Hepatitis C, Chronic
Conditions
Brief summary
This study involves treatment with boceprevir or placebo in combination with PegIntron (PEG) + Ribavirin (RBV) (weight-based dosing \[WBD\]) in previously untreated adult participants with chronic hepatitis C (CHC) genotype 1. It is hypothesized that the addition of a third active anti- Hepatitis C Virus (anti-HCV) drug may lead to more rapid viral response than therapy with two drugs, and therefore, the addition of boceprevir to PegIntron plus ribavirin therapy after a 4-week lead-in period may allow for both increased rates of sustained virologic response (SVR) and shorter treatment durations (in some populations) than treatment with PegIntron plus ribavirin alone. The study includes two separate cohorts, Cohort I (White participants) and Cohort II (Black participants). Participants from each cohort are assigned (randomized) to one of three study arms, all of which have a 4-week lead-in period with (PEG + RBV).
Detailed description
Participants from Cohort I and Cohort II are assigned (randomized) to one of three study arms, all of which have a 4-week lead-in period with (PEG + RBV). 1. Control arm, participants are treated with (PEG + RBV + placebo) for 44 weeks after the lead-in. 2. Experimental arm with Response Guided Therapy (RGT) In this experimental arm, participants are treated with all three drugs (PEG + RBV + boceprevir) for 24 weeks after the lead-in. At treatment week 28, those participants with undetectable Hepatitis C Virus - ribonucleic acid (HCV-RNA) from week 8 (up to treatment week 24), will be considered to complete treatment, and will enter follow-up. Participants with detectable for HCV-RNA at week 8 or later will receive an additional 20 weeks of therapy with PegIntron and Ribavirin (PEG + RBV + placebo). 3. Experimental arm, participants are treated with all three drugs (PEG + RBV + Ribavirin) for 44 weeks after the lead-in. All participants were followed up to 72 weeks following randomization.
Interventions
BIOLOGICALPeginterferon alfa-2b (PEG)
Peginterferon alfa-2b 1.5 μg/kg/week subcutaneously (SC)
DRUGRibavirin (RBV)
Ribavirin weight-based dosing (WBD) 600 mg/day to 1400 mg/day administered orally, divided twice daily (BID).
DRUGPlacebo
Placebo to boceprevir, 800 mg (4 x 200mg capsules) administered orally three times a day (TID).
DRUGBoceprevir
Boceprevir, 800 mg (4 x 200 mg capsules) administered orally TID.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant must have previously documented CHC genotype 1 infection. * Participant must have a liver biopsy with histology consistent with CHC and no other etiology. * Participants with bridging fibrosis or cirrhosis must have an ultrasound within 6 months of the Screening Visit (or between Screening and Day 1) with no findings suspicious for hepatocellular carcinoma (HCC). * Participant must be \>=18 years of age. * Participant must weigh between 40 kg and 125 kg. * Participant and participant's partner(s) must each agree to use acceptable methods of contraception for at least 2 weeks prior to Day 1 and continue until at least 6 months after last dose of study drug, or longer if dictated by local regulations. * Participants must be willing to give written informed consent.
Exclusion criteria
* Coinfection with the human immunodeficiency virus (HIV) or hepatitis B virus (HBsAg positive). * Participants who received prior treatment for hepatitis C; other than herbal remedies, except those with known hepatotoxicity. * Treatment with any investigational drug within 30 days of the randomization visit in this study. * Participation in any other clinical trial within 30 days of randomization or intention to participate in another clinical trial during participation in this study. * Evidence of decompensated liver disease including, but not limited to, a history or presence of clinical ascites, bleeding varices, or hepatic encephalopathy. * Diabetic and/or hypertensive participants with clinically significant ocular examination findings: retinopathy, cotton wool spots, optic nerve disorder, retinal hemorrhage, or any other clinically significant abnormality. * Pre-existing psychiatric condition(s). * Clinical diagnosis of substance abuse of the specified drugs within the specified timeframes. * Any known pre-existing medical condition that could interfere with the participant's participation in and completion of the study. * Evidence of active or suspected malignancy, or a history of malignancy, within the last 5 years (except adequately treated carcinoma in situ and basal cell carcinoma of the skin). Participants under evaluation for malignancy are not eligible. * Participants who are pregnant or nursing. Participants who intend to become pregnant during the study period. Male participants with partners who are, or intend to