Hepatitis C, Chronic
Conditions
Brief summary
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).
Interventions
DRUGPeg-Interferon Alpha-2A
Peg-IFN-Alpha-2A will be administered at 180 micrograms (mcg) once weekly via subcutaneous injection.
DRUGRibavirin
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.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response (SVR) | 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) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Undetectable HCV RNA 12 Weeks After the Last Dose of Peg-IFN-Alpha-2A | 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) | 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. |
| Percentage of Participants Without SVR Among Participants With Undetectable HCV RNA at the End of Treatment | 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) | 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). |
| Serum Human Immunodeficiency Virus (HIV) RNA Levels | 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 | 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). |
| Percentage of Participants With Undetectable HCV RNA | 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 | 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). |
| Change From Baseline in CD4/CD8 Ratio at Weeks 4, 12, 24, 48, 72, and 96 | 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 | 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). |
| Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | 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 | 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). |
| Change From Baseline in Cluster of Differentiation (CD) 4 (CD4) Cell Counts at Weeks 4, 12, 24, 48, 72, and 96 | 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 | 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). |
Countries
Brazil
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks Participants received Peg-IFN-Alpha-2A and ribavirin for 48 weeks. Peg-IFN-Alpha-2A was administered at 180 mcg once weekly via subcutaneous injection. Ribavirin was administered as either 1000 mg per day (2\*200 mg tablets in morning and 3\*200 mg tablets in evening) for participants weighing \<75 kilograms (kg) or as 1200 mg per day (3\*200 mg tablets in morning and 3\*200 mg tablets in evening) for participants weighing \>/=75 kg. | 80 |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks Participants received Peg-IFN-Alpha-2A and ribavirin for 72 weeks. Peg-IFN-Alpha-2A was administered at 180 mcg once weekly via subcutaneous injection. Ribavirin was administered as either 1000 mg per day (2\*200 mg tablets in morning and 3\*200 mg tablets in evening) for participants weighing \<75 kg or as 1200 mg per day (3\*200 mg tablets in morning and 3\*200 mg tablets in evening) for participants weighing \>/=75 kg. | 85 |
| Total | 165 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event/Intercurrent Illness | 7 | 5 |
| Overall Study | Did not Cooperate/Refused Treatment | 2 | 4 |
| Overall Study | Failure to Return | 2 | 4 |
| Overall Study | Insufficient Therapeutic Response | 2 | 7 |
| Overall Study | Lost to Follow-up | 4 | 1 |
| Overall Study | Other | 0 | 2 |
| Overall Study | Protocol Violation | 2 | 2 |
| Overall Study | Randomized But Not Treated | 8 | 4 |
| Overall Study | Withdrawal by Subject | 0 | 3 |
Baseline characteristics
| Characteristic | Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Total |
|---|---|---|---|
| Age, Continuous | 42.3 years STANDARD_DEVIATION 7.9 | 42.2 years STANDARD_DEVIATION 8.4 | 42.3 years STANDARD_DEVIATION 8.2 |
| Sex: Female, Male Female | 31 Participants | 26 Participants | 57 Participants |
| Sex: Female, Male Male | 49 Participants | 59 Participants | 108 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 79 / 82 | 81 / 86 |
| serious Total, serious adverse events | 7 / 82 | 12 / 86 |
Outcome results
Primary
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.
Time frame: 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)
Population: Intent-to-treat (ITT) analysis population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Percentage of Participants With Sustained Virologic Response (SVR) | 23.8 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Percentage of Participants With Sustained Virologic Response (SVR) | 36.5 percentage of participants |
p-value: 0.053695% CI: [-0.01, 26.6]Fisher Exact
Secondary
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).
