Hepatitis C
Conditions
Brief summary
The study evaluates safety and efficacy of vaniprevir (MK7009), when administered with Pegylated-Interferon (peg-IFN) and Ribavirin, in Japanese patients with Hepatitis C infection. The primary hypotheses are that 1.) the proportion of patients achieving rapid viral response (RVR) in one or more of the vaniprevir treatment groups is superior to that in the placebo group, when each is administered concomitantly with pegylated interferon (peg-IFN) α-2a and ribavirin; and 2.) vaniprevir at the studied doses is well tolerated compared with placebo, when each is administered concomitantly with peg-IFN α-2a and ribavirin for 28 days.
Interventions
DRUGVaniprevir
Vaniprevir oral capsule administered twice daily (200, 600 or 1200 mg/day) for 28 days
Open-label peg-IFN alfa-2a subcutaneous injection (sourced locally) administered weekly, 180 micrograms, for 6 weeks
DRUGRibavirin
Open-label ribavirin (sourced locally) administered orally twice daily, 600 to 1000 mg/day, for 6 weeks
DRUGComparator: Placebo
Placebo to vaniprevir oral capsule twice daily for 28 days
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 64 Years
Healthy volunteers
No
Inclusion criteria
* Has chronic genotype 1 Hepatitis C infection
Exclusion criteria
* Has not tolerated previous course of peg-IFN and ribavirin * Has HIV * Has Hepatitis B * Has a history of clinically significant medical condition that may interfere with the study (e.g., stroke or chronic seizures or major neurological disorder) or is contraindicated for treatment with peg-IFN and ribavirin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Rapid Viral Response | Week 4 | Rapid viral response (RVR) is defined as undetectable hepatitis C virus ribonucleic acid (HCV RNA) at Week 4. Serum HCV RNA levels were measured using Roche COBAS TaqMan HCV Auto assay. The limit of quantification was 1.2 log IU/mL (15 IU/mL) and the limit of detection was \<1.2 log IU/mL, but with no specific value. The Data-As-Observed (DAO) approach was used to handle missing data. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving a > or = 2-log10 Decrease in HCV RNA From Baseline to Week 4 | Baseline and Week 4 | Serum HCV RNA levels were measured using Roche COBAS TaqMan HCV Auto assay. The DAO approach was used to handle missing data. |
| Percentage of Participants Achieving a > or = 3-log10 Decrease in HCV RNA From Baseline to Week 4 | Baseline and Week 4 | Serum HCV RNA levels were measured using Roche COBAS TaqMan HCV Auto assay. The DAO approach was used to handle missing data. |
| Change From Baseline in HCV RNA in log10 at Week 4 | Baseline and Week 4 | Change from baseline in HCV RNA at Week 4 was calculated by subtracting Week 4 HCV RNA level from Baseline HCV RNA level. HCV RNA is measured as International Units per milliliter (IU/mL). Serum HCV RNA levels were measured using Roche COBAS TaqMan HCV Auto assay. The DAO approach was used to handle missing data. |
| Number of Participants Who Experienced at Least One Adverse Event | Up to 6 weeks | An adverse event is any unfavorable and unintended change in the structure, function, or chemistry of the body whether or not considered related to the study treatment. |
| Number of Participants Who Discontinued Study Drug Due to an Adverse Event | Up to 6 weeks | An adverse event is any unfavorable and unintended change in the structure, function, or chemistry of the body whether or not considered related to the study treatment. |
Participant flow
Pre-assignment details
Initial treatment period (Part 1) includes up through Week 6; Extension period (Part 2) includes from Week 6 through Week 96.
