Hepatitis C, Chronic
Conditions
Brief summary
The purpose of this study is to evaluate the safety, tolerability, and efficacy of vaniprevir given in combination with pegylated interferon alfa-2b (peg-IFN) and ribavirin (RBV) versus treatment with peg-IFN and RBV alone in Japanese treatment-naïve participants with chronic hepatitis C (CHC) genotype (GT)1. The primary efficacy hypothesis is that the percentage of participants achieving sustained virologic response 24 weeks after completion of all study therapy (SVR24) in at least one of the vaniprevir arms is superior to the percentage of participants achieving SVR24 in the control arm.
Interventions
DRUGvaniprevir
Capsules containing 150 mg vaniprevir, orally, two in the morning and two in the evening for 12 or 24 weeks
DRUGPlacebo to vaniprevir
Placebo to vaniprevir, capsules, orally, twice daily for 12 weeks or 24 weeks
BIOLOGICALPeg-IFN
Peg-IFN 1.5 μg/kg once per week, subcutaneously (SC) for 24 or 48 weeks
DRUGribavirin
Capsules containing 200 mg RBV orally, 3 to 5 capsules, dosage based on the participant's weight (600 mg/day to 1000 mg/day), for 24 or 48 weeks
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Japanese participant diagnosed with compensated CHC GT 1 * Absence of ascites, bleeding esophageal varices, hepatic encephalopathy, or other signs or symptoms of advanced liver disease. * IFN treatment naive * No evidence of cirrhosis
Exclusion criteria
* Co-infection with human immunodeficiency virus (HIV) * Positive hepatitis B surface antigen or other evidence of active hepatitis B infection * Any other condition that is contraindicated or for which caution is required for treatment with peg-IFN or RBV * Any condition or pre-study laboratory abnormality, or history of any illness, that, in the opinion of the investigator, might confound the results of the study or pose additional risk in administering the study drugs, peg-IFN and RBV, to the participant.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Completion of All Study Therapy (SVR24) | 24 weeks after 24 or 48 weeks of study therapy (up to 72 weeks) | SVR24 was defined as having an undetectable HCV RNA level 24 weeks after completion of all study therapy. |
| Percentage of Participants With One or More Tier 1 Adverse Events (AEs) During the Study | From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 72 weeks) | An adverse experience was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the product, was also an adverse experience. For this study, safety parameters or AEs of special interest that were identified a priori constituted Tier 1 safety endpoints that were subject to inferential testing for statistical significance. Tier 1 AEs on this study included serious rash, anemia (anemia plus haemoglobin decreased), neutropenia (neutropenia plus neutrophil count decreased), bilirubin increased and gastrointestinal adverse (GI) experiences (vomiting, nausea, and diarrhea). |
| Percentage of Participants Who Discontinued Study Drug Due to an AE | From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 72 weeks) | An adverse experience was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the product, was also an adverse experience. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Undetectable HCV RNA at the End of Treatment (EOT) | At Week 24 or 48 | Participants were assessed for undetectable HCV RNA levels at the end of all study therapy. |
| Percentage of Participants Achieving SVR12 | 12 weeks after 24 or 48 weeks of study therapy (up to 60 weeks) | SVR12 was defined as having an undetectable HCV RNA level 12 weeks after completion of all study therapy. |
| Least Squares (LS) Mean Change From Baseline in HCV RNA (Log 10) | Baseline, Week 2, Week 4, Week 8, Week 12, Week 24 | HCV RNA levels were assessed at baseline (BL) and during treatment weeks 2, 4, 8, 12, and 24 using the Roche TaqMan HCV assay, and transformed to Log 10 values. HCV RNA values below the limit of reliable quantification (LoQ) or the limit of detection (LoD) at any time point were handled as follows (imputations done for computational purposes): values below the LoQ but above the LoD were imputed with the LoQ minus 0.1; values below the LoD were imputed with the value of 0 Log IU/mL. HCV RNA levels below the LoD were considered undetectable. |
| Percentage of Participants Achieving Rapid Virologic Response (RVR) | At Week 4 | RVR was defined as having an undetectable HCV RNA level at Week 4. |
| Percentage of Participants Achieving Complete Early Virologic Response (cEVR) | At Week 12 | cEVR was defined as having an undetectable HCV RNA level at Week 12. |
Participant flow
Recruitment details
Japanese patients 20-70 years old (inclusive) who had chronic, compensated, genotype 1 Hepatitis C (HCV) infection, and HCV ribonucleic acid (RNA) levels ≥ 5.0 log IU/mL peripheral blood at screening were recruited from 55 sites in Japan.