Time frame: 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
Population: ITT analysis population. Here, number of participants analyzed = participants who were evaluable for this outcome and n = participants who were evaluable at specified time-point; for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Change From Baseline in CD4/CD8 Ratio at Weeks 4, 12, 24, 48, 72, and 96 | Change at Week 12 (n=68, 75) | 0.22 Ratio | Standard Deviation 0.31 |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Change From Baseline in CD4/CD8 Ratio at Weeks 4, 12, 24, 48, 72, and 96 | Change at Week 48 (n=61, 67) | 0.43 Ratio | Standard Deviation 0.47 |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Change From Baseline in CD4/CD8 Ratio at Weeks 4, 12, 24, 48, 72, and 96 | Change at Week 4 (n=69, 74) | 0.11 Ratio | Standard Deviation 0.42 |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Change From Baseline in CD4/CD8 Ratio at Weeks 4, 12, 24, 48, 72, and 96 | Change at Week 72 (n=58, 55) | 0.12 Ratio | Standard Deviation 0.41 |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Change From Baseline in CD4/CD8 Ratio at Weeks 4, 12, 24, 48, 72, and 96 | Change at Week 24 (n=69, 68) | 0.36 Ratio | Standard Deviation 0.51 |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Change From Baseline in CD4/CD8 Ratio at Weeks 4, 12, 24, 48, 72, and 96 | Change at Week 96 (n=0, 62) | NA Ratio | — |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Change From Baseline in CD4/CD8 Ratio at Weeks 4, 12, 24, 48, 72, and 96 | Baseline (n=78, 81) | 0.67 Ratio | Standard Deviation 0.39 |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Change From Baseline in CD4/CD8 Ratio at Weeks 4, 12, 24, 48, 72, and 96 | Change at Week 96 (n=0, 62) | 0.09 Ratio | Standard Deviation 0.35 |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Change From Baseline in CD4/CD8 Ratio at Weeks 4, 12, 24, 48, 72, and 96 | Baseline (n=78, 81) | 0.68 Ratio | Standard Deviation 0.44 |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Change From Baseline in CD4/CD8 Ratio at Weeks 4, 12, 24, 48, 72, and 96 | Change at Week 4 (n=69, 74) | 0.09 Ratio | Standard Deviation 0.21 |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Change From Baseline in CD4/CD8 Ratio at Weeks 4, 12, 24, 48, 72, and 96 | Change at Week 12 (n=68, 75) | 0.20 Ratio | Standard Deviation 0.27 |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Change From Baseline in CD4/CD8 Ratio at Weeks 4, 12, 24, 48, 72, and 96 | Change at Week 24 (n=69, 68) | 0.29 Ratio | Standard Deviation 0.3 |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Change From Baseline in CD4/CD8 Ratio at Weeks 4, 12, 24, 48, 72, and 96 | Change at Week 48 (n=61, 67) | 0.30 Ratio | Standard Deviation 0.43 |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Change From Baseline in CD4/CD8 Ratio at Weeks 4, 12, 24, 48, 72, and 96 | Change at Week 72 (n=58, 55) | 0.36 Ratio | Standard Deviation 0.43 |
Secondary
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).