become, pregnant during the study period. * Any other condition which, in the opinion of a physician, would make the participant unsuitable for enrollment or could interfere with the participant participating in and completing the study. * Participants who are part of the site personnel directly involved with this study. * Participants who are family members of the investigational study staff. * Participants who had life-threatening serious adverse event (SAE) during screening period. * Protocol-specified hematologic, biochemical, and serologic criteria: Hemoglobin \<12 g/dL for females and \<13 g/dL for males; Neutrophils \<1500/mm\^3 (blacks: \<1200/mm\^3); Platelets \<100,000/mm\^3; Direct bilirubin \>1.5 x upper limit of normal (ULN) * Serum albumin \< lower limit of normal (LLN) * Thyroid-stimulating hormone (TSH) \>1.2 x ULN or \<0.8 x LLN of laboratory, with certain exceptions. * Serum creatinine \>ULN of the laboratory reference. * Protocol-specified serum glucose concentrations. * protocol-specified alpha fetoprotein levels. * Prothrombin time/partial thromboplastin time (PT/PTT) values \>10% above laboratory reference range. * Anti-nuclear antibodies (ANA) \>1:320.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sustained Virologic Response (SVR) Rate | At Follow-up Week (FW) 24 | Previously untreated adults with CHC genotype 1 were treated with the assigned study medication. Participants who had undetectable plasma HCV-RNA at FW 24 had achieved SVR. SVR rate is the percent of participants achieving SVR. HCV-RNA was detected by a nucleic acid amplification test and the limit of detection for this assay is 9.3 IU/mL. If a participant was missing data at FW 24 after having had undetectable HCV-RNA at FW 12, the participant was to be considered to have SVR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sustained Virologic Response (SVR) Rate in Participants Treated With Study Drug (Boceprevir or Placebo) | At FW 24 | Previously untreated adults with CHC genotype 1 were treated with the assigned study medication. Participants who had undetectable plasma HCV-RNA at FW 24 had achieved SVR. SVR rate was the percentage of participants treated with at least one dose of boceprevir or placebo who had achieved SVR. HCV-RNA in participant's plasma samples was detected by a nucleic acid amplification assay with a limit of detection of 9.3 IU/mL. If a participant was missing data at FW 24 after having had undetectable HCV-RNA at FW 12, the participant was to be considered to have a SVR. |
| Number of Participants With Undetectable HCV-RNA at Follow-up Week 12 and at 72 Weeks After Randomization. | At FW 12 and at 72 weeks after randomization | Previously untreated adults with CHC genotype 1 were treated with the assigned study medication. The number of participants who had undetectable plasma HCV-RNA at FW 12, and 72 weeks after randomization are reported. HCV-RNA was detected by a nucleic acid amplification test and the limit of detection for this assay is 9.3 IU/mL. |
| Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 2, 4, 8, 12, 16, or 20) | At Treatment Week 2, 4, 8, 12, 16, or 20 | Early virologic response was defined as undetectable HCV-RNA at in participants by treatment week 2, 4, 8, 12, 16, or 20. HCV-RNA in participant's plasma samples was detected by a nucleic acid amplification assay with a limit of detection of 9.3 IU/mL. |
| Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 4, 8, 12, 16, or 20) Who Achieved SVR | At Treatment Week 4, 8, 12, 16, 20 | Participants with early virologic response were those who had undetectable HCV-RNA by treatment week 4, 8, 12, 16, or 20. Participants who had undetectable plasma HCV-RNA at FW 24 had SVR. The number of participants with early virologic response that also achieved SVR is reported. HCV-RNA in participant's plasma samples was detected by a nucleic acid amplification assay with a limit of detection of 9.3 IU/mL. |
Participant flow
Recruitment details
1472 participants were enrolled in this study.
Pre-assignment details
373 participants were screened but not randomized. 1099 participants were randomized. Only 1097 received at least one dose of PegIntron (PEG) + Ribavirin (RBV) (lead-in treatment).
Participants by arm
| Arm | Count |
|---|---|
| Cohort I - 1. Placebo + PEG + RBV Cohort I (White participants) treated with PegIntron (PEG) 1.5 μg/kg + Ribavirin (RBV) (weight-based dosing \[WBD\]) for 4 weeks followed by placebo + PEG 1.5 μg/kg + RBV (WBD) for 44 weeks with 24 weeks post-treatment follow-up. | 311 |
| Cohort I - 2. Boceprevir + PEG + RBV - 24 Weeks (RGT) Cohort I (White participants) treated with PEG 1.5 μg/kg + RBV (WBD) for 4 weeks followed by boceprevir + PEG 1.5 μg/kg + RBV (WBD) for 24 weeks. Participants were offered a response guided therapy (RGT) at treatment week 28.