Participants by arm
| Arm | Count |
|---|---|
| Vaniprevir 200 mg + Peg-IFN + Ribavirin Participants received vaniprevir 100 mg twice daily in combination with peg-IFN and ribavirin for 28 days. Participants continued peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. | 23 |
| Vaniprevir 600 mg + Peg-IFN + Ribavirin Participants received vaniprevir 300 mg twice daily in combination with peg-IFN and ribavirin for 28 days. Participants continued peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. | 22 |
| Vaniprevir 1200 mg + Peg-IFN + Ribavirin Participants received vaniprevir 600 mg twice daily in combination with peg-IFN and ribavirin for 28 days. Participants continued peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. | 23 |
| Placebo + Peg-IFN + Ribavirin Participants received placebo twice daily in combination with peg-IFN and ribavirin for 28 days. Participants continued peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. | 22 |
| Total | 90 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Extension Period (Part 2) | Adverse Event | 0 | 0 | 1 | 1 |
| Extension Period (Part 2) | Lack of Efficacy | 0 | 0 | 0 | 1 |
| Extension Period (Part 2) | Physician Decision | 0 | 1 | 1 | 0 |
| Extension Period (Part 2) | Withdrawal by Subject | 0 | 2 | 1 | 1 |
Baseline characteristics
| Characteristic | Vaniprevir 200 mg + Peg-IFN + Ribavirin | Vaniprevir 600 mg + Peg-IFN + Ribavirin | Vaniprevir 1200 mg + Peg-IFN + Ribavirin | Placebo + Peg-IFN + Ribavirin | Total |
|---|---|---|---|---|---|
| Age, Continuous | 55.0 Years STANDARD_DEVIATION 6.5 | 54.3 Years STANDARD_DEVIATION 7.6 | 56.3 Years STANDARD_DEVIATION 7.8 | 54.7 Years STANDARD_DEVIATION 6.9 | 55.1 Years STANDARD_DEVIATION 7.1 |
| Genotype Genotype 1a | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 3 Participants |
| Genotype Genotype 1b | 22 Participants | 21 Participants | 23 Participants | 21 Participants | 87 Participants |
| Region of Enrollment Japan | 23 Participants | 22 Participants | 23 Participants | 22 Participants | 90 Participants |
| Sex: Female, Male Female | 12 Participants | 7 Participants | 12 Participants | 14 Participants | 45 Participants |
| Sex: Female, Male Male | 11 Participants | 15 Participants | 11 Participants | 8 Participants | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 23 / 23 | 22 / 22 | 23 / 23 | 22 / 22 |
| serious Total, serious adverse events | 2 / 23 | 2 / 22 | 0 / 23 | 2 / 22 |
Outcome results
Primary
Percentage of Participants Achieving Rapid Viral Response
Rapid viral response (RVR) is defined as undetectable hepatitis C virus ribonucleic acid (HCV RNA) at Week 4. Serum HCV RNA levels were measured using Roche COBAS TaqMan HCV Auto assay. The limit of quantification was 1.2 log IU/mL (15 IU/mL) and the limit of detection was \<1.2 log IU/mL, but with no specific value. The Data-As-Observed (DAO) approach was used to handle missing data.
Time frame: Week 4
Population: Per protocol population excludes participants for important deviations from the protocol that may substantially affect the results of the primary efficacy analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vaniprevir 200 mg + Peg-IFN + Ribavirin | Percentage of Participants Achieving Rapid Viral Response | 86.4 Percentage of participants |
| Vaniprevir 600 mg + Peg-IFN + Ribavirin | Percentage of Participants Achieving Rapid Viral Response | 95.0 Percentage of participants |
| Vaniprevir 1200 mg + Peg-IFN + Ribavirin | Percentage of Participants Achieving Rapid Viral Response | 76.2 Percentage of participants |
| Placebo + Peg-IFN + Ribavirin | Percentage of Participants Achieving Rapid Viral Response | 20.0 Percentage of participants |
p-value: <0.00195% CI: [37, 82.8]Miettinen and Nurminen
p-value: <0.00195% CI: [47.6, 89]Miettinen and Nurminen
p-value: <0.00195% CI: [24.9, 76]Miettinen and Nurminen
Secondary
Change From Baseline in HCV RNA in log10 at Week 4
Change from baseline in HCV RNA at Week 4 was calculated by subtracting Week 4 HCV RNA level from Baseline HCV RNA level. HCV RNA is measured as International Units per milliliter (IU/mL). Serum HCV RNA levels were measured using Roche COBAS TaqMan HCV Auto assay. The DAO approach was used to handle missing data.
Time frame: Baseline and Week 4
Population: Per protocol population excludes participants for important deviations from the protocol that may substantially affect the results of the primary efficacy analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vaniprevir 200 mg + Peg-IFN + Ribavirin | Change From Baseline in HCV RNA in log10 at Week 4 | Baseline | 6.6 IU/mL in Log10 | Standard Deviation 0.6 |
| Vaniprevir 200 mg + Peg-IFN + Ribavirin | Change From Baseline in HCV RNA in log10 at Week 4 | Change from Baseline | -6.5 IU/mL in Log10 | Standard Deviation 0.6 |
| Vaniprevir 600 mg + Peg-IFN + Ribavirin | Change From Baseline in HCV RNA in log10 at Week 4 | Baseline | 6.6 IU/mL in Log10 | Standard Deviation 0.6 |
| Vaniprevir 600 mg + Peg-IFN + Ribavirin | Change From Baseline in HCV RNA in log10 at Week 4 | Change from Baseline | -6.6 IU/mL in Log10 | Standard Deviation 0.6 |
| Vaniprevir 1200 mg + Peg-IFN + Ribavirin | Change From Baseline in HCV RNA in log10 at Week 4 | Change from Baseline | -6.3 IU/mL in Log10 | Standard Deviation 0.8 |
| Vaniprevir 1200 mg + Peg-IFN + Ribavirin | Change From Baseline in HCV RNA in log10 at Week 4 | Baseline | 6.6 IU/mL in Log10 | Standard Deviation 0.8 |
| Placebo + Peg-IFN + Ribavirin | Change From Baseline in HCV RNA in log10 at Week 4 | Change from Baseline | -4.7 IU/mL in Log10 | Standard Deviation 1.6 |
| Placebo + Peg-IFN + Ribavirin | Change From Baseline in HCV RNA in log10 at Week 4 | Baseline | 6.6 IU/mL in Log10 | Standard Deviation 0.5 |
95% CI: [-2.3, -1.2]
95% CI: [-2.4, -1.3]
95% CI: [-2.2, -1.1]
Secondary
Number of Participants Who Discontinued Study Drug Due to an Adverse Event
An adverse event is any unfavorable and unintended change in the structure, function, or chemistry of the body whether or not considered related to the study treatment.
