Chronic Hepatitis C
Conditions
Brief summary
This was an open-label, randomized safety and efficacy trial in adult, treatment-naïve Chronic Hepatitis C (CHC) participants with genotype 1 infection. The study conducted in 2 parts, compared standard-of-care PegIntron (1.5 μg/kg, once weekly \[QW\]), plus ribavirin (800 to 1400 mg/day), for 48 weeks to five treatment paradigms containing boceprevir (SCH 503034) 800 mg thrice a day (TID). The five treatments included boceprevir (BOC) plus standard-of-care for 28 or 48 weeks, with and without a 4-week lead-in with PegIntron (PEG) and ribavirin (RBV), and exploration of PegIntron plus low-dose ribavirin (400 to 1000 mg/day) plus boceprevir for 48 weeks.
Detailed description
The study was conducted in 2 parts. Part 1 of the study had 5 arms using weight based ribavirin 800-1400 mg/day and compared: * PegIntron and ribavirin for 48 weeks (Arm 1 - Control) * PegIntron, ribavirin, and boceprevir for 28 weeks (Arm 2) * Lead-in with PegIntron and ribavirin for 4 weeks followed by PegIntron, ribavirin and boceprevir for 24 weeks (Arm 3) * PegIntron, ribavirin and boceprevir for 48 weeks (Arm 4) * Lead-in with PegIntron and ribavirin for 4 weeks, followed by PegIntron, ribavirin and boceprevir for 44 weeks (Arm 5) Participants from Arm 1 receiving PegIntron and ribavirin that were HCV positive after 24 weeks of treatment had the option to receive boceprevir in combination with PegIntron and ribavirin for an additional 24 weeks. All participants from Arm 1 that started boceprevir after Week 24 formed the crossover arm (Arm 8). Part 2 of the study assessed the safety and efficacy of low dose ribavirin (400-1000 mg/day) and compared: * PegIntron, ribavirin (800-1400 mg/day) and boceprevir for 48 weeks (Arm 6) * PegIntron, low-dose ribavirin (400-1000 mg/day) and boceprevir for 48 weeks (Arm 7) Follow-up for all participants was up to 72 weeks after randomization.
Interventions
200 mg capsules taken as 800 mg orally three times daily (TID)
DRUGpeginterferon-alfa 2b (PegIntron)
1.5 μg/kg subcutaneously (SC) once weekly (QW)
DRUGribavirin
200 mg capsules in doses of 800 to 1400 mg/day (based on weight) taken orally divided twice daily
DRUGribavirin (low-dose)
200 mg capsules in doses of 400 to 1000 mg/day (based on weight) taken orally divided twice daily
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Age between 18 and 60 years; * Body weight between 45 and 125 kg; * Documented chronic hepatitis C genotype 1; * Liver biopsy with histology consistent with chronic hepatitis and no other etiology for chronic liver disease within of 5 years of Day 1; * Participant and participant's partner(s) must each agree to use acceptable methods of contraception 2 weeks prior to Day 1 and at least 6 months after the last dose of study medication; * Written informed consent.
Exclusion criteria
Include, but are not limited to, the following: * Prior treatment for hepatitis C; * Co-infection with HIV or hepatitis B virus (HBsAg positive); * Evidence of decompensated liver disease; * Diabetic and hypertensive participants with clinically significant ocular exam findings; * Pre-existing psychiatric condition, including but not limited to: * Current moderate or severe depression; * History of depression associated with any of the following: * Hospitalization for depression; * Electroconvulsive therapy for depression; * Depression that resulted in a prolonged absence from work and/or significant disruption of daily functions; * Suicidal or homicidal ideation and/or attempt; * History of severe psychiatric disorders (including but not limited to schizophrenia, psychosis, bipolar disorder, post-traumatic stress disorder or mania); * Past history or current use of lithium; * Past history or current use of antipsychotic drugs for listed conditions. * Substance abuse within protocol specified timeframes; * Pre-existing medical conditions that could interfere with the participant's participation in and completion of the study, including but not limited to chronic pulmonary disease, cardiac dysfunction or immunologically-mediated disease; * Active or suspected malignancy or history of malignancy within the past 5 years; * 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. * Treatment with any investigational drug or participation in any clinical trial 30 days within Screening; * 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; * Other clinically significant laboratory test abnormalities.