Safety and Efficacy of Vaniprevir (MK-7009) With Pegylated Interferon (Peg-IFN) and Ribavirin (RBV) in Treatment-Experienced Hepatitis C Virus (HCV) Participants (MK-7009-009)

Study Overview
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Brief Summary
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The purpose of this study is to test the safety, tolerability, and efficacy of 4 regimens of Vaniprevir + Peg-IFN and Ribavirin as compared to Placebo (PBO) + Peg-IFN/RBV. The primary hypotheses are that Vaniprevir is well tolerated, and that Vaniprevir 600 mg twice daily (b.i.d.) is superior to the control regimen for the percentage of non-cirrhotic (NC) participants achieving undetectable HCV ribonucleic acid (RNA) 24 weeks after the end of study therapy (SVR24).

Official Title
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A Phase II Randomized, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Efficacy of 4 Different Regimens of MK-7009 When Administered Concomitantly With Pegylated Interferon and Ribavirin in Treatment-Experienced Patients With Chronic Genotype 1 Hepatitis C Virus Infection

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: Vaniprevir
* Drug: Pegylated Interferon (Peg-IFN)
* Drug: Ribavirin (RBV)
* Drug: Placebo (PBO)


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Has chronic HCV genotype 1 infection Is treatment-experienced For the non-cirrhotic population, has had a liver biopsy without evidence of cirrhosis and hepatocellular carcinoma; for the cirrhotic population, has had a liver biopsy with evidence of cirrhosis and without evidence of hepatocellular carcinoma. Exclusion criteria: Has not tolerated previous course peg-IFN and RBV Is unlikely to tolerate at least 24 weeks of continuous therapy with Peg-IFN and RBV Is co-infected with Human Immunodeficiency Virus (HIV) and/or hepatitis B Consumes excessive amounts of alcohol Has a history of drug or alcohol abuse If female, participant is pregnant or breastfeeding Has been in a clinical trail with an investigational drug in the last 30 days Has used IFN/Peg-IFN and RBV in the last 3 months

