Hepatitis C, Chronic
Conditions
Brief summary
This study will compare the efficacy and safety of treatment with pegylated-interferon alfa-2a plus ribavirin in participants with non-genotype 2/3 CHC who, after 12 weeks of study treatment, have undetectable hepatitis C virus (HCV)-ribonucleic acid (RNA) or a greater than or equal to (\>=) 2 log10 drop in HCV-RNA. Participants will be randomized to receive pegylated-interferon alfa-2a 180 micrograms subcutaneously weekly plus ribavirin (1000-1400 milligram \[mg\]) orally daily for the specified duration, followed by 24 weeks of treatment-free follow-up. Participants with detectable HCV-RNA and less than (\<) 2 log10 drop in HCV-RNA at week 12 will discontinue therapy.
Interventions
Participants will receive pegylated-interferon alfa-2a 180 mcg subcutaneously once in a week for the specified duration.
DRUGRibavirin
Participants will receive ribavirin 1000 to 1400 mg orally daily for the specified duration.
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
* evidence of CHC; * evidence of hepatitis C non-genotype 2 or 3; * compensated liver disease.
Exclusion criteria
* infection with HCV genotype 2 or 3; * history of having received systemic antiviral therapy with activity against CHC \<=3 months prior to start of study; * hepatitis A, hepatitis B or human immunodeficiency virus (HIV) infection; * history or evidence of a medical condition associated with chronic liver disease other than CHC.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virological Response (SVR) (Groups A and B) | At 24-week untreated follow-up visit (up to 72 weeks for Group A, up to 96 weeks for Group B) | SVR was defined as success if the participant had HCV RNA levels \<15 IU/mL as measured by COBAS AmpliPrep/COBAS TaqMan® HCV test at the 24-week untreated follow-up visit (HCV-RNA levels obtained at least 18 weeks after last dose of either pegylated-Interferon alfa-2a or ribavirin were considered if the 24-week untreated follow-up visit data were missing). Percentage of participants with SVR for Groups A and B was reported in this analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With SVR (Groups C, D, E, and F) | At 24-week untreated follow-up visit (up to 60, 72, 48, and 72 weeks for Groups C, D, E, and F, respectively) | SVR was defined as success if the participant had HCV RNA levels \<15 IU/mL as measured by COBAS AmpliPrep/COBAS TaqMan® HCV test at the 24-week untreated follow-up visit (HCV-RNA levels obtained at least 18 weeks after last dose of either pegylated-Interferon alfa-2a or ribavirin were considered if the 24-week untreated follow-up visit data were missing). Percentage of participants with SVR for Groups C, D, E, and F was reported in this analysis. |
| Percentage of Participants With Virological Responses (Groups A, B, C, D, E, and F) | Week 12 (Groups C, D, E, and F), and end of treatment (Weeks 48, 72, 36, 48, 24, and 48 for Groups A, B, C, D, E, and F, respectively) | End of treatment response (ETR) was defined as Success if the HCV-RNA levels were \<15 IU/mL at the end of treatment. Early virological response (EVR) was defined as \>=2 log10 decrease in serum HCV RNA or undetectable serum HCV RNA (\<15 IU/mL) at Week 12. Complete EVR was defined as Success, if the HCV-RNA levels were \<15 IU/mL at Week 12. Partial EVR was defined as Success, if there was a \>=2 log10 drop in HCV-RNA at Week 12 compared to baseline but with a level that was still \>=15 IU/mL at that time point. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pegylated-interferon Alfa-2a + Ribavirin (Group A) Participants with hepatitis C virus (HCV) ribonucleic acid (RNA) levels greater than (\>) 15 international units per milliliter (IU/mL) at Week 4, HCV RNA greater than or equal to (\>=) 15 IU/mL at Week 8, and either HCV RNA less than (\<) 15 IU/mL or \>=2 times logarithmic (2 log10) drop at Week 12, received pegylated-interferon alfa-2a (Pegasys) 180 micrograms (mcg) subcutaneously once in a week for 48 weeks, and ribavirin (Copegus) 1000 to 1400 milligrams (mg) orally daily for 48 weeks. | 41 |