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Sustained Virologic Response (SVR) | From follow-up week (FW) 24 up to end of follow-up (EOF) | Participants with undetectable HCV-RNA at FW 24 up to EOF had achieved SVR. Participants missing data at FW 24 were considered to achieve SVR if 1. he/she had undetectable HCV-RNA at FW 12 or later 2. he/she returned later to the study center and had undetectable HCV-RNA. HCV-RNA in plasma samples was detected with reverse-transcriptase-polymerase chain reaction (RT-PCR) assay, with a lower limit of detection (LLD) of 29 international units/mL (IU/mL). A participant in Arm 2 with undetectable HCV-RNA at FW 24 had detectable HCV-RNA after FW 24. He is not considered to achieve SVR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With SVR Based on Duration of Boceprevir Treatment | From FW 24 up to EOF | Number of participants with SVR (undetectable plasma HCV-RNA at FW 24 up to EOF). Participants from treatment arms receiving boceprevir for 28-weeks (Arm 2 and Arm 3) were pooled, and those receiving boceprevir for 48-weeks (Arm 4 and Arm 5) were pooled for the analysis. Participants missing data at FW 24 were considered to achieve SVR if 1. he/she had undetectable HCV-RNA at FW 12 or later 2. he/she returned later to the study center and had undetectable HCV-RNA. HCV-RNA in plasma samples was detected with an RT-PCR assay. The LLD for the assay was 29 IU/mL. |
| Number of Participants Negative for HCV-RNA at FW 12 | At FW 12 | Participants who had undetectable plasma HCV-RNA at FW 12. Also reported are participants for whom the HCV-RNA values were missing. 36 participant who switched over to Arm 8 from Arm 1, are included in the missing values for Arm 1. HCV-RNA in plasma samples was detected with an RT-PCR assay. The LLD for the assay was 29 IU/mL. |
| Number of Participants Negative for HCV-RNA at 72 Weeks Post Randomization | 72 weeks post randomization | Participants who had undetectable HCV-RNA at 72 weeks post randomization are reported. Participants with missing HCV-RNA values at 72 weeks post randomization are also reported. HCV-RNA in plasma samples was detected with an RT-PCR assay. The LLD for the assay was 29 IU/mL. |
| Number of Participants With SVR Based on a 4-week lead-in Treatment With PegIntron and Ribavirin | From FW 24 up to EOF | Number of participants with SVR (undetectable plasma HCV-RNA at FW 24 up to EOF). To assess the effect of lead-in treatment on SVR, participants with (Arm 3 and Arm 5) or without (Arm 2 and Arm 4) lead-in were pooled. Participants missing data at FW 24 were considered to achieve SVR if 1. he/she had undetectable HCV-RNA at FW 12 or later 2. he/she returned later to the study center and had undetectable HCV-RNA. HCV-RNA in plasma samples was detected with an RT-PCR assay. The LLD for the assay was 29 IU/mL. |
| Number of Participants With a Virologic Response at Follow-up Week 12 That Achieved SVR | At FW 12 and FW 24 up to EOF | Treatment-naïve adults with CHC genotype 1 were assigned study medication. Participants with undetectable HCV-RNA at FW 12 that achieved SVR (have undetectable HCV-RNA at FW 24 (up to EOF) are reported. Participants missing data at FW 24 were considered to achieve SVR if 1. he/she had undetectable HCV-RNA at FW 12 or later 2. if he/she returned later to the study center and had undetectable HCV-RNA. HCV-RNA in plasma samples was detected with an RT-PCR assay. The LLD for the assay was 29 IU/mL. |
| Number of Participants With a Virologic Response at 72 Weeks Post Randomization That Achieved SVR | At FW 24 up to EOF and at 72 weeks post randomization | Participants with undetectable HCV-RNA at 72 weeks post randomization that achieved SVR (have undetectable HCV-RNA at FW 24 up to EOF) are reported. Participants missing data at FW 24 were considered to achieve SVR if 1. he/she had undetectable HCV-RNA at FW 12 or later 2. if he/she returned later to the study center and had undetectable HCV-RNA. HCV-RNA in plasma samples was detected an the RT-PCR assay. The lower limit of detection (LLD) was 29 IU/mL. |
| Number of Participants With an Early Virologic Response (EVR) That Achieved SVR | At TW 12, and at FW 24 up to EOF | Participants with undetectable HCV-RNA at TW 12 have EVR, and with undetectable HCV-RNA at FW 24 (up to EOF) achieved SVR. Participants missing data at FW 24 were considered to achieve SVR if 1. he/she had undetectable HCV-RNA at FW 12 or later 2. if he/she returned later to the study center and had undetectable HCV-RNA. HCV-RNA in plasma samples was detected with an RT-PCR assay. The LLD for the assay was 29 IU/mL. |
Participant flow
Recruitment details
765 participants were screened in the study, 598 were randomized of which 3 participants were not treated (Arm 1-7). Participants were assigned to Part I (with standard dosing for ribavirin) or Part II (to explore low-dose ribavirin). All participants that completed or discontinued treatment were scheduled to enter follow-up phase per protocol.
Pre-assignment details
Participants in Arm 1 (Part I) who had detectable Hepatitis C Virus-ribonucleic acid (HCV-RNA) at Treatment Week (TW) 24 were offered boceprevir in addition to PegIntron and ribavirin for an additional 24 weeks of treatment, and switched to a new arm, Arm 8.