* At the Treatment Week 28 visit, participants whose HCV-RNA was undetectable at Treatment Week 8 and at all subsequent assays (up to Treatment Week 24), will proceed to the 44-week follow-up.
* At the Treatment Week 28 visit, participants with detectable HCV-RNA at Treatment Week 8 or at any subsequent assays will continue on therapy with placebo + PEG 1.5 μg/kg + RBV (WBD) for an additional 20 weeks, to complete a total of 48 weeks on treatment with 24 weeks post-treatment follow-up. | 316 |
| Cohort I - 3. Boceprevir + PEG + RBV - 44 Weeks Cohort I (White participants) treated with PEG 1.5 μg/kg + RBV (WBD) for 4 weeks followed by boceprevir + PEG 1.5 μg/kg + RBV (WBD) for 44 weeks with 24 weeks post-treatment follow-up. | 311 |
| Cohort II - 1. Placebo + PEG + RBV Cohort II (Black participants) treated with PegIntron (PEG) 1.5 μg/kg + Ribavirin (RBV) (weight-based dosing \[WBD\]) for 4 weeks followed by placebo + PEG 1.5 μg/kg + RBV (WBD) for 44 weeks with 24 weeks post-treatment follow-up. | 52 |
| Cohort II - 2. Boceprevir + PEG + RBV - 24 Weeks (RGT) Cohort II (Black participants) treated with PEG 1.5 μg/kg + RBV (WBD) for 4 weeks followed by boceprevir + PEG 1.5 μg/kg + RBV (WBD) for 24 weeks. Participants were offered a response guided therapy (RGT) at treatment week 28.
* At the Treatment Week 28 visit, participants whose HCV-RNA was undetectable at Treatment Week 8 and at all subsequent assays (up to Treatment Week 24), will proceed to the 44-week follow-up.
* At the Treatment Week 28 visit, participants with detectable HCV-RNA at Treatment Week 8 or at any subsequent assays will continue on therapy with placebo + PEG 1.5 μg/kg + RBV (WBD) for an additional 20 weeks, to complete a total of 48 weeks on treatment with 24 weeks post-treatment follow-up. | 52 |
| Cohort II - 3. Boceprevir + PEG + RBV - 44 Weeks Cohort II (Black participants) treated with PEG 1.5 μg/kg + RBV (WBD) for 4 weeks followed by boceprevir + PEG 1.5 μg/kg + RBV (WBD) for 44 weeks with 24 weeks post-treatment follow-up. | 55 |
| Total | 1,097 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Follow-up Period (Upto Week 72) | Adverse Event | 2 | 1 | 1 | 0 | 0 | 0 |
| Follow-up Period (Upto Week 72) | Non medical reason | 69 | 42 | 24 | 14 | 6 | 7 |
| Treatment Period | Adverse Event | 45 | 37 | 51 | 12 | 8 | 9 |
| Treatment Period | Non medical reason | 26 | 32 | 37 | 4 | 7 | 7 |
| Treatment Period | Treatment failure | 92 | 42 | 33 | 25 | 13 | 14 |
Baseline characteristics
| Characteristic | Total | Cohort I - 1. Placebo + PEG + RBV | Cohort I - 2. Boceprevir + PEG + RBV - 24 Weeks (RGT) | Cohort I - 3. Boceprevir + PEG + RBV - 44 Weeks | Cohort II - 1. Placebo + PEG + RBV | Cohort II - 2. Boceprevir + PEG + RBV - 24 Weeks (RGT) | Cohort II - 3. Boceprevir + PEG + RBV - 44 Weeks |
|---|---|---|---|---|---|---|---|
| Age, Customized >= 40 and <65 years | 905 participants | 246 participants | 261 participants | 255 participants | 45 participants | 47 participants | 51 participants |
| Age, Customized <40 years | 158 participants | 51 participants | 45 participants | 49 participants | 6 participants | 3 participants | 4 participants |
| Age, Customized >=65 years | 34 participants | 14 participants | 10 participants | 7 participants | 1 participants | 2 participants | 0 participants |
| Sex: Female, Male Female | 441 Participants | 140 Participants | 116 Participants | 123 Participants | 17 Participants | 23 Participants | 22 Participants |
| Sex: Female, Male Male | 656 Participants | 171 Participants | 200 Participants | 188 Participants | 35 Participants | 29 Participants | 33 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 | 353 / 363 | 365 / 368 | 363 / 366 |
| serious Total, serious adverse events | 31 / 363 | 42 / 368 | 45 / 366 |
Outcome results
Primary
Sustained Virologic Response (SVR) Rate
Previously untreated adults with CHC genotype 1 were treated with the assigned study medication. Participants who had undetectable plasma HCV-RNA at FW 24 had achieved SVR. SVR rate is the percent of participants achieving SVR. HCV-RNA was detected by a nucleic acid amplification test and the limit of detection for this assay is 9.3 IU/mL. If a participant was missing data at FW 24 after having had undetectable HCV-RNA at FW 12, the participant was to be considered to have SVR.