| Pegylated-interferon Alfa-2a + Ribavirin (Group B) Participants with HCV RNA levels \>15 IU/mL at Week 4, HCV RNA \>=15 IU/mL at Week 8, and either HCV RNA \<15 IU/mL or \>=2 log10 drop at Week 12, received pegylated-interferon alfa-2a 180 mcg subcutaneously once in a week for 72 weeks, and ribavirin 1000 to 1400 mg orally daily for 72 weeks. | 43 |
| Pegylated-interferon Alfa-2a + Ribavirin (Group C) Participants with HCV-RNA levels \>15 IU/mL at Week 4, and HCV-RNA \<15 IU/mL at Week 8, received pegylated-interferon alfa-2a 180 mcg subcutaneously once in a week for 36 weeks, and ribavirin 1000 to 1400 mg orally daily for 36 weeks. | 30 |
| Pegylated-interferon Alfa-2a + Ribavirin (Group D) Participants with HCV-RNA levels \>15 IU/mL at Week 4, and HCV-RNA \<15 IU/mL at Week 8, received pegylated-interferon alfa-2a 180 mcg subcutaneously once in a week for 48 weeks, and ribavirin 1000 to 1400 mg orally daily for 48 weeks. | 31 |
| Pegylated-interferon Alfa-2a + Ribavirin (Group E) Participants with HCV-RNA levels \<15 IU/mL at Week 4, received pegylated-interferon alfa-2a 180 mcg subcutaneously once in a week for 24 weeks, and ribavirin 1000 to 1400 mg orally daily for 24 weeks. | 25 |
| Pegylated-interferon Alfa-2a + Ribavirin (Group F) Participants with HCV-RNA levels \<15 IU/mL at Week 4, received pegylated-interferon alfa-2a 180 mcg subcutaneously once in a week for 48 weeks, and ribavirin 1000 to 1400 mg orally daily for 48 weeks. | 26 |
| Pegylated-interferon Alfa-2a + Ribavirin (Group NR) Participants who did not have any change in HCV-RNA levels at Weeks 4, 8, and 12 were not randomized (NR) to any of the other groups. Participants received pegylated-interferon alfa-2a 180 mcg subcutaneously once in a week for 48 weeks, and ribavirin 1000 to 1400 mg orally daily for 48 weeks. | 40 |
| Total | 236 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 0 | 2 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 1 | 2 | 0 | 2 | 1 | 1 | 3 |
| Overall Study | Other | 3 | 9 | 0 | 4 | 0 | 4 | 32 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 0 | 3 |
| Overall Study | Withdrawal by Subject | 1 | 6 | 0 | 0 | 1 | 3 | 2 |
Baseline characteristics
| Characteristic | Pegylated-interferon Alfa-2a + Ribavirin (Group A) | Pegylated-interferon Alfa-2a + Ribavirin (Group B) | Pegylated-interferon Alfa-2a + Ribavirin (Group C) | Pegylated-interferon Alfa-2a + Ribavirin (Group D) | Pegylated-interferon Alfa-2a + Ribavirin (Group E) | Pegylated-interferon Alfa-2a + Ribavirin (Group F) | Pegylated-interferon Alfa-2a + Ribavirin (Group NR) | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 50.9 years STANDARD_DEVIATION 8.55 | 51.0 years STANDARD_DEVIATION 7.39 | 48.7 years STANDARD_DEVIATION 11.54 | 47.8 years STANDARD_DEVIATION 9.16 | 47.0 years STANDARD_DEVIATION 10.38 | 47.0 years STANDARD_DEVIATION 9.76 | 51.7 years STANDARD_DEVIATION 7.52 | 49.5 years STANDARD_DEVIATION 9.13 |
| Gender Female | 16 Participants | 19 Participants | 10 Participants | 12 Participants | 6 Participants | 9 Participants | 13 Participants | 85 Participants |
| Gender Male | 25 Participants | 24 Participants | 20 Participants | 19 Participants | 19 Participants | 17 Participants | 27 Participants | 151 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 39 / 41 | 43 / 43 | 30 / 30 | 31 / 31 | 25 / 25 | 25 / 26 | 35 / 40 |
| serious Total, serious adverse events | 4 / 41 | 6 / 43 | 5 / 30 | 4 / 31 | 0 / 25 | 4 / 26 | 3 / 40 |
Outcome results
Primary
Percentage of Participants With Sustained Virological Response (SVR) (Groups A and B)
SVR was defined as success if the participant had HCV RNA levels \<15 IU/mL as measured by COBAS AmpliPrep/COBAS TaqMan® HCV test at the 24-week untreated follow-up visit (HCV-RNA levels obtained at least 18 weeks after last dose of either pegylated-Interferon alfa-2a or ribavirin were considered if the 24-week untreated follow-up visit data were missing). Percentage of participants with SVR for Groups A and B was reported in this analysis.