Participants by arm
| Arm | Count |
|---|---|
| Arm 1. PEG +RBV for 48 Wks (Part I) PegIntron (1.5 μg/kg QW) plus ribavirin (800 to 1400 mg/day) for 48 weeks.
• Participants with detectable HCV-RNA levels after 24 weeks of treatment had to receive 24 weeks of PegIntron, ribavirin and boceprevir (800 mg TID) for 24 additional weeks. Total treatment duration was up to 54 weeks. | 104 |
| Arm 2. PEG + RBV + BOC for 28 Wks (Part I) Boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 28 weeks. | 107 |
| Arm 3. PEG + RBV + BOC (From Wk 4) for 24 Wks (Part I) PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for 4 weeks lead in followed by boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 24 weeks. | 103 |
| Arm 4. PEG +RBV + BOC for 48 Wks (Part I) Boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 48 weeks. | 103 |
| Arm 5. PEG + RBV+ BOC (From Wk 4) for 44 Wks (Part I) PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for 4 weeks lead in followed by boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 44 weeks. | 103 |
| Arm 6. PEG + RBV + BOC for 48 Wks (Part II) PegIntron (1.5 μg/kg QW), ribavirin (800 to 1400 mg/day) and boceprevir (800 mg TID) for up to 48 weeks. | 16 |
| Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II) PegIntron (1.5 μg/kg QW), ribavirin (400 to 1000 mg/day) and boceprevir (800 mg TID) for up to 48 weeks. | 59 |
| Total | 595 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Follow-up Period | Lost to Follow-up | 0 | 12 | 8 | 3 | 1 | 0 | 5 | 0 |
| Follow-up Period | Non-compliance with protocol | 2 | 0 | 1 | 1 | 0 | 0 | 3 | 2 |
| Follow-up Period | Subject withdrew (not treatment related) | 1 | 4 | 2 | 1 | 1 | 0 | 1 | 1 |
| Treatment Period | Adverse Event | 8 | 12 | 15 | 20 | 9 | 4 | 7 | 2 |
| Treatment Period | Investigator decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Treatment Period | Lost to Follow-up | 2 | 1 | 3 | 1 | 6 | 0 | 3 | 1 |
| Treatment Period | Non-compliance with protocol | 3 | 1 | 1 | 3 | 2 | 0 | 2 | 2 |
| Treatment Period | Protocol-defined clinical event | 0 | 7 | 4 | 12 | 5 | 4 | 16 | 15 |
| Treatment Period | Subject withdrew (not treatment related) | 3 | 9 | 4 | 4 | 5 | 0 | 3 | 0 |
| Treatment Period | Switched to Arm 8 at TW 24 | 36 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Arm 1. PEG +RBV for 48 Wks (Part I) | Arm 2. PEG + RBV + BOC for 28 Wks (Part I) | Arm 3. PEG + RBV + BOC (From Wk 4) for 24 Wks (Part I) | Arm 4. PEG +RBV + BOC for 48 Wks (Part I) | Arm 5. PEG + RBV+ BOC (From Wk 4) for 44 Wks (Part I) | Arm 6. PEG + RBV + BOC for 48 Wks (Part II) | Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II) | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 48.3 years STANDARD_DEVIATION 6.9 | 46.4 years STANDARD_DEVIATION 8 | 47.7 years STANDARD_DEVIATION 7.4 | 46.7 years STANDARD_DEVIATION 8.8 | 47.6 years STANDARD_DEVIATION 8.3 | 50.3 years STANDARD_DEVIATION 8.5 | 48.7 years STANDARD_DEVIATION 5.8 | 47.5 years STANDARD_DEVIATION 7.7 |
| Sex: Female, Male Female | 34 Participants | 44 Participants | 52 Participants | 40 Participants | 45 Participants | 7 Participants | 18 Participants | 240 Participants |
| Sex: Female, Male Male | 70 Participants | 63 Participants | 51 Participants | 63 Participants | 58 Participants | 9 Participants | 41 Participants | 355 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 | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 102 / 104 | 106 / 107 | 102 / 103 | 103 / 103 | 102 / 103 | 16 / 16 | 59 / 59 | 29 / 36 |
| serious Total, serious adverse events | 8 / 104 | 10 / 107 | 8 / 103 | 10 / 103 | 6 / 103 | 1 / 16 | 3 / 59 | 2 / 36 |
Outcome results
Primary
Number of Participants With Sustained Virologic Response (SVR)
Participants with undetectable HCV-RNA at FW 24 up to EOF had achieved SVR. Participants missing data at FW 24 were considered to achieve SVR if 1. he/she had undetectable HCV-RNA at FW 12 or later 2. he/she returned later to the study center and had undetectable HCV-RNA. HCV-RNA in plasma samples was detected with reverse-transcriptase-polymerase chain reaction (RT-PCR) assay, with a lower limit of detection (LLD) of 29 international units/mL (IU/mL). A participant in Arm 2 with undetectable HCV-RNA at FW 24 had detectable HCV-RNA after FW 24. He is not considered to achieve SVR.