Time frame: At Follow-up Week (FW) 24
Population: Full analysis set (FAS). All randomized participants who received at least one dose of any study medication (PEG, RBV or boceprevir).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort I - 1. Placebo + PEG + RBV | Sustained Virologic Response (SVR) Rate | 40.2 Percentage of participants |
| Cohort I - 2. Boceprevir + PEG + RBV - 24 Weeks (RGT) | Sustained Virologic Response (SVR) Rate | 66.8 Percentage of participants |
| Cohort I - 3. Boceprevir + PEG + RBV - 44 Weeks | Sustained Virologic Response (SVR) Rate | 68.5 Percentage of participants |
| Cohort II - 1. Placebo + PEG + RBV | Sustained Virologic Response (SVR) Rate | 23.1 Percentage of participants |
| Cohort II - 2. Boceprevir + PEG + RBV - 24 Weeks (RGT) | Sustained Virologic Response (SVR) Rate | 42.3 Percentage of participants |
| Cohort II - 3. Boceprevir + PEG + RBV - 44 Weeks | Sustained Virologic Response (SVR) Rate | 52.7 Percentage of participants |
p-value: <0.000195% CI: [19.1, 34.1]Cochran-Mantel Haenszel Chi-square test
p-value: <0.000195% CI: [20.8, 35.8]Cochran-Mantel Haenszel Chi-square test
p-value: 0.04495% CI: [1.6, 36.9]Cochran-Mantel Haenszel Chi-square test
p-value: 0.003595% CI: [12.2, 47.1]Cochran-Mantel Haenszel Chi-square
Secondary
Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 2, 4, 8, 12, 16, or 20)
Early virologic response was defined as undetectable HCV-RNA at in participants by treatment week 2, 4, 8, 12, 16, or 20. HCV-RNA in participant's plasma samples was detected by a nucleic acid amplification assay with a limit of detection of 9.3 IU/mL.
Time frame: At Treatment Week 2, 4, 8, 12, 16, or 20
Population: Full analysis set (FAS). All randomized participants who received at least one dose of any study medication (PEG, RBV or boceprevir).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort I - 1. Placebo + PEG + RBV | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 2, 4, 8, 12, 16, or 20) | Treatment week 12 | 108 Participants |
| Cohort I - 1. Placebo + PEG + RBV | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 2, 4, 8, 12, 16, or 20) | Treatment week 16 | 138 Participants |
| Cohort I - 1. Placebo + PEG + RBV | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 2, 4, 8, 12, 16, or 20) | Treatment week 4 | 28 Participants |
| Cohort I - 1. Placebo + PEG + RBV | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 2, 4, 8, 12, 16, or 20) | Treatment week 8 | 56 Participants |
| Cohort I - 1. Placebo + PEG + RBV | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 2, 4, 8, 12, 16, or 20) | Treatment week 2 | 8 Participants |
| Cohort I - 1. Placebo + PEG + RBV | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 2, 4, 8, 12, 16, or 20) | Treatment week 20 | 157 Participants |
| Cohort I - 2. Boceprevir + PEG + RBV - 24 Weeks (RGT) | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 2, 4, 8, 12, 16, or 20) | Treatment week 2 | 11 Participants |
| Cohort I - 2. Boceprevir + PEG + RBV - 24 Weeks (RGT) | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 2, 4, 8, 12, 16, or 20) | Treatment week 4 | 18 Participants |
| Cohort I - 2. Boceprevir + PEG + RBV - 24 Weeks (RGT) | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 2, 4, 8, 12, 16, or 20) | Treatment week 16 | 231 Participants |
| Cohort I - 2. Boceprevir + PEG + RBV - 24 Weeks (RGT) | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 2, 4, 8, 12, 16, or 20) | Treatment week 12 | 237 Participants |
| Cohort I - 2. Boceprevir + PEG + RBV - 24 Weeks (RGT) | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 2, 4, 8, 12, 16, or 20) | Treatment week 20 | 231 Participants |
| Cohort I - 2. Boceprevir + PEG + RBV - 24 Weeks (RGT) | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 2, 4, 8, 12, 16, or 20) | Treatment week 8 | 190 Participants |
| Cohort I - 3. Boceprevir + PEG + RBV - 44 Weeks | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 2, 4, 8, 12, 16, or 20) | Treatment week 8 | 182 Participants |
| Cohort I - 3. Boceprevir + PEG + RBV - 44 Weeks | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 2, 4, 8, 12, 16, or 20) | Treatment week 12 | 231 Participants |
