A Study of Safety and Efficacy of Vaniprevir Administered With Pegylated-Interferon and Ribavirin in Japanese Participants With Chronic Hepatitis C Infection (7009-016)

Study Overview
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Brief Summary
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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.

Official Title
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A Phase II Randomized Placebo-controlled Study to Evaluate the Safety and Efficacy of MK-7009 Administered Concomitantly With Pegylated-Interferon and Ribavirin for 28 Days in Japanese Treatment-Experienced Patients With Chronic Hepatitis C Infection

Conditions
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Hepatitis C

Intervention / Treatment
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* Drug: Vaniprevir
* Drug: Pegylated Interferon (peg-IFN)
* Drug: Ribavirin
* Drug: Comparator: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vaniprevir 200 mg + peg-IFN + ribavirin<br>Participants will receive vaniprevir 100 mg twice daily in combination with peg-IFN and ribavirin for 28 days. Participants will continue peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. | Drug: Vaniprevir<br>* Vaniprevir oral capsule administered twice daily (200, 600 or 1200 mg/day) for 28 days<br>* Other names: MK7009;Drug: Pegylated Interferon (peg-IFN)<br>* Open-label peg-IFN alfa-2a subcutaneous injection (sourced locally) administered weekly, 180 micrograms, for 6 weeks<br>Drug: Ribavirin<br>* Open-label ribavirin (sourced locally) administered orally twice daily, 600 to 1000 mg/day, for 6 weeks<br>|
| Experimental: Vaniprevir 600 mg + peg-IFN + ribavirin<br>Participants will receive vaniprevir 300 mg twice daily in combination with peg-IFN and ribavirin for 28 days. Participants will continue peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. | Drug: Vaniprevir<br>* Vaniprevir oral capsule administered twice daily (200, 600 or 1200 mg/day) for 28 days<br>* Other names: MK7009;Drug: Pegylated Interferon (peg-IFN)<br>* Open-label peg-IFN alfa-2a subcutaneous injection (sourced locally) administered weekly, 180 micrograms, for 6 weeks<br>Drug: Ribavirin<br>* Open-label ribavirin (sourced locally) administered orally twice daily, 600 to 1000 mg/day, for 6 weeks<br>|
| Experimental: Vaniprevir 1200 mg + peg-IFN + ribavirin<br>Participants will receive vaniprevir 600 mg twice daily in combination with peg-IFN and ribavirin for 28 days. Participants will continue peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. | Drug: Vaniprevir<br>* Vaniprevir oral capsule administered twice daily (200, 600 or 1200 mg/day) for 28 days<br>* Other names: MK7009;Drug: Pegylated Interferon (peg-IFN)<br>* Open-label peg-IFN alfa-2a subcutaneous injection (sourced locally) administered weekly, 180 micrograms, for 6 weeks<br>Drug: Ribavirin<br>* Open-label ribavirin (sourced locally) administered orally twice daily, 600 to 1000 mg/day, for 6 weeks<br>|
| Placebo Comparator: Placebo + peg-IFN + ribavirin<br>Participants will receive placebo twice daily in combination with peg-IFN and ribavirin for 28 days. Participants will continue peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. | Drug: Pegylated Interferon (peg-IFN)<br>* Open-label peg-IFN alfa-2a subcutaneous injection (sourced locally) administered weekly, 180 micrograms, for 6 weeks<br>Drug: Ribavirin<br>* Open-label ribavirin (sourced locally) administered orally twice daily, 600 to 1000 mg/day, for 6 weeks<br>Drug: Comparator: Placebo<br>* Placebo to vaniprevir oral capsule twice daily for 28 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline and Week 4 | 
| 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. | Baseline and Week 4 | 
| 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. | Baseline and Week 4 | 
| 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. | Up to 6 weeks | 
| 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. | Up to 6 weeks |