Pre-assignment details
Of 294 randomized participants, 293 received at least 1 dose of study treatment and comprised the All Participants As Treated Population (APaT) as well as the Full Analysis Set (FAS). One treated participant was excluded from the FAS and APaT due to a protocol violation.
Participants by arm
| Arm | Count |
|---|---|
| Vaniprevir 12 Week Arm Participants on this arm receive 12 weeks of vaniprevir (300 mg twice daily) and then 12 weeks of placebo to vaniprevir along with 24 weeks of treatment with peg-IFN and RBV. | 98 |
| Vaniprevir 24 Week Arm Participants on this arm receive 24 weeks of vaniprevir (300 mg twice daily) along with 24 weeks of treatment with peg-IFN and RBV. | 98 |
| Control Arm Participants on this arm receive 24 weeks of treatment with placebo to vaniprevir along with 48 weeks of treatment with peg-IFN and RBV. | 98 |
| Total | 294 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 | 1 |
| Overall Study | Detectable HCV RNA | 0 | 0 | 22 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
| Overall Study | Physician Decision | 4 | 1 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 4 | 3 |
Baseline characteristics
| Characteristic | Vaniprevir 12 Week Arm | Vaniprevir 24 Week Arm | Control Arm | Total |
|---|---|---|---|---|
| Age, Continuous | 53.2 years STANDARD_DEVIATION 12 | 55.5 years STANDARD_DEVIATION 9.7 | 54.8 years STANDARD_DEVIATION 9.9 | 54.5 years STANDARD_DEVIATION 10.6 |
| Sex: Female, Male Female | 56 Participants | 49 Participants | 52 Participants | 157 Participants |
| Sex: Female, Male Male | 42 Participants | 49 Participants | 46 Participants | 137 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 98 / 98 | 97 / 97 | 98 / 98 |
| serious Total, serious adverse events | 5 / 98 | 6 / 97 | 9 / 98 |
Outcome results
Primary
Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Completion of All Study Therapy (SVR24)
SVR24 was defined as having an undetectable HCV RNA level 24 weeks after completion of all study therapy.
Time frame: 24 weeks after 24 or 48 weeks of study therapy (up to 72 weeks)
Population: Full Analysis Set (FAS) population; all randomized participants who received at least one dose of study treatment. One treated participant was excluded from the FAS due to a protocol violation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vaniprevir 12 Week Arm | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Completion of All Study Therapy (SVR24) | 83.7 percentage of participants |
| Vaniprevir 24 Week Arm | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Completion of All Study Therapy (SVR24) | 84.5 percentage of participants |
| Control Arm | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Completion of All Study Therapy (SVR24) | 55.1 percentage of participants |
Comparison: To compare the percentage of participants achieving SVR24 between the vaniprevir and control arms, 95% confidence intervals and corresponding p-values for the between-treatment difference (vaniprevir - control) were computed using Miettinen and Nurminen method stratified by Interleukin 28B (IL28B) and age utilizing Cochran-Mantel-Haenszel weights.p-value: <0.00195% CI: [17.2, 40.5]Miettinen and Nurminen method
Comparison: To compare the percentage of participants achieving SVR24 between the vaniprevir and control arms, 95% confidence intervals and corresponding p-values for the between-treatment difference (vaniprevir - control) were computed using Miettinen and Nurminen method stratified by IL28B and age utilizing Cochran-Mantel-Haenszel weights.p-value: <0.00195% CI: [17.4, 40]Miettinen and Nurminen method
Primary
Percentage of Participants Who Discontinued Study Drug Due to an AE
An adverse experience was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the product, was also an adverse experience.