Time frame: At 24-week untreated follow-up visit (up to 72 weeks for Group A, up to 96 weeks for Group B)
Population: Intent-to-treat (ITT) population included randomized participants who received at least one dose of study medication and who had a baseline HCV-RNA which was at least 15 IU/mL. Here, Number of Participants Analyzed = the participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegylated-interferon Alfa-2a + Ribavirin (Group A) | Percentage of Participants With Sustained Virological Response (SVR) (Groups A and B) | 48.8 percentage of participants |
| Pegylated-interferon Alfa-2a + Ribavirin (Group B) | Percentage of Participants With Sustained Virological Response (SVR) (Groups A and B) | 39.5 percentage of participants |
Comparison: SVR: Group A versus Group Bp-value: 0.51Fisher Exact
Secondary
Percentage of Participants With SVR (Groups C, D, E, and F)
SVR was defined as success if the participant had HCV RNA levels \<15 IU/mL as measured by COBAS AmpliPrep/COBAS TaqMan® HCV test at the 24-week untreated follow-up visit (HCV-RNA levels obtained at least 18 weeks after last dose of either pegylated-Interferon alfa-2a or ribavirin were considered if the 24-week untreated follow-up visit data were missing). Percentage of participants with SVR for Groups C, D, E, and F was reported in this analysis.
Time frame: At 24-week untreated follow-up visit (up to 60, 72, 48, and 72 weeks for Groups C, D, E, and F, respectively)
Population: ITT. Here, Number of Participants Analyzed = the participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegylated-interferon Alfa-2a + Ribavirin (Group A) | Percentage of Participants With SVR (Groups C, D, E, and F) | 73.3 percentage of participants |
| Pegylated-interferon Alfa-2a + Ribavirin (Group B) | Percentage of Participants With SVR (Groups C, D, E, and F) | 74.2 percentage of participants |
| Pegylated-interferon Alfa-2a + Ribavirin (Group E) | Percentage of Participants With SVR (Groups C, D, E, and F) | 84.0 percentage of participants |
| Pegylated-interferon Alfa-2a + Ribavirin (Group F) | Percentage of Participants With SVR (Groups C, D, E, and F) | 84.0 percentage of participants |
Comparison: SVR: Group C versus Group Dp-value: 1Fisher Exact
Comparison: SVR: Group E versus Group Fp-value: 1Fisher Exact
Secondary
Percentage of Participants With Virological Responses (Groups A, B, C, D, E, and F)
End of treatment response (ETR) was defined as Success if the HCV-RNA levels were \<15 IU/mL at the end of treatment. Early virological response (EVR) was defined as \>=2 log10 decrease in serum HCV RNA or undetectable serum HCV RNA (\<15 IU/mL) at Week 12. Complete EVR was defined as Success, if the HCV-RNA levels were \<15 IU/mL at Week 12. Partial EVR was defined as Success, if there was a \>=2 log10 drop in HCV-RNA at Week 12 compared to baseline but with a level that was still \>=15 IU/mL at that time point.