Time frame: From follow-up week (FW) 24 up to end of follow-up (EOF)
Population: Intent-to-Treat (ITT) population: All randomized participants who received at least one dose of any study medication (PegIntron, ribavirin, or boceprevir).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1. PEG +RBV for 48 Wks (Part I) | Number of Participants With Sustained Virologic Response (SVR) | 39 Participants |
| Arm 2. PEG + RBV + BOC for 28 Wks (Part I) | Number of Participants With Sustained Virologic Response (SVR) | 58 Participants |
| Arm 3. PEG + RBV + BOC (From Wk 4) for 24 Wks (Part I) | Number of Participants With Sustained Virologic Response (SVR) | 58 Participants |
| Arm 4. PEG +RBV + BOC for 48 Wks (Part I) | Number of Participants With Sustained Virologic Response (SVR) | 69 Participants |
| Arm 5. PEG + RBV+ BOC (From Wk 4) for 44 Wks (Part I) | Number of Participants With Sustained Virologic Response (SVR) | 77 Participants |
| Arm 6. PEG + RBV + BOC for 48 Wks (Part II) | Number of Participants With Sustained Virologic Response (SVR) | 8 Participants |
| Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II) | Number of Participants With Sustained Virologic Response (SVR) | 21 Participants |
p-value: 0.012695% CI: [3.5, 30]Cochran-Mantel Haenszel Chi-square test
p-value: 0.004895% CI: [5.5, 32.2]Cochran-Mantel Haenszel Chi-square test
p-value: <0.000195% CI: [16.5, 42.5]Cochran-Mantel Haenszel Chi-square test
p-value: <0.000195% CI: [24.7, 49.8]Cochran-Mantel Haenszel Chi-square test
Secondary
Number of Participants Negative for HCV-RNA at 72 Weeks Post Randomization
Participants who had undetectable HCV-RNA at 72 weeks post randomization are reported. Participants with missing HCV-RNA values at 72 weeks post randomization are also reported. HCV-RNA in plasma samples was detected with an RT-PCR assay. The LLD for the assay was 29 IU/mL.
Time frame: 72 weeks post randomization
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 1. PEG +RBV for 48 Wks (Part I) | Number of Participants Negative for HCV-RNA at 72 Weeks Post Randomization | HCV-RNA negative | 38 Participants |
| Arm 1. PEG +RBV for 48 Wks (Part I) | Number of Participants Negative for HCV-RNA at 72 Weeks Post Randomization | Missing HCV-RNA at 72 weeks post randomization | 45 Participants |
| Arm 2. PEG + RBV + BOC for 28 Wks (Part I) | Number of Participants Negative for HCV-RNA at 72 Weeks Post Randomization | HCV-RNA negative | 53 Participants |
| Arm 2. PEG + RBV + BOC for 28 Wks (Part I) | Number of Participants Negative for HCV-RNA at 72 Weeks Post Randomization | Missing HCV-RNA at 72 weeks post randomization | 25 Participants |
| Arm 3. PEG + RBV + BOC (From Wk 4) for 24 Wks (Part I) | Number of Participants Negative for HCV-RNA at 72 Weeks Post Randomization | HCV-RNA negative | 56 Participants |
| Arm 3. PEG + RBV + BOC (From Wk 4) for 24 Wks (Part I) | Number of Participants Negative for HCV-RNA at 72 Weeks Post Randomization | Missing HCV-RNA at 72 weeks post randomization | 18 Participants |
| Arm 4. PEG +RBV + BOC for 48 Wks (Part I) | Number of Participants Negative for HCV-RNA at 72 Weeks Post Randomization | Missing HCV-RNA at 72 weeks post randomization | 17 Participants |
| Arm 4. PEG +RBV + BOC for 48 Wks (Part I) | Number of Participants Negative for HCV-RNA at 72 Weeks Post Randomization | HCV-RNA negative | 67 Participants |
| Arm 5. PEG + RBV+ BOC (From Wk 4) for 44 Wks (Part I) | Number of Participants Negative for HCV-RNA at 72 Weeks Post Randomization | HCV-RNA negative | 76 Participants |
| Arm 5. PEG + RBV+ BOC (From Wk 4) for 44 Wks (Part I) | Number of Participants Negative for HCV-RNA at 72 Weeks Post Randomization | Missing HCV-RNA at 72 weeks post randomization | 20 Participants |
| Arm 6. PEG + RBV + BOC for 48 Wks (Part II) | Number of Participants Negative for HCV-RNA at 72 Weeks Post Randomization | HCV-RNA negative | 8 Participants |
| Arm 6. PEG + RBV + BOC for 48 Wks (Part II) | Number of Participants Negative for HCV-RNA at 72 Weeks Post Randomization | Missing HCV-RNA at 72 weeks post randomization | 6 Participants |
| Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II) | Number of Participants Negative for HCV-RNA at 72 Weeks Post Randomization | Missing HCV-RNA at 72 weeks post randomization | 22 Participants |
| Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II) | Number of Participants Negative for HCV-RNA at 72 Weeks Post Randomization | HCV-RNA negative | 20 Participants |
Secondary
Number of Participants Negative for HCV-RNA at FW 12
Participants who had undetectable plasma HCV-RNA at FW 12. Also reported are participants for whom the HCV-RNA values were missing. 36 participant who switched over to Arm 8 from Arm 1, are included in the missing values for Arm 1. HCV-RNA in plasma samples was detected with an RT-PCR assay. The LLD for the assay was 29 IU/mL.
