Efficacy and Safety of Grazoprevir (MK-5172), Elbasvir (MK-8742), and Sofosbuvir for Chronic Infection With Hepatitis C Virus Genotypes 1 and 3 (MK-5172-074)

Study Overview
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Brief Summary
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This is a study of grazoprevir (MK-5172) + elbasvir (MK-8742) and sofosbuvir (SOF) in treatment-naive participants with chronic hepatitis C (HCV) genotype (GT) 1 or GT3. The objective is to determine the proportion of participants achieving sustained virologic response 12 weeks after ending study treatment (SVR12).

Detailed Description
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The study is an open-label, single-center, multiple-arm investigation of a fixed-dose combination [FDC] of grazoprevir 100mg + elbasvir 50mg, and SOF 400mg, in treatment-naive participants with chronic HCV GT1 or GT3. The impact of study treatment regimens of varying duration on SVR12 (undetectable HCV ribonucleic acid [RNA] 12 weeks after ending study treatment) in cirrhotic (C) participants and non-cirrhotic (NC) participants will be determined (Part A). Any HCV GT1 participant from study Arms 1-4 in Part A who experienced virologic relapse will be offered retreatment consisting of 12 additional weeks of treatment with MK-5172/MK-8742 + SOF + ribavirin and 24 weeks of follow-up in Part B.

Official Title
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A Phase II Open-Label Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-5172, MK-8742, and Sofosbuvir in Treatment-Naïve Subjects With Chronic HCV GT1 or GT3 Infection

Conditions
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Hepatitis C

Intervention / Treatment
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* Drug: Grazoprevir/Elbasvir FDC
* Drug: Sofosbuvir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: has HCV RNA ≥10,000 IU/mL in peripheral blood at the time of screening has documented chronic HCV GT1 or GT3 infection has either negative or positive history of liver cirrhosis based on liver biopsy, Fibroscan, or FibroSure ® (Fibrotest®) is treatment naïve to all anti-HCV treatment Exclusion Criteria: has evidence of decompensated liver disease is coinfected with hepatitis B virus (e.g. hepatitis B surface antigen positive) or human immunodeficiency virus has a history of malignancy ≤5 years prior to signing informed consent, or is under evaluation for other active or suspected malignancy has cirrhosis and liver imaging within 6 months of Day 1 showing evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC has clinically-relevant drug or alcohol abuse within 12 months of screening has any of the following conditions: organ transplants other than cornea and hair, poor venous access that precludes routine peripheral blood sampling, history of gastric surgery or malabsorption disorders, or any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids during the course of the trial has a history of 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GT1:NC Grazoprevir/Elbasvir+SOF 4wk<br>Participants took grazoprevir/elbasvir (100mg/50mg) FDC with SOF 400mg once daily (q.d.) by mouth for 4 weeks (n=30 planned). | Drug: Grazoprevir/Elbasvir FDC<br>* FDC tablet containing grazoprevir 100 mg + elbasvir 50 mg taken q.d. by mouth.<br>* Other names: MK-5172A, Zepatier;Drug: Sofosbuvir<br>* Sofosbuvir 400mg tablet taken q.d. by mouth.<br>|
| Experimental: GT1:NC Grazoprevir/Elbasvir+SOF 6wk<br>Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 6 weeks (n=30 planned). | Drug: Grazoprevir/Elbasvir FDC<br>* FDC tablet containing grazoprevir 100 mg + elbasvir 50 mg taken q.d. by mouth.<br>* Other names: MK-5172A, Zepatier;Drug: Sofosbuvir<br>* Sofosbuvir 400mg tablet taken q.d. by mouth.<br>|
| Experimental: GT1:C Grazoprevir/Elbasvir+SOF 6wk<br>Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 6 weeks (n=20 planned). | Drug: Grazoprevir/Elbasvir FDC<br>* FDC tablet containing grazoprevir 100 mg + elbasvir 50 mg taken q.d. by mouth.<br>* Other names: MK-5172A, Zepatier;Drug: Sofosbuvir<br>* Sofosbuvir 400mg tablet taken q.d. by mouth.<br>|
| Experimental: GT1:C Grazoprevir/Elbasvir+SOF 8wk<br>Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 8 weeks (n=20 planned). | Drug: Grazoprevir/Elbasvir FDC<br>* FDC tablet containing grazoprevir 100 mg + elbasvir 50 mg taken q.d. by mouth.<br>* Other names: MK-5172A, Zepatier;Drug: Sofosbuvir<br>* Sofosbuvir 400mg tablet taken q.d. by mouth.<br>|
| Experimental: GT3:NC Grazoprevir/Elbasvir+SOF 8wk<br>Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 8 weeks (n=15 planned). | Drug: Grazoprevir/Elbasvir FDC<br>* FDC tablet containing grazoprevir 100 mg + elbasvir 50 mg taken q.d. by mouth.<br>* Other names: MK-5172A, Zepatier;Drug: Sofosbuvir<br>* Sofosbuvir 400mg tablet taken q.d. by mouth.<br>|
| Experimental: GT3:NC Grazoprevir/Elbasvir+SOF 12wk<br>Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 12 weeks (n=15 planned). | Drug: Grazoprevir/Elbasvir FDC<br>* FDC tablet containing grazoprevir 100 mg + elbasvir 50 mg taken q.d. by mouth.<br>* Other names: MK-5172A, Zepatier;Drug: Sofosbuvir<br>* Sofosbuvir 400mg tablet taken q.d. by mouth.<br>|
| Experimental: GT3:C Grazoprevir/Elbasvir+SOF 12wk<br>Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 12 weeks (n=10 planned). | Drug: Grazoprevir/Elbasvir FDC<br>* FDC tablet containing grazoprevir 100 mg + elbasvir 50 mg taken q.d. by mouth.<br>* Other names: MK-5172A, Zepatier;Drug: Sofosbuvir<br>* Sofosbuvir 400mg tablet taken q.d. by mouth.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Viral Response (SVR) 12 Weeks After Completing All Study Therapy (SVR12) | The percentage of participants achieving SVR12, defined as HCV ribonucleic acid (RNA) <15 IU/mL 12 weeks after completing all study therapy, was determined for each arm. Plasma levels of HCV RNA were measured using the Roche COBAS© AmpliPrep/COBAS© TaqMan© HCV Test v. 2.0. | Up to 24 weeks | 
| Number of Participants Experiencing at Least 1 Adverse Event (AE) | An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. | Up to Week 14 | 
| Number of Participants Discontinuing Study Therapy Due to an AE | An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. | Up to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving SVR 4 Weeks After Completing All Study Therapy (SVR4) | The percentage of participants achieving SVR4, defined as HCV ribonucleic acid (RNA) <15 IU/mL 4 weeks after completing all study therapy, was determined for each arm. Plasma levels of HCV RNA were measured using the Roche COBAS© AmpliPrep/COBAS© TaqMan© HCV Test v. 2.0. | Up to 16 weeks |