Time frame: From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 72 weeks)
Population: All Participants Treated (APaT) Population; all participants receiving at least one dose of study treatment. One treated participant was excluded from the APaT due to a protocol violation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vaniprevir 12 Week Arm | Percentage of Participants Who Discontinued Study Drug Due to an AE | 7.1 percentage of participants |
| Vaniprevir 24 Week Arm | Percentage of Participants Who Discontinued Study Drug Due to an AE | 3.1 percentage of participants |
| Control Arm | Percentage of Participants Who Discontinued Study Drug Due to an AE | 11.2 percentage of participants |
Primary
Percentage of Participants With One or More Tier 1 Adverse Events (AEs) During the Study
An adverse experience was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the product, was also an adverse experience. For this study, safety parameters or AEs of special interest that were identified a priori constituted Tier 1 safety endpoints that were subject to inferential testing for statistical significance. Tier 1 AEs on this study included serious rash, anemia (anemia plus haemoglobin decreased), neutropenia (neutropenia plus neutrophil count decreased), bilirubin increased and gastrointestinal adverse (GI) experiences (vomiting, nausea, and diarrhea).
Time frame: From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 72 weeks)
Population: All Participants Treated (APaT) Population; all participants receiving at least one dose of study treatment. One treated participant was excluded from the APaT due to a protocol violation.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vaniprevir 12 Week Arm | Percentage of Participants With One or More Tier 1 Adverse Events (AEs) During the Study | With ≥1 Tier 1 AEs | 89.8 percentage of participants |
| Vaniprevir 12 Week Arm | Percentage of Participants With One or More Tier 1 Adverse Events (AEs) During the Study | anaemia | 60.2 percentage of participants |
| Vaniprevir 12 Week Arm | Percentage of Participants With One or More Tier 1 Adverse Events (AEs) During the Study | bilirubin increased | 7.1 percentage of participants |
| Vaniprevir 12 Week Arm | Percentage of Participants With One or More Tier 1 Adverse Events (AEs) During the Study | GI AEs | 62.2 percentage of participants |
| Vaniprevir 12 Week Arm | Percentage of Participants With One or More Tier 1 Adverse Events (AEs) During the Study | neutropenia | 59.2 percentage of participants |
| Vaniprevir 24 Week Arm | Percentage of Participants With One or More Tier 1 Adverse Events (AEs) During the Study | neutropenia | 51.5 percentage of participants |
| Vaniprevir 24 Week Arm | Percentage of Participants With One or More Tier 1 Adverse Events (AEs) During the Study | With ≥1 Tier 1 AEs | 83.5 percentage of participants |
| Vaniprevir 24 Week Arm | Percentage of Participants With One or More Tier 1 Adverse Events (AEs) During the Study | bilirubin increased | 12.4 percentage of participants |
| Vaniprevir 24 Week Arm | Percentage of Participants With One or More Tier 1 Adverse Events (AEs) During the Study | GI AEs | 52.6 percentage of participants |