Time frame: Week 12 (Groups C, D, E, and F), and end of treatment (Weeks 48, 72, 36, 48, 24, and 48 for Groups A, B, C, D, E, and F, respectively)
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pegylated-interferon Alfa-2a + Ribavirin (Group A) | Percentage of Participants With Virological Responses (Groups A, B, C, D, E, and F) | Complete EVR | 0 percentage of participants |
| Pegylated-interferon Alfa-2a + Ribavirin (Group A) | Percentage of Participants With Virological Responses (Groups A, B, C, D, E, and F) | ETR | 80.5 percentage of participants |
| Pegylated-interferon Alfa-2a + Ribavirin (Group A) | Percentage of Participants With Virological Responses (Groups A, B, C, D, E, and F) | Partial EVR | 0 percentage of participants |
| Pegylated-interferon Alfa-2a + Ribavirin (Group B) | Percentage of Participants With Virological Responses (Groups A, B, C, D, E, and F) | Complete EVR | 0 percentage of participants |
| Pegylated-interferon Alfa-2a + Ribavirin (Group B) | Percentage of Participants With Virological Responses (Groups A, B, C, D, E, and F) | ETR | 76.7 percentage of participants |
| Pegylated-interferon Alfa-2a + Ribavirin (Group B) | Percentage of Participants With Virological Responses (Groups A, B, C, D, E, and F) | Partial EVR | 0 percentage of participants |
| Pegylated-interferon Alfa-2a + Ribavirin (Group E) | Percentage of Participants With Virological Responses (Groups A, B, C, D, E, and F) | Complete EVR | 93.3 percentage of participants |
| Pegylated-interferon Alfa-2a + Ribavirin (Group E) | Percentage of Participants With Virological Responses (Groups A, B, C, D, E, and F) | ETR | 96.7 percentage of participants |
| Pegylated-interferon Alfa-2a + Ribavirin (Group E) | Percentage of Participants With Virological Responses (Groups A, B, C, D, E, and F) | Partial EVR | 0 percentage of participants |
| Pegylated-interferon Alfa-2a + Ribavirin (Group F) | Percentage of Participants With Virological Responses (Groups A, B, C, D, E, and F) | Complete EVR | 96.8 percentage of participants |
| Pegylated-interferon Alfa-2a + Ribavirin (Group F) | Percentage of Participants With Virological Responses (Groups A, B, C, D, E, and F) | ETR | 90.3 percentage of participants |
| Pegylated-interferon Alfa-2a + Ribavirin (Group F) | Percentage of Participants With Virological Responses (Groups A, B, C, D, E, and F) | Partial EVR | 3.2 percentage of participants |
| Pegylated-interferon Alfa-2a + Ribavirin (Group E) | Percentage of Participants With Virological Responses (Groups A, B, C, D, E, and F) | Complete EVR | 88.0 percentage of participants |
| Pegylated-interferon Alfa-2a + Ribavirin (Group E) | Percentage of Participants With Virological Responses (Groups A, B, C, D, E, and F) | ETR | 92.0 percentage of participants |
| Pegylated-interferon Alfa-2a + Ribavirin (Group E) | Percentage of Participants With Virological Responses (Groups A, B, C, D, E, and F) | Partial EVR | 0 percentage of participants |
| Pegylated-interferon Alfa-2a + Ribavirin (Group F) | Percentage of Participants With Virological Responses (Groups A, B, C, D, E, and F) | ETR | 100.0 percentage of participants |
| Pegylated-interferon Alfa-2a + Ribavirin (Group F) | Percentage of Participants With Virological Responses (Groups A, B, C, D, E, and F) | Partial EVR | 0 percentage of participants |
| Pegylated-interferon Alfa-2a + Ribavirin (Group F) | Percentage of Participants With Virological Responses (Groups A, B, C, D, E, and F) | Complete EVR | 92.0 percentage of participants |
Comparison: ETR: Group A versus Group Bp-value: 0.792Fisher Exact
Comparison: ETR: Group C versus Group Dp-value: 0.612Fisher Exact
Comparison: ETR: Group E versus Group Fp-value: 0.49Fisher Exact
Comparison: Complete EVR: Group C versus Group Dp-value: 0.363Fisher Exact
Comparison: Complete EVR: Group E versus Group Fp-value: 1Fisher Exact