Time frame: 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
Population: ITT analysis population. Here, number of participants analyzed = participants who were evaluable for this outcome and n = participants who were evaluable at specified time-point; for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Change From Baseline in Cluster of Differentiation (CD) 4 (CD4) Cell Counts at Weeks 4, 12, 24, 48, 72, and 96 | Change at Week 12 (n=68, 75) | -185.4 Cells per cubic millimeter (cells/mm^3) | Standard Deviation 192.7 |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Change From Baseline in Cluster of Differentiation (CD) 4 (CD4) Cell Counts at Weeks 4, 12, 24, 48, 72, and 96 | Change at Week 4 (n=69, 74) | -148.2 Cells per cubic millimeter (cells/mm^3) | Standard Deviation 197.5 |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Change From Baseline in Cluster of Differentiation (CD) 4 (CD4) Cell Counts at Weeks 4, 12, 24, 48, 72, and 96 | Change at Week 24 (n=69, 68) | -206.7 Cells per cubic millimeter (cells/mm^3) | Standard Deviation 217 |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Change From Baseline in Cluster of Differentiation (CD) 4 (CD4) Cell Counts at Weeks 4, 12, 24, 48, 72, and 96 | Change at Week 48 (n=61, 67) | -209.4 Cells per cubic millimeter (cells/mm^3) | Standard Deviation 242.4 |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Change From Baseline in Cluster of Differentiation (CD) 4 (CD4) Cell Counts at Weeks 4, 12, 24, 48, 72, and 96 | Change at Week 72 (n=58, 55) | 9.5 Cells per cubic millimeter (cells/mm^3) | Standard Deviation 188.9 |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Change From Baseline in Cluster of Differentiation (CD) 4 (CD4) Cell Counts at Weeks 4, 12, 24, 48, 72, and 96 | Change at Week 96 (n=0, 62) | NA Cells per cubic millimeter (cells/mm^3) | — |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Change From Baseline in Cluster of Differentiation (CD) 4 (CD4) Cell Counts at Weeks 4, 12, 24, 48, 72, and 96 | Baseline (n=78, 81) | 578.7 Cells per cubic millimeter (cells/mm^3) | Standard Deviation 277.1 |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Change From Baseline in Cluster of Differentiation (CD) 4 (CD4) Cell Counts at Weeks 4, 12, 24, 48, 72, and 96 | Change at Week 72 (n=58, 55) | -167.5 Cells per cubic millimeter (cells/mm^3) | Standard Deviation 235.8 |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Change From Baseline in Cluster of Differentiation (CD) 4 (CD4) Cell Counts at Weeks 4, 12, 24, 48, 72, and 96 | Baseline (n=78, 81) | 546.2 Cells per cubic millimeter (cells/mm^3) | Standard Deviation 278.8 |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Change From Baseline in Cluster of Differentiation (CD) 4 (CD4) Cell Counts at Weeks 4, 12, 24, 48, 72, and 96 | Change at Week 48 (n=61, 67) | -196.4 Cells per cubic millimeter (cells/mm^3) | Standard Deviation 226.4 |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Change From Baseline in Cluster of Differentiation (CD) 4 (CD4) Cell Counts at Weeks 4, 12, 24, 48, 72, and 96 | Change at Week 4 (n=69, 74) | -88.0 Cells per cubic millimeter (cells/mm^3) | Standard Deviation 154.9 |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Change From Baseline in Cluster of Differentiation (CD) 4 (CD4) Cell Counts at Weeks 4, 12, 24, 48, 72, and 96 | Change at Week 12 (n=68, 75) | -164.5 Cells per cubic millimeter (cells/mm^3) | Standard Deviation 193.9 |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Change From Baseline in Cluster of Differentiation (CD) 4 (CD4) Cell Counts at Weeks 4, 12, 24, 48, 72, and 96 | Change at Week 96 (n=0, 62) | -15.1 Cells per cubic millimeter (cells/mm^3) | Standard Deviation 212.2 |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Change From Baseline in Cluster of Differentiation (CD) 4 (CD4) Cell Counts at Weeks 4, 12, 24, 48, 72, and 96 | Change at Week 24 (n=69, 68) | -178.4 Cells per cubic millimeter (cells/mm^3) | Standard Deviation 207.5 |
Secondary
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).