| Vaniprevir 24 Week Arm | Percentage of Participants With One or More Tier 1 Adverse Events (AEs) During the Study | anaemia | 51.5 percentage of participants |
| Control Arm | Percentage of Participants With One or More Tier 1 Adverse Events (AEs) During the Study | With ≥1 Tier 1 AEs | 85.7 percentage of participants |
| Control Arm | Percentage of Participants With One or More Tier 1 Adverse Events (AEs) During the Study | neutropenia | 51.0 percentage of participants |
| Control Arm | Percentage of Participants With One or More Tier 1 Adverse Events (AEs) During the Study | bilirubin increased | 701 percentage of participants |
| Control Arm | Percentage of Participants With One or More Tier 1 Adverse Events (AEs) During the Study | anaemia | 64.3 percentage of participants |
| Control Arm | Percentage of Participants With One or More Tier 1 Adverse Events (AEs) During the Study | GI AEs | 46.9 percentage of participants |
Comparison: Difference in percentage of participants with ≥1 Tier 1 AEs between vaniprevir and control.p-value: 0.38595% CI: [-5.4, 13.7]Miettinen and Nurminen method
Comparison: Difference in percentage of participants with ≥1 Tier 1 AEs between vaniprevir and control.p-value: 0.6795% CI: [-12.6, 8.1]Miettinen and Nurminen method
Comparison: Difference in percentage of participants with anemia Tier 1 AEs between vaniprevir and control.p-value: 0.55795% CI: [-17.5, 9.5]Miettinen and Nurminen method
Comparison: Difference in percentage of participants with anemia Tier 1 AEs between vaniprevir and control.p-value: 0.07295% CI: [-26.2, 1.2]Miettinen and Nurminen method
Comparison: Difference in percentage of participants with bilirubin increased Tier 1 AEs between vaniprevir and control.p-value: >0.99995% CI: [-7.9, 7.9]Miettinen and Nurminen method
Comparison: Difference in percentage of participants with bilirubin increased Tier 1 AEs between vaniprevir and control.p-value: 0.2295% CI: [-3.3, 14.2]Miettinen and Nurminen method
Comparison: Difference in percentage of participants with GI Tier 1 AEs between vaniprevir and control.p-value: 0.03295% CI: [1.3, 28.7]Miettinen and Nurminen method
Comparison: Difference in percentage of participants with GI Tier 1 AEs between vaniprevir and control.p-value: 0.43295% CI: [-8.4, 19.4]Miettinen and Nurminen method
Comparison: Difference in percentage of participants with neutropenia Tier 1 AEs between vaniprevir and control.p-value: 0.25295% CI: [-5.8, 21.8]Miettinen and Nurminen method
Comparison: Difference in percentage of participants with neutropenia Tier 1 AEs between vaniprevir and control.p-value: 0.94295% CI: [-13.4, 14.4]Miettinen and Nurminen method
Secondary
Least Squares (LS) Mean Change From Baseline in HCV RNA (Log 10)
HCV RNA levels were assessed at baseline (BL) and during treatment weeks 2, 4, 8, 12, and 24 using the Roche TaqMan HCV assay, and transformed to Log 10 values. HCV RNA values below the limit of reliable quantification (LoQ) or the limit of detection (LoD) at any time point were handled as follows (imputations done for computational purposes): values below the LoQ but above the LoD were imputed with the LoQ minus 0.1; values below the LoD were imputed with the value of 0 Log IU/mL. HCV RNA levels below the LoD were considered undetectable.