Time frame: Up to 6 weeks
Population: The All Participants as Treated population consists of all randomized participants who received at least one dose of study treatment. Participants are included in the treatment group corresponding to the study treatment they actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vaniprevir 200 mg + Peg-IFN + Ribavirin | Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 0 Participants |
| Vaniprevir 600 mg + Peg-IFN + Ribavirin | Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 0 Participants |
| Vaniprevir 1200 mg + Peg-IFN + Ribavirin | Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 0 Participants |
| Placebo + Peg-IFN + Ribavirin | Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 0 Participants |
Secondary
Number of Participants Who Experienced at Least One Adverse Event
An adverse event is any unfavorable and unintended change in the structure, function, or chemistry of the body whether or not considered related to the study treatment.
Time frame: Up to 6 weeks
Population: The All Participants as Treated population consists of all randomized participants who received at least one dose of study treatment. Participants are included in the treatment group corresponding to the study treatment they actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vaniprevir 200 mg + Peg-IFN + Ribavirin | Number of Participants Who Experienced at Least One Adverse Event | 23 Participants |
| Vaniprevir 600 mg + Peg-IFN + Ribavirin | Number of Participants Who Experienced at Least One Adverse Event | 22 Participants |
| Vaniprevir 1200 mg + Peg-IFN + Ribavirin | Number of Participants Who Experienced at Least One Adverse Event | 23 Participants |
| Placebo + Peg-IFN + Ribavirin | Number of Participants Who Experienced at Least One Adverse Event | 22 Participants |
Secondary
Percentage of Participants Achieving a > or = 2-log10 Decrease in HCV RNA From Baseline to Week 4
Serum HCV RNA levels were measured using Roche COBAS TaqMan HCV Auto assay. The DAO approach was used to handle missing data.
Time frame: Baseline and Week 4
Population: Per protocol population excludes participants for important deviations from the protocol that may substantially affect the results of the primary efficacy analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vaniprevir 200 mg + Peg-IFN + Ribavirin | Percentage of Participants Achieving a > or = 2-log10 Decrease in HCV RNA From Baseline to Week 4 | 100 Percentage of participants |
| Vaniprevir 600 mg + Peg-IFN + Ribavirin | Percentage of Participants Achieving a > or = 2-log10 Decrease in HCV RNA From Baseline to Week 4 | 100 Percentage of participants |
| Vaniprevir 1200 mg + Peg-IFN + Ribavirin | Percentage of Participants Achieving a > or = 2-log10 Decrease in HCV RNA From Baseline to Week 4 | 100 Percentage of participants |
| Placebo + Peg-IFN + Ribavirin | Percentage of Participants Achieving a > or = 2-log10 Decrease in HCV RNA From Baseline to Week 4 | 95 Percentage of participants |
95% CI: [-11.3, 24.2]
95% CI: [-12.4, 24.2]
95% CI: [-12, 24.2]
Secondary
Percentage of Participants Achieving a > or = 3-log10 Decrease in HCV RNA From Baseline to Week 4
Serum HCV RNA levels were measured using Roche COBAS TaqMan HCV Auto assay. The DAO approach was used to handle missing data.
Time frame: Baseline and Week 4
Population: Per protocol population excludes participants for important deviations from the protocol that may substantially affect the results of the primary efficacy analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vaniprevir 200 mg + Peg-IFN + Ribavirin | Percentage of Participants Achieving a > or = 3-log10 Decrease in HCV RNA From Baseline to Week 4 | 100 Percentage of participants |
| Vaniprevir 600 mg + Peg-IFN + Ribavirin | Percentage of Participants Achieving a > or = 3-log10 Decrease in HCV RNA From Baseline to Week 4 | 100 Percentage of participants |
| Vaniprevir 1200 mg + Peg-IFN + Ribavirin | Percentage of Participants Achieving a > or = 3-log10 Decrease in HCV RNA From Baseline to Week 4 | 100 Percentage of participants |
| Placebo + Peg-IFN + Ribavirin | Percentage of Participants Achieving a > or = 3-log10 Decrease in HCV RNA From Baseline to Week 4 | 85 Percentage of participants |
95% CI: [-2.5, 36.2]
95% CI: [-3.4, 36.3]
95% CI: [-3.3, 36.1]