Time frame: 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
Population: Safety analysis population: all randomized participants who receive \>/=1 dose of any study medication and had \>/=1 post-baseline safety assessment. Number of participants analyzed= overall participants who were evaluable for this outcome at any time-point and n = participants who were evaluable at specified time-point; for each arm, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 48, >1-2 ULN (n=65, 71) | 24.6 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 12, >10 ULN (n=76, 77) | 0.0 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 48, >2-5 ULN (n=65, 71) | 7.7 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 4, >5-10 ULN (n=70, 78) | 0.0 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 48, >5-10 ULN (n=65, 71) | 0.0 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 24, NL (n=74, 74) | 70.3 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 48, >10 ULN (n=65, 71) | 0.0 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 12, >1-2 ULN (n=76, 77) | 27.6 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 72, NL (n=59, 61) | 52.5 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 24, >1-2 ULN (n=74, 74) | 27.0 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 72, >1-2 ULN (n=59, 61) | 27.1 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 4, >2-5 ULN (n=70, 78) | 10.0 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 72, >2-5 ULN (n=59, 61) | 20.3 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 24, >2-5 ULN (n=74, 74) | 2.7 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 72, >5-10 ULN (n=59, 61) | 0.0 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 12, >2-5 ULN (n=76, 77) | 10.5 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 72, >10 ULN (n=59, 61) | 0.0 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 24, >5-10 ULN (n=74, 74) | 0.0 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 96, NL (n=0, 62) | NA percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 4, >10 ULN (n=70, 78) | 0.0 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 96, >1-2 ULN (n=0, 62) | NA percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 24, >10 ULN (n=74, 74) | 0.0 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 96, >2-5 ULN (n=0, 62) | NA percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 12, >5-10 ULN (n=76, 77) | 0.0 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 96, >5-10 ULN (n=0, 62) | NA percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 48, NL (n=65, 71) | 67.7 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 96, >10 ULN (n=0, 62) | NA percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 4, >1-2 ULN (n=70, 78) | 40.0 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 4, NL (n=70, 78) | 50.0 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 12, NL (n=76, 77) | 61.8 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 4, NL (n=70, 78) | 52.6 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 4, >1-2 ULN (n=70, 78) | 38.5 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 4, >2-5 ULN (n=70, 78) | 9.0 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 4, >5-10 ULN (n=70, 78) | 0.0 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 4, >10 ULN (n=70, 78) | 0.0 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 12, NL (n=76, 77) | 62.3 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 12, >1-2 ULN (n=76, 77) | 29.9 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 12, >2-5 ULN (n=76, 77) | 5.2 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 12, >5-10 ULN (n=76, 77) | 1.3 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 12, >10 ULN (n=76, 77) | 1.3 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 24, NL (n=74, 74) | 63.5 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 24, >1-2 ULN (n=74, 74) | 28.4 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 24, >2-5 ULN (n=74, 74) | 6.8 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 24, >5-10 ULN (n=74, 74) | 0.0 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 24, >10 ULN (n=74, 74) | 1.4 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 48, NL (n=65, 71) | 69.0 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 48, >1-2 ULN (n=65, 71) | 26.8 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 48, >2-5 ULN (n=65, 71) | 2.8 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 48, >5-10 ULN (n=65, 71) | 1.4 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 48, >10 ULN (n=65, 71) | 0.0 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 72, NL (n=59, 61) | 68.9 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 72, >1-2 ULN (n=59, 61) | 27.9 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 72, >2-5 ULN (n=59, 61) | 3.3 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 72, >5-10 ULN (n=59, 61) | 0.0 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 72, >10 ULN (n=59, 61) | 0.0 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 96, NL (n=0, 62) | 50.0 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 96, >1-2 ULN (n=0, 62) | 35.5 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 96, >2-5 ULN (n=0, 62) | 12.9 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 96, >5-10 ULN (n=0, 62) | 1.6 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Percentage of Participants With Alanine Aminotransferase (ALT) Level Categories | Week 96, >10 ULN (n=0, 62) | 0.0 percentage of participants |
Secondary
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).
Time frame: 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)
Population: ITT analysis population. Here, number of participants analyzed signifies participants with undetectable HCV RNA at the end of treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Percentage of Participants Without SVR Among Participants With Undetectable HCV RNA at the End of Treatment | 52.6 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Percentage of Participants Without SVR Among Participants With Undetectable HCV RNA at the End of Treatment | 24.3 percentage of participants |
p-value: 0.0175Fisher Exact
Secondary
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).