Time frame: Baseline, Week 2, Week 4, Week 8, Week 12, Week 24
Population: FAS population; all randomized participants who received at least one dose of study treatment. One treated participant was excluded from the FAS due to a protocol violation.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Vaniprevir 12 Week Arm | Least Squares (LS) Mean Change From Baseline in HCV RNA (Log 10) | Change From BL at Week 12 | -6.1 Log IU/ml |
| Vaniprevir 12 Week Arm | Least Squares (LS) Mean Change From Baseline in HCV RNA (Log 10) | Change From BL at Week 8 | -6.1 Log IU/ml |
| Vaniprevir 12 Week Arm | Least Squares (LS) Mean Change From Baseline in HCV RNA (Log 10) | Change From BL at Week 2 | -5.3 Log IU/ml |
| Vaniprevir 12 Week Arm | Least Squares (LS) Mean Change From Baseline in HCV RNA (Log 10) | Change From BL at Week 4 | -6.0 Log IU/ml |
| Vaniprevir 12 Week Arm | Least Squares (LS) Mean Change From Baseline in HCV RNA (Log 10) | Change From BL at Week 24 | -6.0 Log IU/ml |
| Vaniprevir 24 Week Arm | Least Squares (LS) Mean Change From Baseline in HCV RNA (Log 10) | Change From BL at Week 8 | -6.2 Log IU/ml |
| Vaniprevir 24 Week Arm | Least Squares (LS) Mean Change From Baseline in HCV RNA (Log 10) | Change From BL at Week 2 | -5.5 Log IU/ml |
| Vaniprevir 24 Week Arm | Least Squares (LS) Mean Change From Baseline in HCV RNA (Log 10) | Change From BL at Week 4 | -6.1 Log IU/ml |
| Vaniprevir 24 Week Arm | Least Squares (LS) Mean Change From Baseline in HCV RNA (Log 10) | Change From BL at Week 12 | -6.2 Log IU/ml |
| Vaniprevir 24 Week Arm | Least Squares (LS) Mean Change From Baseline in HCV RNA (Log 10) | Change From BL at Week 24 | -6.1 Log IU/ml |
| Control Arm | Least Squares (LS) Mean Change From Baseline in HCV RNA (Log 10) | Change From BL at Week 24 | -5.3 Log IU/ml |
| Control Arm | Least Squares (LS) Mean Change From Baseline in HCV RNA (Log 10) | Change From BL at Week 12 | -4.8 Log IU/ml |
| Control Arm | Least Squares (LS) Mean Change From Baseline in HCV RNA (Log 10) | Change From BL at Week 2 | -2.0 Log IU/ml |
| Control Arm | Least Squares (LS) Mean Change From Baseline in HCV RNA (Log 10) | Change From BL at Week 8 | -4.2 Log IU/ml |
| Control Arm | Least Squares (LS) Mean Change From Baseline in HCV RNA (Log 10) | Change From BL at Week 4 | -3.0 Log IU/ml |
Comparison: Change from BL in HCV RNA at Week 2 was computed using a constrained longitudinal data analysis model including treatment, time and the interaction of time by treatment with a restriction of the same baseline mean across treatment groups as well as adjusting for IL28B and age, and their interaction terms with time will be included in the model.95% CI: [-3.5, -3]Constrained LDA Model
Comparison: Change from BL in HCV RNA at Week 2 was computed using a constrained longitudinal data analysis model including treatment, time and the interaction of time by treatment with a restriction of the same baseline mean across treatment groups as well as adjusting for IL28B and age, and their interaction terms with time will be included in the model.95% CI: [-3.7, -3.2]Constrained LDA Model
Comparison: Change from BL in HCV RNA at Week 4 was computed using a constrained longitudinal data analysis model including treatment, time and the interaction of time by treatment with a restriction of the same baseline mean across treatment groups as well as adjusting for IL28B and age, and their interaction terms with time will be included in the model.95% CI: [-3.3, -2.7]Constrained LDA Model
Comparison: Change from BL in HCV RNA at Week 4 was computed using a constrained longitudinal data analysis model including treatment, time and the interaction of time by treatment with a restriction of the same baseline mean across treatment groups as well as adjusting for IL28B and age, and their interaction terms with time will be included in the model.95% CI: [-3.4, -2.8]Constrained LDA Model
