Vaniprevir Administered With Pegylated-interferon and Ribavirin in Japanese Treatment-Naïve Chronic Hepatitis C Participants (MK-7009-043)

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the safety, tolerability, and efficacy of vaniprevir given in combination with pegylated interferon alfa-2b (peg-IFN) and ribavirin (RBV) versus treatment with peg-IFN and RBV alone in Japanese treatment-naïve participants with chronic hepatitis C (CHC) genotype (GT)1. The primary efficacy hypothesis is that the percentage of participants achieving sustained virologic response 24 weeks after completion of all study therapy (SVR24) in at least one of the vaniprevir arms is superior to the percentage of participants achieving SVR24 in the control arm.

Official Title
-----------------
A Phase III Randomized, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Efficacy of MK-7009 When Administered Concomitantly With Peginterferon Alfa-2b and Ribavirin in Japanese Treatment-Naïve Patients With Chronic Hepatitis C Infection

Conditions
-----------------
Hepatitis C, Chronic

Intervention / Treatment
-----------------
* Drug: vaniprevir
* Drug: Placebo to vaniprevir
* Biological: Peg-IFN
* Drug: ribavirin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Japanese participant diagnosed with compensated CHC GT 1 Absence of ascites, bleeding esophageal varices, hepatic encephalopathy, or other signs or symptoms of advanced liver disease. IFN treatment naive No evidence of cirrhosis Exclusion criteria: Co-infection with human immunodeficiency virus (HIV) Positive hepatitis B surface antigen or other evidence of active hepatitis B infection Any other condition that is contraindicated or for which caution is required for treatment with peg-IFN or RBV Any condition or pre-study laboratory abnormality, or history of any illness, that, in the opinion of the investigator, might confound the results of the study or pose additional risk in administering the study drugs, peg-IFN and RBV, to the participant.

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vaniprevir 12 Week Arm<br>Participants on this arm receive 12 weeks of vaniprevir (300 mg twice daily) and then 12 weeks of placebo to vaniprevir along with 24 weeks of treatment with peg-IFN and RBV. | Drug: vaniprevir<br>* Capsules containing 150 mg vaniprevir, orally, two in the morning and two in the evening for 12 or 24 weeks<br>* Other names: MK-7009;Drug: Placebo to vaniprevir<br>* Placebo to vaniprevir, capsules, orally, twice daily for 12 weeks or 24 weeks<br>Biological: Peg-IFN<br>* Peg-IFN 1.5 μg/kg once per week, subcutaneously (SC) for 24 or 48 weeks<br>* Other names: PegIntron;Drug: ribavirin<br>* Capsules containing 200 mg RBV orally, 3 to 5 capsules, dosage based on the participant's weight (600 mg/day to 1000 mg/day), for 24 or 48 weeks<br>* Other names: REBETOL®;|
| Experimental: Vaniprevir 24 Week Arm<br>Participants on this arm receive 24 weeks of vaniprevir (300 mg twice daily) along with 24 weeks of treatment with peg-IFN and RBV. | Drug: vaniprevir<br>* Capsules containing 150 mg vaniprevir, orally, two in the morning and two in the evening for 12 or 24 weeks<br>* Other names: MK-7009;Biological: Peg-IFN<br>* Peg-IFN 1.5 μg/kg once per week, subcutaneously (SC) for 24 or 48 weeks<br>* Other names: PegIntron;Drug: ribavirin<br>* Capsules containing 200 mg RBV orally, 3 to 5 capsules, dosage based on the participant's weight (600 mg/day to 1000 mg/day), for 24 or 48 weeks<br>* Other names: REBETOL®;|
| Active Comparator: Control Arm<br>Participants on this arm receive 24 weeks of treatment with placebo to vaniprevir along with 48 weeks of treatment with peg-IFN and RBV. | Drug: Placebo to vaniprevir<br>* Placebo to vaniprevir, capsules, orally, twice daily for 12 weeks or 24 weeks<br>Biological: Peg-IFN<br>* Peg-IFN 1.5 μg/kg once per week, subcutaneously (SC) for 24 or 48 weeks<br>* Other names: PegIntron;Drug: ribavirin<br>* Capsules containing 200 mg RBV orally, 3 to 5 capsules, dosage based on the participant's weight (600 mg/day to 1000 mg/day), for 24 or 48 weeks<br>* Other names: REBETOL®;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Completion of All Study Therapy (SVR24) | SVR24 was defined as having an undetectable HCV RNA level 24 weeks after completion of all study therapy. | 24 weeks after 24 or 48 weeks of study therapy (up to 72 weeks) | 
| Percentage of Participants With One or More Tier 1 Adverse Events (AEs) During the Study | An adverse experience was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the product, was also an adverse experience. For this study, safety parameters or AEs of special interest that were identified a priori constituted Tier 1 safety endpoints that were subject to inferential testing for statistical significance. Tier 1 AEs on this study included serious rash, anemia (anemia plus haemoglobin decreased), neutropenia (neutropenia plus neutrophil count decreased), bilirubin increased and gastrointestinal adverse (GI) experiences (vomiting, nausea, and diarrhea). | From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 72 weeks) | 
| Percentage of Participants Who Discontinued Study Drug Due to an AE | An adverse experience was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the product, was also an adverse experience. | From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 72 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving SVR12 | SVR12 was defined as having an undetectable HCV RNA level 12 weeks after completion of all study therapy. | 12 weeks after 24 or 48 weeks of study therapy (up to 60 weeks) | 
| Percentage of Participants Achieving Rapid Virologic Response (RVR) | RVR was defined as having an undetectable HCV RNA level at Week 4. | At Week 4 | 
| Percentage of Participants Achieving Complete Early Virologic Response (cEVR) | cEVR was defined as having an undetectable HCV RNA level at Week 12. | At Week 12 | 
| Percentage of Participants Achieving Undetectable HCV RNA at the End of Treatment (EOT) | Participants were assessed for undetectable HCV RNA levels at the end of all study therapy. | At Week 24 or 48 | 
| Least Squares (LS) Mean Change From Baseline in HCV RNA (Log 10) | HCV RNA levels were assessed at baseline (BL) and during treatment weeks 2, 4, 8, 12, and 24 using the Roche TaqMan HCV assay, and transformed to Log 10 values. HCV RNA values below the limit of reliable quantification (LoQ) or the limit of detection (LoD) at any time point were handled as follows (imputations done for computational purposes): values below the LoQ but above the LoD were imputed with the LoQ minus 0.1; values below the LoD were imputed with the value of 0 Log IU/mL. HCV RNA levels below the LoD were considered undetectable. | Baseline, Week 2, Week 4, Week 8, Week 12, Week 24 |