Time frame: 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
Population: ITT analysis population. Here, number of participants analyzed = participants who were evaluable for this outcome and n = participants who were evaluable for this outcome at specified time-point; for each arm, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Percentage of Participants With Undetectable HCV RNA | Week 12 (n=73, 81) | 23.3 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Percentage of Participants With Undetectable HCV RNA | Week 48 (n=68, 71) | 55.9 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Percentage of Participants With Undetectable HCV RNA | Week 24 (n=73, 78) | 52.1 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Percentage of Participants With Undetectable HCV RNA | Week 72 (n=0, 65) | NA percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Percentage of Participants With Undetectable HCV RNA | Week 4 (n=73, 83) | 2.7 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Percentage of Participants With Undetectable HCV RNA | Week 72 (n=0, 65) | 56.9 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Percentage of Participants With Undetectable HCV RNA | Week 4 (n=73, 83) | 12.0 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Percentage of Participants With Undetectable HCV RNA | Week 12 (n=73, 81) | 28.4 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Percentage of Participants With Undetectable HCV RNA | Week 24 (n=73, 78) | 53.8 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Percentage of Participants With Undetectable HCV RNA | Week 48 (n=68, 71) | 64.8 percentage of participants |
Secondary
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.
Time frame: 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)
Population: ITT analysis population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Percentage of Participants With Undetectable HCV RNA 12 Weeks After the Last Dose of Peg-IFN-Alpha-2A | 23.8 percentage of participants |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Percentage of Participants With Undetectable HCV RNA 12 Weeks After the Last Dose of Peg-IFN-Alpha-2A | 36.5 percentage of participants |
Secondary
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).
Time frame: 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
Population: ITT analysis population. Here, number of participants analyzed = participants with detectable HIV RNA levels and n = participants with detectable HIV RNA levels at specified time-point; for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Serum Human Immunodeficiency Virus (HIV) RNA Levels | Baseline (n=12, 23) | 4.23 Log10 copies per milliliter | Standard Deviation 0.82 |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Serum Human Immunodeficiency Virus (HIV) RNA Levels | Week 4 (n=6, 16) | 3.94 Log10 copies per milliliter | Standard Deviation 0.38 |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Serum Human Immunodeficiency Virus (HIV) RNA Levels | Week 24 (n=9, 20) | 3.96 Log10 copies per milliliter | Standard Deviation 0.36 |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Serum Human Immunodeficiency Virus (HIV) RNA Levels | Week 48 (n=11, 17) | 4.02 Log10 copies per milliliter | Standard Deviation 0.65 |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Serum Human Immunodeficiency Virus (HIV) RNA Levels | Week 72 (n=10, 9) | 4.08 Log10 copies per milliliter | Standard Deviation 0.78 |
| Peg-IFN-Alpha-2A+Ribavirin - 48 Weeks | Serum Human Immunodeficiency Virus (HIV) RNA Levels | Week 96 (n=0, 13) | NA Log10 copies per milliliter | — |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Serum Human Immunodeficiency Virus (HIV) RNA Levels | Week 72 (n=10, 9) | 4.51 Log10 copies per milliliter | Standard Deviation 0.85 |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Serum Human Immunodeficiency Virus (HIV) RNA Levels | Baseline (n=12, 23) | 4.64 Log10 copies per milliliter | Standard Deviation 0.74 |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Serum Human Immunodeficiency Virus (HIV) RNA Levels | Week 48 (n=11, 17) | 4.41 Log10 copies per milliliter | Standard Deviation 0.75 |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Serum Human Immunodeficiency Virus (HIV) RNA Levels | Week 4 (n=6, 16) | 3.98 Log10 copies per milliliter | Standard Deviation 0.69 |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Serum Human Immunodeficiency Virus (HIV) RNA Levels | Week 96 (n=0, 13) | 4.22 Log10 copies per milliliter | Standard Deviation 0.85 |
| Peg-IFN-Alpha-2A+Ribavirin - 72 Weeks | Serum Human Immunodeficiency Virus (HIV) RNA Levels | Week 24 (n=9, 20) | 4.21 Log10 copies per milliliter | Standard Deviation 0.72 |