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 |
| --- | --- |
| Experimental: 24-wk Vaniprevir 600 mg + Peg-IFN/RBV<br>Vaniprevir 600 mg (total daily dose) and RBV (1000 mg or 1200 mg total daily dose based on body weight) twice daily (b.i.d.) and Peg-IFN 180 mcg injection once weekly for 24 weeks. | Drug: Vaniprevir<br>* Participants took capsules containing 100 mg Vaniprevir twice daily (b.i.d.), three in the morning (300 mg and 600 mg regimens) and three in the evening (600 mg regimen only), orally, for 24 or 48 weeks.<br>* Other names: MK-7009;Drug: Pegylated Interferon (Peg-IFN)<br>* Participants used prefilled syringe containing 180 µg/0.5 mL Peg-IFN, for weekly subcutaneous injection, for 24 or 48 weeks<br>* Other names: PEGASYS™;Drug: Ribavirin (RBV)<br>* Participants took tablets containing 200 mg RBV, 5 or 6 tablet dosage based on the participant's weight, with food, for 24 or 48 weeks. The dose was 1000 mg for participants weighing <=75 kg and 1200 mg for participants weighing >75 kg.<br>* Other names: COPEGUS™;|
| Experimental: 24-wk Vaniprevir 600 mg + 24-wk PBO + Peg-IFN/RBV<br>Vaniprevir 600 mg (total daily dose) and RBV (1000 mg or 1200 mg total daily dose based on body weight) b.i.d. and Peg-IFN 180 mcg injection once weekly for 24 weeks, followed by PBO and RBV (1000 mg or 1200 mg total daily dose based on body weight) b.i.d. and Peg-IFN 180 mcg injection once weekly for an additional 24 weeks. | Drug: Vaniprevir<br>* Participants took capsules containing 100 mg Vaniprevir twice daily (b.i.d.), three in the morning (300 mg and 600 mg regimens) and three in the evening (600 mg regimen only), orally, for 24 or 48 weeks.<br>* Other names: MK-7009;Drug: Pegylated Interferon (Peg-IFN)<br>* Participants used prefilled syringe containing 180 µg/0.5 mL Peg-IFN, for weekly subcutaneous injection, for 24 or 48 weeks<br>* Other names: PEGASYS™;Drug: Ribavirin (RBV)<br>* Participants took tablets containing 200 mg RBV, 5 or 6 tablet dosage based on the participant's weight, with food, for 24 or 48 weeks. The dose was 1000 mg for participants weighing <=75 kg and 1200 mg for participants weighing >75 kg.<br>* Other names: COPEGUS™;Drug: Placebo (PBO)<br>* Participants took PBO capsules matching Vaniprevir capsules, three in the morning and three in the evening, for 24 or 48 weeks.<br>|
| Experimental: 48-wk Vaniprevir 300 mg + Peg-IFN/RBV<br>Vaniprevir 300 mg (total daily dose, taken once daily [q.d.]) and RBV (1000 mg or 1200 mg total daily dose based on body weight) b.i.d. and Peg-IFN 180 mcg injection once weekly for 48 weeks. | Drug: Vaniprevir<br>* Participants took capsules containing 100 mg Vaniprevir twice daily (b.i.d.), three in the morning (300 mg and 600 mg regimens) and three in the evening (600 mg regimen only), orally, for 24 or 48 weeks.<br>* Other names: MK-7009;Drug: Pegylated Interferon (Peg-IFN)<br>* Participants used prefilled syringe containing 180 µg/0.5 mL Peg-IFN, for weekly subcutaneous injection, for 24 or 48 weeks<br>* Other names: PEGASYS™;Drug: Ribavirin (RBV)<br>* Participants took tablets containing 200 mg RBV, 5 or 6 tablet dosage based on the participant's weight, with food, for 24 or 48 weeks. The dose was 1000 mg for participants weighing <=75 kg and 1200 mg for participants weighing >75 kg.<br>* Other names: COPEGUS™;|
| Experimental: 48-wk Vaniprevir 600 mg + Peg-IFN/RBV<br>Vaniprevir 600 mg and RBV (1000 mg or 1200 mg based on body weight) b.i.d. and Peg-IFN 180 mcg injection once weekly for 48 weeks. | Drug: Vaniprevir<br>* Participants took capsules containing 100 mg Vaniprevir twice daily (b.i.d.), three in the morning (300 mg and 600 mg regimens) and three in the evening (600 mg regimen only), orally, for 24 or 48 weeks.<br>* Other names: MK-7009;Drug: Pegylated Interferon (Peg-IFN)<br>* Participants used prefilled syringe containing 180 µg/0.5 mL Peg-IFN, for weekly subcutaneous injection, for 24 or 48 weeks<br>* Other names: PEGASYS™;Drug: Ribavirin (RBV)<br>* Participants took tablets containing 200 mg RBV, 5 or 6 tablet dosage based on the participant's weight, with food, for 24 or 48 weeks. The dose was 1000 mg for participants weighing <=75 kg and 1200 mg for participants weighing >75 kg.<br>* Other names: COPEGUS™;|
| Placebo Comparator: 48-wk PBO + Peg-IFN/RBV<br>PBO and RBV (1000 mg or 1200 mg based on body weight) b.i.d. and Peg-IFN 180 mcg injection once weekly for 48 weeks. | Drug: Pegylated Interferon (Peg-IFN)<br>* Participants used prefilled syringe containing 180 µg/0.5 mL Peg-IFN, for weekly subcutaneous injection, for 24 or 48 weeks<br>* Other names: PEGASYS™;Drug: Ribavirin (RBV)<br>* Participants took tablets containing 200 mg RBV, 5 or 6 tablet dosage based on the participant's weight, with food, for 24 or 48 weeks. The dose was 1000 mg for participants weighing <=75 kg and 1200 mg for participants weighing >75 kg.<br>* Other names: COPEGUS™;Drug: Placebo (PBO)<br>* Participants took PBO capsules matching Vaniprevir capsules, three in the morning and three in the evening, for 24 or 48 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving SVR24 Following Treatment With Vaniprevir 600 mg b.i.d. | The percentage of non-cirrhotic participants with undetectable Hepatits C virus (HCV) ribonucleic acid (RNA) 24 weeks after completing treatment was determined for each Vaniprevir 600 mg b.i.d. and control regimen. Results for Vaniprevir 300 mg are presented as a Secondary Outcome Measure. | Up to 72 weeks | 
| Number of Participants Experiencing an Adverse Event (AE) | The number of non-cirrhotic participants experiencing AEs during the active Vaniprevir/PBO treatment and 14-day follow-up periods was monitored for each treatment regimen. An AE was defined as any unfavorable and unintended change in the structure (signs), function (symptoms), or chemistry (laboratory data) of the body temporally associated with any use of a Sponsor product, whether or not considered related to the use of the product. | Up to 73 weeks | 
| Number of Participants Discontinuing From Study Treatment Due to AEs | The number of non-cirrhotic participants withdrawing from study treatment due to AEs during the active Vaniprevir/PBO treatment and 14-day follow-up periods was monitored for each treatment regimen. | Up to 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving SVR24 Following Treatment With Vaniprevir 300 mg b.i.d. | The percentage of non-cirrhotic participants treated with Vaniprevir 300 mg b.i.d. with undetectable HCV RNA 24 weeks after completing treatment was determined. | 72 weeks | 
| Percentage of Participants Achieving cEVR | The percentage of non-cirrhotic participants with complete early viral response (cEVR; undetectable HCV RNA at Week 12) was determined for each Vaniprevir dose. Since each of the Vaniprevir 600 mg arms had the same treatment history at this point in the study, the data were pooled for analysis. | Up to Week 60 | 
| Percentage of Participants Achieving SVR24 After 24 Weeks of Vaniprevir 600 mg b.i.d. | The percentage of participants achieving SVR24 after the 24-week Vaniprevir 600 mg b.i.d. regimen at Week 48 was compared to the control regimen. | Week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hepatitis C