Study of Vaniprevir Plus PegIntron®/Ribavirin in Japanese Participants With Chronic Hepatitis C Who Relapsed After Treatment (MK-7009-044)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, tolerability, and efficacy of vaniprevir given in combination with pegylated interferon alfa-2b (PegIntron®/peg-IFN) and ribavirin (RBV) in chronic hepatitis C (CHC) Genotype I (GT 1) participants who relapsed after previous therapy with interferon-based therapy. 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 300 mg twice daily treatment regimens is greater than 20% (historical data of standard of care treatment).

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

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: vaniprevir
* Biological: peg-IFN
* Drug: ribavirin


Participation Criteria
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Eligibility Criteria
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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 Has received and tolerated treatment with IFN-based therapy (IFN α, IFN β, or peg-IFN) with or without use of ribavirin, but failed to respond to the prior treatment (relapse or breakthrough) 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
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Minimum Age: 20 Years
Maximum Age: 70 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: None (Open Label)


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) along with 24 weeks of treatment with peg-IFN and RBV | Drug: vaniprevir<br>* vaniprevir 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 weeks<br>* Other names: PegIntron®;Drug: ribavirin<br>* Capsules containing 200 mg ribavirin, orally, 3 to 5 capsules, dosage based on participant weight (600 mg/day to 1000 mg/day), for 24 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>* vaniprevir 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 weeks<br>* Other names: PegIntron®;Drug: ribavirin<br>* Capsules containing 200 mg ribavirin, orally, 3 to 5 capsules, dosage based on participant weight (600 mg/day to 1000 mg/day), for 24 weeks<br>* Other names: REBETOL®;|

What is the study measuring?
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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. The percentage of participants achieving SVR24 were reported along with corresponding 95% Clopper-Pearson exact confidence intervals for each treatment regimen. | 24 weeks after 24 weeks of study therapy (up to 48 weeks) | 
| Percentage of Participants With One or More Specific Adverse Events (AEs) of Special Interest During the Study | An AE 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 AE. For this study, safety parameters or AEs of special interest that were identified a priori included serious rash, anemia (anemia plus haemoglobin decreased), neutropenia (neutropenia plus neutrophil count decreased), bilirubin increased and gastrointestinal (GI) adverse experiences (vomiting, nausea, and diarrhea). The percentage of participants with ≥1 specific AEs were reported along with corresponding 95% Clopper-Pearson exact confidence intervals for each treatment regimen. | From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks) | 
| Percentage of Participants Who Discontinued Study Drug Due to an AE | An AE 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 AE. | From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 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. The percentage of participants achieving SVR12 were reported along with corresponding 95% Clopper-Pearson exact confidence intervals for each treatment regimen. | 12 weeks after 24 weeks of study therapy (up to 36 weeks) | 
| Percentage of Participants Achieving Rapid Virologic Response (RVR) | RVR was defined as having an undetectable HCV RNA level at Week 4. The percentage of participants achieving RVR were reported along with corresponding 95% Clopper-Pearson exact confidence intervals for each treatment regimen. | 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. The percentage of participants achieving cEVR were reported along with corresponding 95% Clopper-Pearson exact confidence intervals for each treatment regimen. | 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. The percentage of participants with undetectable HCV RNA levels at EOT were reported along with corresponding 95% Clopper-Pearson exact confidence intervals for each treatment regimen. | At Week 24 | 
| 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 |