Time frame: At FW 12
Population: Intent-to-Treat (ITT) population: All randomized participants who received at least one dose of any study medication (PegIntron, ribavirin, or boceprevir).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 1. PEG +RBV for 48 Wks (Part I) | Number of Participants Negative for HCV-RNA at FW 12 | HCV-RNA negative | 39 Participants |
| Arm 1. PEG +RBV for 48 Wks (Part I) | Number of Participants Negative for HCV-RNA at FW 12 | Missing HCV-RNA at FW 12 | 42 Participants |
| Arm 2. PEG + RBV + BOC for 28 Wks (Part I) | Number of Participants Negative for HCV-RNA at FW 12 | HCV-RNA negative | 60 Participants |
| Arm 2. PEG + RBV + BOC for 28 Wks (Part I) | Number of Participants Negative for HCV-RNA at FW 12 | Missing HCV-RNA at FW 12 | 13 Participants |
| Arm 3. PEG + RBV + BOC (From Wk 4) for 24 Wks (Part I) | Number of Participants Negative for HCV-RNA at FW 12 | HCV-RNA negative | 59 Participants |
| Arm 3. PEG + RBV + BOC (From Wk 4) for 24 Wks (Part I) | Number of Participants Negative for HCV-RNA at FW 12 | Missing HCV-RNA at FW 12 | 11 Participants |
| Arm 4. PEG +RBV + BOC for 48 Wks (Part I) | Number of Participants Negative for HCV-RNA at FW 12 | HCV-RNA negative | 69 Participants |
| Arm 4. PEG +RBV + BOC for 48 Wks (Part I) | Number of Participants Negative for HCV-RNA at FW 12 | Missing HCV-RNA at FW 12 | 12 Participants |
| Arm 5. PEG + RBV+ BOC (From Wk 4) for 44 Wks (Part I) | Number of Participants Negative for HCV-RNA at FW 12 | HCV-RNA negative | 76 Participants |
| Arm 5. PEG + RBV+ BOC (From Wk 4) for 44 Wks (Part I) | Number of Participants Negative for HCV-RNA at FW 12 | Missing HCV-RNA at FW 12 | 14 Participants |
| Arm 6. PEG + RBV + BOC for 48 Wks (Part II) | Number of Participants Negative for HCV-RNA at FW 12 | HCV-RNA negative | 8 Participants |
| Arm 6. PEG + RBV + BOC for 48 Wks (Part II) | Number of Participants Negative for HCV-RNA at FW 12 | Missing HCV-RNA at FW 12 | 2 Participants |
| Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II) | Number of Participants Negative for HCV-RNA at FW 12 | HCV-RNA negative | 21 Participants |
| Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II) | Number of Participants Negative for HCV-RNA at FW 12 | Missing HCV-RNA at FW 12 | 17 Participants |
Secondary
Number of Participants With an Early Virologic Response (EVR) That Achieved SVR
Participants with undetectable HCV-RNA at TW 12 have EVR, and with undetectable HCV-RNA at FW 24 (up to EOF) achieved SVR. Participants missing data at FW 24 were considered to achieve SVR if 1. he/she had undetectable HCV-RNA at FW 12 or later 2. if he/she returned later to the study center and had undetectable HCV-RNA. HCV-RNA in plasma samples was detected with an RT-PCR assay. The LLD for the assay was 29 IU/mL.