| Cohort I - 3. Boceprevir + PEG + RBV - 44 Weeks | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 2, 4, 8, 12, 16, or 20) | Treatment week 2 | 8 Participants |
| Cohort I - 3. Boceprevir + PEG + RBV - 44 Weeks | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 2, 4, 8, 12, 16, or 20) | Treatment week 4 | 20 Participants |
| Cohort I - 3. Boceprevir + PEG + RBV - 44 Weeks | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 2, 4, 8, 12, 16, or 20) | Treatment week 16 | 237 Participants |
| Cohort I - 3. Boceprevir + PEG + RBV - 44 Weeks | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 2, 4, 8, 12, 16, or 20) | Treatment week 20 | 231 Participants |
| Cohort II - 1. Placebo + PEG + RBV | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 2, 4, 8, 12, 16, or 20) | Treatment week 2 | 0 Participants |
| Cohort II - 1. Placebo + PEG + RBV | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 2, 4, 8, 12, 16, or 20) | Treatment week 4 | 2 Participants |
| Cohort II - 1. Placebo + PEG + RBV | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 2, 4, 8, 12, 16, or 20) | Treatment week 12 | 10 Participants |
| Cohort II - 1. Placebo + PEG + RBV | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 2, 4, 8, 12, 16, or 20) | Treatment week 16 | 15 Participants |
| Cohort II - 1. Placebo + PEG + RBV | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 2, 4, 8, 12, 16, or 20) | Treatment week 8 | 4 Participants |
| Cohort II - 1. Placebo + PEG + RBV | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 2, 4, 8, 12, 16, or 20) | Treatment week 20 | 15 Participants |
| Cohort II - 2. Boceprevir + PEG + RBV - 24 Weeks (RGT) | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 2, 4, 8, 12, 16, or 20) | Treatment week 12 | 25 Participants |
| Cohort II - 2. Boceprevir + PEG + RBV - 24 Weeks (RGT) | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 2, 4, 8, 12, 16, or 20) | Treatment week 20 | 27 Participants |
| Cohort II - 2. Boceprevir + PEG + RBV - 24 Weeks (RGT) | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 2, 4, 8, 12, 16, or 20) | Treatment week 16 | 26 Participants |
| Cohort II - 2. Boceprevir + PEG + RBV - 24 Weeks (RGT) | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 2, 4, 8, 12, 16, or 20) | Treatment week 8 | 18 Participants |
| Cohort II - 2. Boceprevir + PEG + RBV - 24 Weeks (RGT) | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 2, 4, 8, 12, 16, or 20) | Treatment week 2 | 1 Participants |
| Cohort II - 2. Boceprevir + PEG + RBV - 24 Weeks (RGT) | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 2, 4, 8, 12, 16, or 20) | Treatment week 4 | 1 Participants |
| Cohort II - 3. Boceprevir + PEG + RBV - 44 Weeks | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 2, 4, 8, 12, 16, or 20) | Treatment week 4 | 0 Participants |
| Cohort II - 3. Boceprevir + PEG + RBV - 44 Weeks | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 2, 4, 8, 12, 16, or 20) | Treatment week 8 | 22 Participants |
| Cohort II - 3. Boceprevir + PEG + RBV - 44 Weeks | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 2, 4, 8, 12, 16, or 20) | Treatment week 12 | 33 Participants |
| Cohort II - 3. Boceprevir + PEG + RBV - 44 Weeks | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 2, 4, 8, 12, 16, or 20) | Treatment week 2 | 0 Participants |
| Cohort II - 3. Boceprevir + PEG + RBV - 44 Weeks | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 2, 4, 8, 12, 16, or 20) | Treatment week 20 | 32 Participants |
| Cohort II - 3. Boceprevir + PEG + RBV - 44 Weeks | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 2, 4, 8, 12, 16, or 20) | Treatment week 16 | 36 Participants |
Secondary
Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 4, 8, 12, 16, or 20) Who Achieved SVR
Participants with early virologic response were those who had undetectable HCV-RNA by treatment week 4, 8, 12, 16, or 20. Participants who had undetectable plasma HCV-RNA at FW 24 had SVR. The number of participants with early virologic response that also achieved SVR is reported. HCV-RNA in participant's plasma samples was detected by a nucleic acid amplification assay with a limit of detection of 9.3 IU/mL.
