Grazoprevir (MK-5172) With Peg-Interferon and Ribavirin in Participants With Chronic Genotype 2 or 3 Hepatitis C (MK-5172-012)

Study Overview
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Brief Summary
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This study will evaluate the safety, tolerability, and antiviral activity of grazoprevir (MK-5172) when administered concomitantly with peg-interferon alfa-2b (Peg-IFN) and ribavirin (RBV) to treatment-naïve participants with chronic genotype 2 (GT2) or genotype 3 (GT3) hepatitis C virus (HCV) infections.

Official Title
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A Randomized, Partially Double-Blind, Active-Controlled, Dose-Ranging Estimation Study to Evaluate the Safety, Tolerability, and Efficacy of Different Regimens of MK-5172 When Administered Concomitantly With Pegylated-Interferon and Ribavirin in Treatment-Naive Patients With Chronic Genotype 2 or 3 Hepatitis C Virus Infection

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: Grazoprevir
* Drug: Placebo to Grazoprevir
* Drug: Peginterferon alfa-2b (Peg-IFN)
* Drug: Ribavirin (RBV)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body weight ≥ 88 lbs and ≤ 275 lbs Documented chronic Hepatitis C (CHC) GT2 or GT3 infection No known cirrhosis Agrees to use two acceptable methods of birth control during study and through 6 months after last dose of study drug Chest X-ray within the last 6 months Eye exam within the last 6 months Exclusion Criteria: Known to be human immunodeficiency virus (HIV) positive or co-infected with active hepatitis B virus (positive for Hepatitis B surface antigen) Prior approved or investigational treatment for hepatitis C Evidence of hepatocellular carcinoma Diabetic and/or high blood pressure with clinically significant eye exam findings Pre-existing psychiatric condition Clinical diagnosis of abuse of certain substances within specified timeframes Known medical condition that could interfere with participation Active or suspected cancer within the last 5 years Female who is pregnant, breastfeeding, or expecting to conceive or donate eggs Male who is planning to impregnate partner or donate sperm Male with a pregnant female partner Chronic hepatitis not caused by HCV

Ages Eligible for Study
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Minimum Age: 18 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: Grazoprevir 200 mg + Peg-IFN + RBV<br>Grazoprevir 200 mg in combination with Peg-IFN and RBV for 12 weeks. | Drug: Grazoprevir<br>* Grazoprevir 100 mg tablets once daily for 12 weeks.<br>* Other names: MK-5172;Drug: Peginterferon alfa-2b (Peg-IFN)<br>* Peg-IFN weekly subcutaneous injection at 1.5 mcg/kg/week for 12 or 24 weeks<br>* Other names: PegIntron®, SCH 054031;Drug: Ribavirin (RBV)<br>* Ribavirin 200 mg capsules twice daily at a dose of 600 mg to 1400 mg based on weight for 12 or 24 weeks<br>* Other names: Rebetol®, SCH 018908;|
| Experimental: Grazoprevir 400 mg + Peg-IFN + RBV<br>Grazoprevir 400 mg in combination with Peg-IFN and RBV for 12 weeks. | Drug: Grazoprevir<br>* Grazoprevir 100 mg tablets once daily for 12 weeks.<br>* Other names: MK-5172;Drug: Peginterferon alfa-2b (Peg-IFN)<br>* Peg-IFN weekly subcutaneous injection at 1.5 mcg/kg/week for 12 or 24 weeks<br>* Other names: PegIntron®, SCH 054031;Drug: Ribavirin (RBV)<br>* Ribavirin 200 mg capsules twice daily at a dose of 600 mg to 1400 mg based on weight for 12 or 24 weeks<br>* Other names: Rebetol®, SCH 018908;|
| Placebo Comparator: Placebo + Peg-IFN + RBV<br>Placebo to grazoprevir in combination with Peg-IFN and RBV for 12 weeks, followed by open-label Peg-IFN and RBV for an additional 12 weeks. | Drug: Placebo to Grazoprevir<br>* Placebo to Grazoprevir once daily for 12 weeks<br>Drug: Peginterferon alfa-2b (Peg-IFN)<br>* Peg-IFN weekly subcutaneous injection at 1.5 mcg/kg/week for 12 or 24 weeks<br>* Other names: PegIntron®, SCH 054031;Drug: Ribavirin (RBV)<br>* Ribavirin 200 mg capsules twice daily at a dose of 600 mg to 1400 mg based on weight for 12 or 24 weeks<br>* Other names: Rebetol®, SCH 018908;|
| Experimental: Grazoprevir 800 mg + Peg-IFN + RBV<br>Grazoprevir 800 mg in combination with Peg-IFN and RBV for 12 weeks. | Drug: Grazoprevir<br>* Grazoprevir 100 mg tablets once daily for 12 weeks.<br>* Other names: MK-5172;Drug: Peginterferon alfa-2b (Peg-IFN)<br>* Peg-IFN weekly subcutaneous injection at 1.5 mcg/kg/week for 12 or 24 weeks<br>* Other names: PegIntron®, SCH 054031;Drug: Ribavirin (RBV)<br>* Ribavirin 200 mg capsules twice daily at a dose of 600 mg to 1400 mg based on weight for 12 or 24 weeks<br>* Other names: Rebetol®, SCH 018908;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Achieving Complete Early Virologic Response (cEVR) in the Grazoprevir Treatment Arms | cEVR was defined as undetectable hepatitis C virus (HCV) ribonucleic acid (RNA) at Week 12. HCV RNA was measured using the Roche COBAS® Taqman® HCV Test, v.2.0 assay. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First Achievement of Undetectable HCV Ribonucleic Acid (RNA) | Time to first achievement of undetectable HCV RNA was determined by measuring HCV RNA at Treatment Days 1, 3, and 7; Treatment Weeks 2, 4, 8, 12, 16, 20, and 24; as well as Follow-up Weeks 4, 12, and 24. HCV RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay. | Baseline to Week 12 for Grazoprevir treatment arms, Week 24 for Placebo arm | 
| Number of Participants Achieving Rapid Viral Response (RVR) | RVR was defined as undetectable HCV RNA at Week 4. HCV RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay. | Week 4 | 
| Number of Participants Achieving Sustained Viral Response 12 Weeks After Completion of Therapy (SVR12) | SVR12 was defined as undetectable HCV RNA 12 weeks after completion of study therapy. HCV RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay. | Week 24 for Grazoprevir treatment arms, Week 36 for Placebo arm | 
| Number of Participants Achieving Sustained Viral Response 24 Weeks After Completion of Therapy (SVR24) | SVR24 was defined as undetectable HCV RNA 24 weeks after completion of study therapy. HCV RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay. | Week 36 for Grazoprevir treatment arms, Week 48 for Placebo arm | 
| Number of Participants Achieving Undetectable HCV RNA at Week 12 in the Placebo Arm | HCV RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay. | Week 12 | 
| Number of Participants Achieving Complete Early Virologic Response (cEVR) at Week 24 in the Placebo Arm | cEVR was defined as undetectable hepatitis C virus (HCV) ribonucleic acid (RNA) at Week 24 (i.e., after 12 weeks of placebo + 12 weeks of grazoprevir treatment). HCV RNA was measured using the Roche COBAS® Taqman® HCV Test, v2.0 assay. | Week 24 |