Time frame: At TW 12, and at FW 24 up to EOF
Population: Participants with an early virologic response (EVR).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1. PEG +RBV for 48 Wks (Part I) | Number of Participants With an Early Virologic Response (EVR) That Achieved SVR | 32 Participants |
| Arm 2. PEG + RBV + BOC for 28 Wks (Part I) | Number of Participants With an Early Virologic Response (EVR) That Achieved SVR | 58 Participants |
| Arm 3. PEG + RBV + BOC (From Wk 4) for 24 Wks (Part I) | Number of Participants With an Early Virologic Response (EVR) That Achieved SVR | 58 Participants |
| Arm 4. PEG +RBV + BOC for 48 Wks (Part I) | Number of Participants With an Early Virologic Response (EVR) That Achieved SVR | 68 Participants |
| Arm 5. PEG + RBV+ BOC (From Wk 4) for 44 Wks (Part I) | Number of Participants With an Early Virologic Response (EVR) That Achieved SVR | 77 Participants |
| Arm 6. PEG + RBV + BOC for 48 Wks (Part II) | Number of Participants With an Early Virologic Response (EVR) That Achieved SVR | 8 Participants |
| Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II) | Number of Participants With an Early Virologic Response (EVR) That Achieved SVR | 21 Participants |
Secondary
Number of Participants With a Virologic Response at 72 Weeks Post Randomization That Achieved SVR
Participants with undetectable HCV-RNA at 72 weeks post randomization that achieved SVR (have undetectable HCV-RNA at FW 24 up to EOF) are reported. Participants missing data at FW 24 were considered to achieve SVR if 1. he/she had undetectable HCV-RNA at FW 12 or later 2. if he/she returned later to the study center and had undetectable HCV-RNA. HCV-RNA in plasma samples was detected an the RT-PCR assay. The lower limit of detection (LLD) was 29 IU/mL.
Time frame: At FW 24 up to EOF and at 72 weeks post randomization
Population: Participants who achieved SVR.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 1. PEG +RBV for 48 Wks (Part I) | Number of Participants With a Virologic Response at 72 Weeks Post Randomization That Achieved SVR | Missing HCV-RNA at 72 weeks post randomization | 1 Participants |
| Arm 1. PEG +RBV for 48 Wks (Part I) | Number of Participants With a Virologic Response at 72 Weeks Post Randomization That Achieved SVR | HCV-RNA positive at FW 24 | 0 Participants |
| Arm 1. PEG +RBV for 48 Wks (Part I) | Number of Participants With a Virologic Response at 72 Weeks Post Randomization That Achieved SVR | HCV-RNA negative at 72 weeks post randomization | 38 Participants |
| Arm 2. PEG + RBV + BOC for 28 Wks (Part I) | Number of Participants With a Virologic Response at 72 Weeks Post Randomization That Achieved SVR | HCV-RNA positive at FW 24 | 0 Participants |
| Arm 2. PEG + RBV + BOC for 28 Wks (Part I) | Number of Participants With a Virologic Response at 72 Weeks Post Randomization That Achieved SVR | HCV-RNA negative at 72 weeks post randomization | 53 Participants |
| Arm 2. PEG + RBV + BOC for 28 Wks (Part I) | Number of Participants With a Virologic Response at 72 Weeks Post Randomization That Achieved SVR | Missing HCV-RNA at 72 weeks post randomization | 5 Participants |
| Arm 3. PEG + RBV + BOC (From Wk 4) for 24 Wks (Part I) | Number of Participants With a Virologic Response at 72 Weeks Post Randomization That Achieved SVR | Missing HCV-RNA at 72 weeks post randomization | 2 Participants |
| Arm 3. PEG + RBV + BOC (From Wk 4) for 24 Wks (Part I) | Number of Participants With a Virologic Response at 72 Weeks Post Randomization That Achieved SVR | HCV-RNA negative at 72 weeks post randomization | 56 Participants |
| Arm 3. PEG + RBV + BOC (From Wk 4) for 24 Wks (Part I) | Number of Participants With a Virologic Response at 72 Weeks Post Randomization That Achieved SVR | HCV-RNA positive at FW 24 | 0 Participants |
| Arm 4. PEG +RBV + BOC for 48 Wks (Part I) | Number of Participants With a Virologic Response at 72 Weeks Post Randomization That Achieved SVR | HCV-RNA positive at FW 24 | 0 Participants |
| Arm 4. PEG +RBV + BOC for 48 Wks (Part I) | Number of Participants With a Virologic Response at 72 Weeks Post Randomization That Achieved SVR | HCV-RNA negative at 72 weeks post randomization | 67 Participants |
| Arm 4. PEG +RBV + BOC for 48 Wks (Part I) | Number of Participants With a Virologic Response at 72 Weeks Post Randomization That Achieved SVR | Missing HCV-RNA at 72 weeks post randomization | 2 Participants |