Time frame: At Treatment Week 4, 8, 12, 16, 20
Population: Participants that had undetectable HCV RNA for the treatment weeks 4, 8, 12, 16, and 20.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort I - 1. Placebo + PEG + RBV | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 4, 8, 12, 16, or 20) Who Achieved SVR | Treatment week 16 (n=138, 231, 237, 15, 26, 36) | 106 Participants |
| Cohort I - 1. Placebo + PEG + RBV | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 4, 8, 12, 16, or 20) Who Achieved SVR | Treatment week 8 (n=56, 190, 182, 4, 18, 22) | 48 Participants |
| Cohort I - 1. Placebo + PEG + RBV | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 4, 8, 12, 16, or 20) Who Achieved SVR | Treatment week 4 (n=28, 18, 20, 2, 1, 0) | 27 Participants |
| Cohort I - 1. Placebo + PEG + RBV | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 4, 8, 12, 16, or 20) Who Achieved SVR | Treatment week 20 (n=157, 231, 231, 15, 27, 32) | 118 Participants |
| Cohort I - 1. Placebo + PEG + RBV | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 4, 8, 12, 16, or 20) Who Achieved SVR | Treatment week 12 (n=108, 237, 231, 10, 25, 33) | 90 Participants |
| Cohort I - 2. Boceprevir + PEG + RBV - 24 Weeks (RGT) | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 4, 8, 12, 16, or 20) Who Achieved SVR | Treatment week 8 (n=56, 190, 182, 4, 18, 22) | 170 Participants |
| Cohort I - 2. Boceprevir + PEG + RBV - 24 Weeks (RGT) | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 4, 8, 12, 16, or 20) Who Achieved SVR | Treatment week 16 (n=138, 231, 237, 15, 26, 36) | 205 Participants |
| Cohort I - 2. Boceprevir + PEG + RBV - 24 Weeks (RGT) | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 4, 8, 12, 16, or 20) Who Achieved SVR | Treatment week 4 (n=28, 18, 20, 2, 1, 0) | 16 Participants |
| Cohort I - 2. Boceprevir + PEG + RBV - 24 Weeks (RGT) | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 4, 8, 12, 16, or 20) Who Achieved SVR | Treatment week 20 (n=157, 231, 231, 15, 27, 32) | 201 Participants |
| Cohort I - 2. Boceprevir + PEG + RBV - 24 Weeks (RGT) | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 4, 8, 12, 16, or 20) Who Achieved SVR | Treatment week 12 (n=108, 237, 231, 10, 25, 33) | 205 Participants |
| Cohort I - 3. Boceprevir + PEG + RBV - 44 Weeks | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 4, 8, 12, 16, or 20) Who Achieved SVR | Treatment week 8 (n=56, 190, 182, 4, 18, 22) | 166 Participants |
| Cohort I - 3. Boceprevir + PEG + RBV - 44 Weeks | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 4, 8, 12, 16, or 20) Who Achieved SVR | Treatment week 16 (n=138, 231, 237, 15, 26, 36) | 210 Participants |
| Cohort I - 3. Boceprevir + PEG + RBV - 44 Weeks | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 4, 8, 12, 16, or 20) Who Achieved SVR | Treatment week 20 (n=157, 231, 231, 15, 27, 32) | 208 Participants |
| Cohort I - 3. Boceprevir + PEG + RBV - 44 Weeks | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 4, 8, 12, 16, or 20) Who Achieved SVR | Treatment week 12 (n=108, 237, 231, 10, 25, 33) | 204 Participants |
| Cohort I - 3. Boceprevir + PEG + RBV - 44 Weeks | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 4, 8, 12, 16, or 20) Who Achieved SVR | Treatment week 4 (n=28, 18, 20, 2, 1, 0) | 18 Participants |
| Cohort II - 1. Placebo + PEG + RBV | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 4, 8, 12, 16, or 20) Who Achieved SVR | Treatment week 12 (n=108, 237, 231, 10, 25, 33) | 7 Participants |