Comparison: Change from BL in HCV RNA at Week 8 was computed using a constrained longitudinal data analysis model including treatment, time and the interaction of time by treatment with a restriction of the same baseline mean across treatment groups as well as adjusting for IL28B and age, and their interaction terms with time will be included in the model.95% CI: [-2.2, -1.6]Constrained LDA Model
Comparison: Change from BL in HCV RNA at Week 8 was computed using a constrained longitudinal data analysis model including treatment, time and the interaction of time by treatment with a restriction of the same baseline mean across treatment groups as well as adjusting for IL28B and age, and their interaction terms with time will be included in the model.95% CI: [-2.3, -1.7]Constrained LDA Model
Comparison: Change from BL in HCV RNA at Week 12 was computed using a constrained longitudinal data analysis model including treatment, time and the interaction of time by treatment with a restriction of the same baseline mean across treatment groups as well as adjusting for IL28B and age, and their interaction terms with time will be included in the model.95% CI: [-1.7, -1.1]Constrained LDA Model
Comparison: Change from BL in HCV RNA at Week 12 was computed using a constrained longitudinal data analysis model including treatment, time and the interaction of time by treatment with a restriction of the same baseline mean across treatment groups as well as adjusting for IL28B and age, and their interaction terms with time will be included in the model.95% CI: [-1.7, -1.1]Constrained LDA Model
Comparison: Change from BL in HCV RNA at Week 24 was computed using a constrained longitudinal data analysis model including treatment, time and the interaction of time by treatment with a restriction of the same baseline mean across treatment groups as well as adjusting for IL28B and age, and their interaction terms with time will be included in the model.95% CI: [-1.1, -0.5]Constrained LDA Model
Comparison: Change from BL in HCV RNA at Week 24 was computed using a constrained longitudinal data analysis model including treatment, time and the interaction of time by treatment with a restriction of the same baseline mean across treatment groups as well as adjusting for IL28B and age, and their interaction terms with time will be included in the model.95% CI: [-1.2, -0.6]Constrained LDA Model
Secondary
Percentage of Participants Achieving Complete Early Virologic Response (cEVR)
cEVR was defined as having an undetectable HCV RNA level at Week 12.
Time frame: At Week 12
Population: FAS population; all randomized participants who received at least one dose of study treatment. One treated participant was excluded from the FAS due to a protocol violation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vaniprevir 12 Week Arm | Percentage of Participants Achieving Complete Early Virologic Response (cEVR) | 94.9 percentage of participants |
| Vaniprevir 24 Week Arm | Percentage of Participants Achieving Complete Early Virologic Response (cEVR) | 96.9 percentage of participants |
| Control Arm | Percentage of Participants Achieving Complete Early Virologic Response (cEVR) | 46.9 percentage of participants |
Comparison: To compare the percentage of participants achieving cEVR between the vaniprevir and control arms, 95% confidence intervals and corresponding p-values for the between-treatment difference (vaniprevir - control) were computed using Miettinen and Nurminen method stratified by IL28B and age utilizing Cochran-Mantel-Haenszel weights.p-value: <0.00195% CI: [37.2, 58.9]Miettinen and Nurminen method
Comparison: To compare the percentage of participants achieving cEVR between the vaniprevir and control arms, 95% confidence intervals and corresponding p-values for the between-treatment difference (vaniprevir - control) were computed using Miettinen and Nurminen method stratified by IL28B and age utilizing Cochran-Mantel-Haenszel weights.p-value: <0.00195% CI: [38.5, 60]Miettinen and Nurminen method
Secondary
Percentage of Participants Achieving Rapid Virologic Response (RVR)
RVR was defined as having an undetectable HCV RNA level at Week 4.