| Arm 5. PEG + RBV+ BOC (From Wk 4) for 44 Wks (Part I) | Number of Participants With a Virologic Response at 72 Weeks Post Randomization That Achieved SVR | HCV-RNA positive at FW 24 | 0 Participants |
| Arm 5. PEG + RBV+ BOC (From Wk 4) for 44 Wks (Part I) | Number of Participants With a Virologic Response at 72 Weeks Post Randomization That Achieved SVR | HCV-RNA negative at 72 weeks post randomization | 76 Participants |
| Arm 5. PEG + RBV+ BOC (From Wk 4) for 44 Wks (Part I) | Number of Participants With a Virologic Response at 72 Weeks Post Randomization That Achieved SVR | Missing HCV-RNA at 72 weeks post randomization | 1 Participants |
| Arm 6. PEG + RBV + BOC for 48 Wks (Part II) | Number of Participants With a Virologic Response at 72 Weeks Post Randomization That Achieved SVR | HCV-RNA negative at 72 weeks post randomization | 8 Participants |
| Arm 6. PEG + RBV + BOC for 48 Wks (Part II) | Number of Participants With a Virologic Response at 72 Weeks Post Randomization That Achieved SVR | Missing HCV-RNA at 72 weeks post randomization | 0 Participants |
| Arm 6. PEG + RBV + BOC for 48 Wks (Part II) | Number of Participants With a Virologic Response at 72 Weeks Post Randomization That Achieved SVR | HCV-RNA positive at FW 24 | 0 Participants |
| Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II) | Number of Participants With a Virologic Response at 72 Weeks Post Randomization That Achieved SVR | Missing HCV-RNA at 72 weeks post randomization | 1 Participants |
| Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II) | Number of Participants With a Virologic Response at 72 Weeks Post Randomization That Achieved SVR | HCV-RNA positive at FW 24 | 0 Participants |
| Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II) | Number of Participants With a Virologic Response at 72 Weeks Post Randomization That Achieved SVR | HCV-RNA negative at 72 weeks post randomization | 20 Participants |
Secondary
Number of Participants With a Virologic Response at Follow-up Week 12 That Achieved SVR
Treatment-naïve adults with CHC genotype 1 were assigned study medication. Participants with undetectable HCV-RNA at FW 12 that achieved SVR (have undetectable HCV-RNA at FW 24 (up to EOF) are reported. Participants missing data at FW 24 were considered to achieve SVR if 1. he/she had undetectable HCV-RNA at FW 12 or later 2. if he/she returned later to the study center and had undetectable HCV-RNA. HCV-RNA in plasma samples was detected with an RT-PCR assay. The LLD for the assay was 29 IU/mL.
Time frame: At FW 12 and FW 24 up to EOF
Population: Participants with undetectable HCV-RNA at FW 12.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 1. PEG +RBV for 48 Wks (Part I) | Number of Participants With a Virologic Response at Follow-up Week 12 That Achieved SVR | HCV-RNA negative at EOF | 39 Participants |
| Arm 1. PEG +RBV for 48 Wks (Part I) | Number of Participants With a Virologic Response at Follow-up Week 12 That Achieved SVR | Missing HCV-RNA at EOF | 0 Participants |
| Arm 1. PEG +RBV for 48 Wks (Part I) | Number of Participants With a Virologic Response at Follow-up Week 12 That Achieved SVR | HCV-RNA positive at EOF | 0 Participants |
| Arm 2. PEG + RBV + BOC for 28 Wks (Part I) | Number of Participants With a Virologic Response at Follow-up Week 12 That Achieved SVR | Missing HCV-RNA at EOF | 0 Participants |
| Arm 2. PEG + RBV + BOC for 28 Wks (Part I) | Number of Participants With a Virologic Response at Follow-up Week 12 That Achieved SVR | HCV-RNA negative at EOF | 58 Participants |
| Arm 2. PEG + RBV + BOC for 28 Wks (Part I) | Number of Participants With a Virologic Response at Follow-up Week 12 That Achieved SVR | HCV-RNA positive at EOF | 2 Participants |
| Arm 3. PEG + RBV + BOC (From Wk 4) for 24 Wks (Part I) | Number of Participants With a Virologic Response at Follow-up Week 12 That Achieved SVR | Missing HCV-RNA at EOF | 0 Participants |
| Arm 3. PEG + RBV + BOC (From Wk 4) for 24 Wks (Part I) | Number of Participants With a Virologic Response at Follow-up Week 12 That Achieved SVR | HCV-RNA negative at EOF | 58 Participants |
| Arm 3. PEG + RBV + BOC (From Wk 4) for 24 Wks (Part I) | Number of Participants With a Virologic Response at Follow-up Week 12 That Achieved SVR | HCV-RNA positive at EOF | 1 Participants |
| Arm 4. PEG +RBV + BOC for 48 Wks (Part I) | Number of Participants With a Virologic Response at Follow-up Week 12 That Achieved SVR | Missing HCV-RNA at EOF | 0 Participants |