| Cohort II - 1. Placebo + PEG + RBV | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 4, 8, 12, 16, or 20) Who Achieved SVR | Treatment week 4 (n=28, 18, 20, 2, 1, 0) | 2 Participants |
| Cohort II - 1. Placebo + PEG + RBV | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 4, 8, 12, 16, or 20) Who Achieved SVR | Treatment week 8 (n=56, 190, 182, 4, 18, 22) | 3 Participants |
| Cohort II - 1. Placebo + PEG + RBV | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 4, 8, 12, 16, or 20) Who Achieved SVR | Treatment week 16 (n=138, 231, 237, 15, 26, 36) | 12 Participants |
| Cohort II - 1. Placebo + PEG + RBV | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 4, 8, 12, 16, or 20) Who Achieved SVR | Treatment week 20 (n=157, 231, 231, 15, 27, 32) | 12 Participants |
| Cohort II - 2. Boceprevir + PEG + RBV - 24 Weeks (RGT) | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 4, 8, 12, 16, or 20) Who Achieved SVR | Treatment week 16 (n=138, 231, 237, 15, 26, 36) | 20 Participants |
| Cohort II - 2. Boceprevir + PEG + RBV - 24 Weeks (RGT) | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 4, 8, 12, 16, or 20) Who Achieved SVR | Treatment week 4 (n=28, 18, 20, 2, 1, 0) | 1 Participants |
| Cohort II - 2. Boceprevir + PEG + RBV - 24 Weeks (RGT) | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 4, 8, 12, 16, or 20) Who Achieved SVR | Treatment week 20 (n=157, 231, 231, 15, 27, 32) | 21 Participants |
| Cohort II - 2. Boceprevir + PEG + RBV - 24 Weeks (RGT) | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 4, 8, 12, 16, or 20) Who Achieved SVR | Treatment week 8 (n=56, 190, 182, 4, 18, 22) | 14 Participants |
| Cohort II - 2. Boceprevir + PEG + RBV - 24 Weeks (RGT) | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 4, 8, 12, 16, or 20) Who Achieved SVR | Treatment week 12 (n=108, 237, 231, 10, 25, 33) | 19 Participants |
| Cohort II - 3. Boceprevir + PEG + RBV - 44 Weeks | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 4, 8, 12, 16, or 20) Who Achieved SVR | Treatment week 4 (n=28, 18, 20, 2, 1, 0) | 0 Participants |
| Cohort II - 3. Boceprevir + PEG + RBV - 44 Weeks | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 4, 8, 12, 16, or 20) Who Achieved SVR | Treatment week 16 (n=138, 231, 237, 15, 26, 36) | 26 Participants |
| Cohort II - 3. Boceprevir + PEG + RBV - 44 Weeks | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 4, 8, 12, 16, or 20) Who Achieved SVR | Treatment week 8 (n=56, 190, 182, 4, 18, 22) | 18 Participants |
| Cohort II - 3. Boceprevir + PEG + RBV - 44 Weeks | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 4, 8, 12, 16, or 20) Who Achieved SVR | Treatment week 20 (n=157, 231, 231, 15, 27, 32) | 26 Participants |
| Cohort II - 3. Boceprevir + PEG + RBV - 44 Weeks | Number of Participants With Early Virologic Response (Undetectable HCV-RNA at Treatment Week 4, 8, 12, 16, or 20) Who Achieved SVR | Treatment week 12 (n=108, 237, 231, 10, 25, 33) | 26 Participants |
Secondary
Number of Participants With Undetectable HCV-RNA at Follow-up Week 12 and at 72 Weeks After Randomization.
Previously untreated adults with CHC genotype 1 were treated with the assigned study medication. The number of participants who had undetectable plasma HCV-RNA at FW 12, and 72 weeks after randomization are reported. HCV-RNA was detected by a nucleic acid amplification test and the limit of detection for this assay is 9.3 IU/mL.