Time frame: At Week 4
Population: FAS population; all randomized participants who received at least one dose of study treatment. One treated participant was excluded from the FAS due to a protocol violation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vaniprevir 12 Week Arm | Percentage of Participants Achieving Rapid Virologic Response (RVR) | 86.7 percentage of participants |
| Vaniprevir 24 Week Arm | Percentage of Participants Achieving Rapid Virologic Response (RVR) | 85.6 percentage of participants |
| Control Arm | Percentage of Participants Achieving Rapid Virologic Response (RVR) | 9.2 percentage of participants |
Comparison: To compare the percentage of participants achieving RVR between the vaniprevir and control arms, 95% confidence intervals and corresponding p-values for the between-treatment difference (vaniprevir - control) were computed using Miettinen and Nurminen method stratified by IL28B and age utilizing Cochran-Mantel-Haenszel weights.p-value: <0.00195% CI: [68.2, 85.3]Miettinen and Nurminen method
Comparison: To compare the percentage of participants achieving RVR between the vaniprevir and control arms, 95% confidence intervals and corresponding p-values for the between-treatment difference (vaniprevir - control) were computed using Miettinen and Nurminen method stratified by IL28B and age utilizing Cochran-Mantel-Haenszel weights.p-value: <0.00195% CI: [66.7, 84.1]Miettinen and Nurminen method
Secondary
Percentage of Participants Achieving SVR12
SVR12 was defined as having an undetectable HCV RNA level 12 weeks after completion of all study therapy.
Time frame: 12 weeks after 24 or 48 weeks of study therapy (up to 60 weeks)
Population: FAS population; all randomized participants who received at least one dose of study treatment. One treated participant was excluded from the FAS due to a protocol violation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vaniprevir 12 Week Arm | Percentage of Participants Achieving SVR12 | 83.7 percentage of participants |
| Vaniprevir 24 Week Arm | Percentage of Participants Achieving SVR12 | 84.5 percentage of participants |
| Control Arm | Percentage of Participants Achieving SVR12 | 54.1 percentage of participants |
Comparison: To compare the percentage of participants achieving SVR12 between the vaniprevir and control arms, 95% confidence intervals and corresponding p-values for the between-treatment difference (vaniprevir - control) were computed using Miettinen and Nurminen method stratified by IL28B and age utilizing Cochran-Mantel-Haenszel weights.p-value: <0.00195% CI: [18.1, 41.5]Miettinen and Nurminen method
Comparison: To compare the percentage of participants achieving SVR12 between the vaniprevir and control arms, 95% confidence intervals and corresponding p-values for the between-treatment difference (vaniprevir - control) were computed using Miettinen and Nurminen method stratified by IL28B and age utilizing Cochran-Mantel-Haenszel weights.p-value: <0.00195% CI: [18.3, 41]Miettinen and Nurminen method
Secondary
Percentage of Participants Achieving Undetectable HCV RNA at the End of Treatment (EOT)
Participants were assessed for undetectable HCV RNA levels at the end of all study therapy.
Time frame: At Week 24 or 48
Population: FAS population; all randomized participants who received at least one dose of study treatment. One treated participant was excluded from the FAS due to a protocol violation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vaniprevir 12 Week Arm | Percentage of Participants Achieving Undetectable HCV RNA at the End of Treatment (EOT) | 95.9 percentage of participants |
| Vaniprevir 24 Week Arm | Percentage of Participants Achieving Undetectable HCV RNA at the End of Treatment (EOT) | 97.9 percentage of participants |
| Control Arm | Percentage of Participants Achieving Undetectable HCV RNA at the End of Treatment (EOT) | 79.6 percentage of participants |
Comparison: To compare the percentage of participants achieving undetectable HCV RNA at EOT between the vaniprevir and control arms, 95% confidence intervals and corresponding p-values for the between-treatment difference (vaniprevir - control) were computed using Miettinen and Nurminen method stratified by IL28B and age utilizing Cochran-Mantel-Haenszel weights.p-value: <0.00195% CI: [8.1, 27.3]Miettinen and Nurminen method
Comparison: To compare the percentage of participants achieving undetectable HCV RNA at EOT between the vaniprevir and control arms, 95% confidence intervals and corresponding p-values for the between-treatment difference (vaniprevir - control) were computed using Miettinen and Nurminen method stratified by IL28B and age utilizing Cochran-Mantel-Haenszel weights.p-value: <0.00195% CI: [9.3, 27.8]Miettinen and Nurminen method