| Arm 4. PEG +RBV + BOC for 48 Wks (Part I) | Number of Participants With a Virologic Response at Follow-up Week 12 That Achieved SVR | HCV-RNA negative at EOF | 69 Participants |
| Arm 4. PEG +RBV + BOC for 48 Wks (Part I) | Number of Participants With a Virologic Response at Follow-up Week 12 That Achieved SVR | HCV-RNA positive at EOF | 0 Participants |
| Arm 5. PEG + RBV+ BOC (From Wk 4) for 44 Wks (Part I) | Number of Participants With a Virologic Response at Follow-up Week 12 That Achieved SVR | Missing HCV-RNA at EOF | 0 Participants |
| Arm 5. PEG + RBV+ BOC (From Wk 4) for 44 Wks (Part I) | Number of Participants With a Virologic Response at Follow-up Week 12 That Achieved SVR | HCV-RNA negative at EOF | 76 Participants |
| Arm 5. PEG + RBV+ BOC (From Wk 4) for 44 Wks (Part I) | Number of Participants With a Virologic Response at Follow-up Week 12 That Achieved SVR | HCV-RNA positive at EOF | 0 Participants |
| Arm 6. PEG + RBV + BOC for 48 Wks (Part II) | Number of Participants With a Virologic Response at Follow-up Week 12 That Achieved SVR | HCV-RNA negative at EOF | 8 Participants |
| Arm 6. PEG + RBV + BOC for 48 Wks (Part II) | Number of Participants With a Virologic Response at Follow-up Week 12 That Achieved SVR | HCV-RNA positive at EOF | 0 Participants |
| Arm 6. PEG + RBV + BOC for 48 Wks (Part II) | Number of Participants With a Virologic Response at Follow-up Week 12 That Achieved SVR | Missing HCV-RNA at EOF | 0 Participants |
| Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II) | Number of Participants With a Virologic Response at Follow-up Week 12 That Achieved SVR | HCV-RNA positive at EOF | 1 Participants |
| Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II) | Number of Participants With a Virologic Response at Follow-up Week 12 That Achieved SVR | Missing HCV-RNA at EOF | 0 Participants |
| Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II) | Number of Participants With a Virologic Response at Follow-up Week 12 That Achieved SVR | HCV-RNA negative at EOF | 20 Participants |
Secondary
Number of Participants With SVR Based on a 4-week lead-in Treatment With PegIntron and Ribavirin
Number of participants with SVR (undetectable plasma HCV-RNA at FW 24 up to EOF). To assess the effect of lead-in treatment on SVR, participants with (Arm 3 and Arm 5) or without (Arm 2 and Arm 4) lead-in were pooled. Participants missing data at FW 24 were considered to achieve SVR if 1. he/she had undetectable HCV-RNA at FW 12 or later 2. he/she returned later to the study center and had undetectable HCV-RNA. HCV-RNA in plasma samples was detected with an RT-PCR assay. The LLD for the assay was 29 IU/mL.
Time frame: From FW 24 up to EOF
Population: Intent-to-Treat (ITT) population: All randomized participants who received at least one dose of any study medication (PegIntron, ribavirin, or boceprevir).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1. PEG +RBV for 48 Wks (Part I) | Number of Participants With SVR Based on a 4-week lead-in Treatment With PegIntron and Ribavirin | 135 Participants |
| Arm 2. PEG + RBV + BOC for 28 Wks (Part I) | Number of Participants With SVR Based on a 4-week lead-in Treatment With PegIntron and Ribavirin | 127 Participants |
p-value: 0.286495% CI: [-4.2, 14.3]Cochran-Mantel-Haenszel Chi-Square Test
Secondary
Number of Participants With SVR Based on Duration of Boceprevir Treatment
Number of participants with SVR (undetectable plasma HCV-RNA at FW 24 up to EOF). Participants from treatment arms receiving boceprevir for 28-weeks (Arm 2 and Arm 3) were pooled, and those receiving boceprevir for 48-weeks (Arm 4 and Arm 5) were pooled for the analysis. Participants missing data at FW 24 were considered to achieve SVR if 1. he/she had undetectable HCV-RNA at FW 12 or later 2. he/she returned later to the study center and had undetectable HCV-RNA. HCV-RNA in plasma samples was detected with an RT-PCR assay. The LLD for the assay was 29 IU/mL.
Time frame: From FW 24 up to EOF
Population: Intent-to-Treat (ITT) population: All randomized participants who received at least one dose of any study medication (PegIntron, ribavirin, or boceprevir).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1. PEG +RBV for 48 Wks (Part I) | Number of Participants With SVR Based on Duration of Boceprevir Treatment | 146 Participants |
| Arm 2. PEG + RBV + BOC for 28 Wks (Part I) | Number of Participants With SVR Based on Duration of Boceprevir Treatment | 116 Participants |
p-value: 0.000995% CI: [6.5, 24.8]Cochran-Mantel-Haenszel Chi-Square Test