Time frame: At FW 12 and at 72 weeks after randomization
Population: Full analysis set (FAS). All randomized participants who received at least one dose of any study medication (PEG, RBV or boceprevir).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort I - 1. Placebo + PEG + RBV | Number of Participants With Undetectable HCV-RNA at Follow-up Week 12 and at 72 Weeks After Randomization. | At follow-up week 12 | 127 Participants |
| Cohort I - 1. Placebo + PEG + RBV | Number of Participants With Undetectable HCV-RNA at Follow-up Week 12 and at 72 Weeks After Randomization. | 72 weeks after randomization | 120 Participants |
| Cohort I - 2. Boceprevir + PEG + RBV - 24 Weeks (RGT) | Number of Participants With Undetectable HCV-RNA at Follow-up Week 12 and at 72 Weeks After Randomization. | At follow-up week 12 | 209 Participants |
| Cohort I - 2. Boceprevir + PEG + RBV - 24 Weeks (RGT) | Number of Participants With Undetectable HCV-RNA at Follow-up Week 12 and at 72 Weeks After Randomization. | 72 weeks after randomization | 194 Participants |
| Cohort I - 3. Boceprevir + PEG + RBV - 44 Weeks | Number of Participants With Undetectable HCV-RNA at Follow-up Week 12 and at 72 Weeks After Randomization. | At follow-up week 12 | 209 Participants |
| Cohort I - 3. Boceprevir + PEG + RBV - 44 Weeks | Number of Participants With Undetectable HCV-RNA at Follow-up Week 12 and at 72 Weeks After Randomization. | 72 weeks after randomization | 205 Participants |
| Cohort II - 1. Placebo + PEG + RBV | Number of Participants With Undetectable HCV-RNA at Follow-up Week 12 and at 72 Weeks After Randomization. | At follow-up week 12 | 11 Participants |
| Cohort II - 1. Placebo + PEG + RBV | Number of Participants With Undetectable HCV-RNA at Follow-up Week 12 and at 72 Weeks After Randomization. | 72 weeks after randomization | 11 Participants |
| Cohort II - 2. Boceprevir + PEG + RBV - 24 Weeks (RGT) | Number of Participants With Undetectable HCV-RNA at Follow-up Week 12 and at 72 Weeks After Randomization. | At follow-up week 12 | 21 Participants |
| Cohort II - 2. Boceprevir + PEG + RBV - 24 Weeks (RGT) | Number of Participants With Undetectable HCV-RNA at Follow-up Week 12 and at 72 Weeks After Randomization. | 72 weeks after randomization | 20 Participants |
| Cohort II - 3. Boceprevir + PEG + RBV - 44 Weeks | Number of Participants With Undetectable HCV-RNA at Follow-up Week 12 and at 72 Weeks After Randomization. | At follow-up week 12 | 29 Participants |
| Cohort II - 3. Boceprevir + PEG + RBV - 44 Weeks | Number of Participants With Undetectable HCV-RNA at Follow-up Week 12 and at 72 Weeks After Randomization. | 72 weeks after randomization | 27 Participants |
Secondary
Sustained Virologic Response (SVR) Rate in Participants Treated With Study Drug (Boceprevir or Placebo)
Previously untreated adults with CHC genotype 1 were treated with the assigned study medication. Participants who had undetectable plasma HCV-RNA at FW 24 had achieved SVR. SVR rate was the percentage of participants treated with at least one dose of boceprevir or placebo who had achieved SVR. HCV-RNA in participant's plasma samples was detected by a nucleic acid amplification assay with a limit of detection of 9.3 IU/mL. If a participant was missing data at FW 24 after having had undetectable HCV-RNA at FW 12, the participant was to be considered to have a SVR.
Time frame: At FW 24
Population: Modified intent-to-treat set (mITT). All randomized participants who received at least one dose of boceprevir or placebo.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort I - 1. Placebo + PEG + RBV | Sustained Virologic Response (SVR) Rate in Participants Treated With Study Drug (Boceprevir or Placebo) | 42.1 Percentage of participants |
| Cohort I - 2. Boceprevir + PEG + RBV - 24 Weeks (RGT) | Sustained Virologic Response (SVR) Rate in Participants Treated With Study Drug (Boceprevir or Placebo) | 69.6 Percentage of participants |
| Cohort I - 3. Boceprevir + PEG + RBV - 44 Weeks | Sustained Virologic Response (SVR) Rate in Participants Treated With Study Drug (Boceprevir or Placebo) | 71.2 Percentage of participants |
| Cohort II - 1. Placebo + PEG + RBV | Sustained Virologic Response (SVR) Rate in Participants Treated With Study Drug (Boceprevir or Placebo) | 25.5 Percentage of participants |
| Cohort II - 2. Boceprevir + PEG + RBV - 24 Weeks (RGT) | Sustained Virologic Response (SVR) Rate in Participants Treated With Study Drug (Boceprevir or Placebo) | 46.8 Percentage of participants |
| Cohort II - 3. Boceprevir + PEG + RBV - 44 Weeks | Sustained Virologic Response (SVR) Rate in Participants Treated With Study Drug (Boceprevir or Placebo) | 52.7 Percentage of participants |
p-value: <0.000195% CI: [19.2, 35.2]Cochran-Mantel Haenszel Chi-square
p-value: <0.000195% CI: [21.5, 36.8]Cochran-Mantel Haenszel Chi-square
p-value: 0.036695% CI: [2.3, 40.2]Cochran-Mantel Haenszel Chi-square test
p-value: 0.010795% CI: [9, 45.3]Cochran-Mantel Haenszel Chi-square