Safety and Efficacy of Vaniprevir (MK7009) Administered With Pegylated-Interferon and Ribavirin (MK-7009-007)

Study Overview
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Brief Summary
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A study to evaluate how effective different levels of Vaniprevir (MK-7009), when administered with Pegylated-Interferon (Peg-IFN) and Ribavirin, are at achieving rapid viral response (RVR) i.e., undetectable hepatitis C virus [HCV] viral ribonucleic acid [RNA] at Week 4 in participants with chronic HCV infection. The primary hypothesis was that the proportion of participants in one or more of the Vaniprevir treatment groups achieving RVR would be greater than the proportion of placebo participants achieving RVR when Vaniprevir and placebo were co-administered with Peg-IFN/Ribavirin.

Official Title
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A Phase II, Randomized, Placebo-Controlled Study to Evaluate the Safety and Efficacy of MK7009 Administered Concomitantly With Pegylated-Interferon and Ribavirin for 28 Days in Treatment-Naive Patients With Chronic Hepatitis C Infection

Conditions
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Hepatitis C

Intervention / Treatment
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* Drug: Comparator: Vaniprevir
* Drug: Comparator: Pegylated-Interferon (Peg-IFN)
* Drug: Comparator: Ribavirin
* Drug: Comparator: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient has chronic Genotype 1 Hepatitis C infection Exclusion Criteria: Subject has been previously treated for HCV Has Human Immunodeficiency Virus (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: 18 Years
Maximum Age: 65 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 |
| --- | --- |
| Placebo Comparator: Placebo + Peg-IFN/Ribavirin<br>Participants took double-blind Placebo + Peg-IFN/Ribavirin from Week 1 to Week 4, followed by open-label Peg-IFN/Ribavirin from Week 5 to Week 48. | Drug: Comparator: Pegylated-Interferon (Peg-IFN)<br>* Peg-IFN 180 mcg once-weekly subcutaneous injection; duration of treatment: 48 weeks<br>Drug: Comparator: Ribavirin<br>* Ribavirin 200 mg tablet b.i.d. (dose based on body weight); duration of treatment: 48 weeks<br>|
| Experimental: Vaniprevir 300 mg b.i.d. + Peg-IFN/Ribavirin<br>Participants took double-blind Vaniprevir 300 mg twice daily (b.i.d.) + Peg-IFN/Ribavirin from Week 1 to Week 4, followed by open-label Peg-IFN/Ribavirin from Week 5 to Week 48. | Drug: Comparator: Vaniprevir<br>* Vaniprevir 300 mg b.i.d., 600 mg b.i.d., 600 mg q.d., or 800 mg q.d.; duration of treatment: 28 days<br>* Other names: MK-7009;Drug: Comparator: Pegylated-Interferon (Peg-IFN)<br>* Peg-IFN 180 mcg once-weekly subcutaneous injection; duration of treatment: 48 weeks<br>Drug: Comparator: Ribavirin<br>* Ribavirin 200 mg tablet b.i.d. (dose based on body weight); duration of treatment: 48 weeks<br>|
| Experimental: Vaniprevir 600 mg b.i.d. + Peg-IFN/Ribavirin<br>Participants took double-blind Vaniprevir 600 mg b.i.d. + Peg-IFN/Ribavirin from Week 1 to Week 4, followed by open-label Peg-IFN/Ribavirin from Week 5 to Week 48. | Drug: Comparator: Vaniprevir<br>* Vaniprevir 300 mg b.i.d., 600 mg b.i.d., 600 mg q.d., or 800 mg q.d.; duration of treatment: 28 days<br>* Other names: MK-7009;Drug: Comparator: Pegylated-Interferon (Peg-IFN)<br>* Peg-IFN 180 mcg once-weekly subcutaneous injection; duration of treatment: 48 weeks<br>Drug: Comparator: Ribavirin<br>* Ribavirin 200 mg tablet b.i.d. (dose based on body weight); duration of treatment: 48 weeks<br>|
| Experimental: Vaniprevir 600 mg q.d. + Peg-IFN/Ribavirin<br>Participants took double-blind Vaniprevir 600 mg q.d. + Peg-IFN/Ribavirin from Week 1 to Week 4, followed by open-label Peg-IFN/Ribavirin from Week 5 to Week 48. | Drug: Comparator: Vaniprevir<br>* Vaniprevir 300 mg b.i.d., 600 mg b.i.d., 600 mg q.d., or 800 mg q.d.; duration of treatment: 28 days<br>* Other names: MK-7009;Drug: Comparator: Pegylated-Interferon (Peg-IFN)<br>* Peg-IFN 180 mcg once-weekly subcutaneous injection; duration of treatment: 48 weeks<br>Drug: Comparator: Ribavirin<br>* Ribavirin 200 mg tablet b.i.d. (dose based on body weight); duration of treatment: 48 weeks<br>|
| Experimental: Vaniprevir 800 mg q.d. + Peg-IFN/Ribavirin<br>Participants took double-blind Vaniprevir 800 mg q.d. + Peg-IFN/Ribavirin from Week 1 to Week 4, followed by open-label Peg-IFN/Ribavirin from Week 5 to Week 48. | Drug: Comparator: Vaniprevir<br>* Vaniprevir 300 mg b.i.d., 600 mg b.i.d., 600 mg q.d., or 800 mg q.d.; duration of treatment: 28 days<br>* Other names: MK-7009;Drug: Comparator: Pegylated-Interferon (Peg-IFN)<br>* Peg-IFN 180 mcg once-weekly subcutaneous injection; duration of treatment: 48 weeks<br>Drug: Comparator: Ribavirin<br>* Ribavirin 200 mg tablet b.i.d. (dose based on body weight); duration of treatment: 48 weeks<br>Drug: Comparator: placebo<br>* Matching placebo to vaniprevir; duration of treatment: 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 RVR | Rapid Viral Response (RVR) was declared if Hepatitis C Virus (HCV) ribonucleic acid (RNA) was undetectable at Week 4. | Week 4 | 
| Number of Participants Experiencing an Adverse Event (AE) | The number of participants experiencing AEs in each treatment group was monitored during the Vaniprevir/Placebo treatment (Day 1 to Day 28) and safety follow-up (Day 29 to Day 42) periods. | Up to Day 42 | 
| Number of Participants Discontinuing From Study Therapy Due to AEs | 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 study therapy, whether or not considered related to the use of the product. | Day 1 to Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With ≥2-log10 Decrease in HCV RNA | The number of participants with at least a 2-log10 decrease from baseline in HCV RNA following 4 weeks of treatment with Placebo or Vaniprevir. | Baseline and Week 4 | 
| Number of Participants With ≥3-log10 Decrease in HCV RNA | The number of participants with at least a 3-log10 decrease from baseline in HCV RNA following 4 weeks of treatment with Placebo or Vaniprevir. | Baseline and Week 4 | 
| Mean Log Change From Baseline in HCV RNA | The mean changes from baseline in log10 HCV RNA in each vaniprevir group was compared against control treatment at Week 4. | Baseline and Week 4 |