks 4, 12, 24, 48, 72, and 96 | 
| Change From Baseline in Cluster of Differentiation (CD) 4 (CD4) Cell Counts at Weeks 4, 12, 24, 48, 72, and 96 | Data for this outcome measure was to be reported up to 24 weeks after end of treatment visit (Week 72 for 'Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks' arm and Week 96 for 'Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks' arm). | For Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks arm: Baseline, Weeks 4, 12, 24, 48, and 72; for Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks arm: Baseline, Weeks 4, 12, 24, 48, 72, and 96 | 
| Change From Baseline in CD4/CD8 Ratio at Weeks 4, 12, 24, 48, 72, and 96 | Data for this outcome measure was to be reported up to 24 weeks after end of treatment visit (Week 72 for 'Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks' arm and Week 96 for 'Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks' arm). | For Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks arm: Baseline, Weeks 4, 12, 24, 48, and 72; for Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks arm: Baseline, Weeks 4, 12, 24, 48, 72, and 96 | 
| Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | ALT levels were classified as: Normal Limit (NL) (as per laboratory standard), >1-2 Upper Normal Limit (ULN), >2-5 ULN, >5-10 ULN, and >10 ULN. Percentage of participants in each of these ALT level categories was reported. Data for this outcome measure was to be reported up to 24 weeks after end of treatment visit (Week 72 for 'Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks' arm and Week 96 for 'Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks' arm). | For Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks arm: Weeks 4, 12, 24, 48, and 72; for Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks arm: Weeks 4, 12, 24, 48, 72, and 96 |