Elbasvir/Grazoprevir (EBR/GZR) and Sofosbuvir (SOF) With and Without Ribavirin (RBV) in Cirrhotic Subjects With Chronic Hepatitis C Virus (HCV) Genotype 3 (GT3) Infection (MK-5172-083)

Study Overview
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Brief Summary
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This is a randomized, multi-site, open-label trial of the co-administration of a fixed-dose combination (FDC) of EBR 50 mg + GZR (100 mg) (EBR/GZR) and SOF 400 mg, with and without RBV, in treatment-naïve (TN) and treatment-experienced (TE) participants with chronic HCV GT3 infection with compensated cirrhosis.

Official Title
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A Phase II, Randomized, Open-Label Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of Elbasvir/Grazoprevir (EBR/GZR) and Sofosbuvir (SOF) With and Without Ribavirin (RBV) in Cirrhotic Subjects With Chronic HCV GT3 Infection

Conditions
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Hepatitis C

Intervention / Treatment
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* Drug: Grazoprevir
* Drug: Elbasvir
* Drug: Ribavirin
* 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 screening has documented HCV GT3 (with no evidence of non-typeable or mixed GT infection) has compensated cirrhosis of the liver has liver imaging within 6 months of Day 1 with no evidence of hepatocellular carcinoma (HCC) is either HCV TN or TE (i.e., has documented prior virologic failure or intolerance to peg-interferon/ribavirin) is otherwise healthy as determined by medical history, physical examination, electrocardiogram (ECG), and clinical laboratory measurements has compensated cirrhosis of the liver is TN or TE (i.e., documented prior virologic failure or intolerance to peg-interferon/ribavirin) is not of reproductive potential, or agrees to not impregnate a partner or become pregnant for at least 2 weeks prior to the first dose of study drug, and for 7 months after the final dose of study drug (or longer if dictated by local regulations) Exclusion Criteria: has previously received one or more doses of a direct-acting antiviral (DAA) has evidence of decompensated liver disease is coinfected with hepatitis B (hepatitis B surface antigen [HBsAg] positive) has a recent (within 5 years) history of malignancy or is under evaluation for HCC or other suspected malignancy is currently or has participated (within past 30 days) in a study with an investigational compound has clinically-relevant drug or alcohol abuse within the past 12 months of screening is a female and is pregnant or breast-feeding is a male whose female partner is/are pregnant has any of the following: organ transplants poor venous access history of gastric surgery or malabsorption disorder current or history of clinically significant cardiac abnormalities or dysfunction chronic pulmonary disease hemoglobinopathy history of hospitalization within 3 months prior to enrollment medical or surgical condition that may result in need for hospitalization during the course of the study any condition requiring, or likely to require, chronic systemic administration of corticosteroids, tumor necrosis factor (TNF) antagonists, or other immunosuppresant drugs during the course of the study any condition, prestudy laboratory or ECG abnormality, or history of any illness, which could confound results of the study or pose additional risks in administering study drugs in the opinion of the investigator has a life-threatening serious AE (SAE) during the screening period has evidence of 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: Arm 1: HCV GT3 TN EBG/GZR+SOF+RBV 8 Weeks<br>TN HCV GT3 participants will take 1 fixed-dose combination (FDC) tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg once-daily (q.d.) with RBV (200 mg capsules; weight-based dosing) twice-daily (b.i.d.) for 8 weeks. | Drug: Grazoprevir<br>* GZR 100 mg is a component of the MK-5172A FDC tablet (also containing EBR 50 mg) and was taken q.d. by mouth in the morning.<br>* Other names: MK-5172;Drug: Elbasvir<br>* EBR 50 mg is a component of the MK-5172A FDC tablet (also containing GZR 100 mg) and was taken q.d. by mouth in the morning.<br>* Other names: MK-8742;Drug: Ribavirin<br>* RBV 200 mg capsules taken b.i.d. (morning and evening) by mouth at a total daily dose ranging from 800 mg to 1400 mg (total daily dose was based on participant body weight).<br>* Other names: Rebetol®;Drug: Sofosbuvir<br>* SOF 400 mg tablet taken q.d. by mouth in the morning with food.<br>* Other names: Sovaldi®, Harvoni®;|
| Experimental: Arm 2: HCV GT3 TN EBG/GZR+SOF 12 Weeks<br>TN HCV GT3 participants will take 1 FDC tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg q.d. for 12 weeks. | Drug: Grazoprevir<br>* GZR 100 mg is a component of the MK-5172A FDC tablet (also containing EBR 50 mg) and was taken q.d. by mouth in the morning.<br>* Other names: MK-5172;Drug: Elbasvir<br>* EBR 50 mg is a component of the MK-5172A FDC tablet (also containing GZR 100 mg) and was taken q.d. by mouth in the morning.<br>* Other names: MK-8742;Drug: Sofosbuvir<br>* SOF 400 mg tablet taken q.d. by mouth in the morning with food.<br>* Other names: Sovaldi®, Harvoni®;|
| Experimental: Arm 3: HCV GT3 TE EBG/GZR+SOF 12 Weeks<br>TE HCV GT3 participants will take 1 FDC tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg q.d. for 12 weeks. | Drug: Grazoprevir<br>* GZR 100 mg is a component of the MK-5172A FDC tablet (also containing EBR 50 mg) and was taken q.d. by mouth in the morning.<br>* Other names: MK-5172;Drug: Elbasvir<br>* EBR 50 mg is a component of the MK-5172A FDC tablet (also containing GZR 100 mg) and was taken q.d. by mouth in the morning.<br>* Other names: MK-8742;Drug: Sofosbuvir<br>* SOF 400 mg tablet taken q.d. by mouth in the morning with food.<br>* Other names: Sovaldi®, Harvoni®;|
| Experimental: Arm 4: HCV GT3 TE EBG/GZR+SOF+RBV 12 Weeks<br>TE HCV GT3 participants will take 1 FDC tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg q.d. with RBV (200 mg capsules; weight-based dosing) b.i.d. for 12 weeks. | Drug: Grazoprevir<br>* GZR 100 mg is a component of the MK-5172A FDC tablet (also containing EBR 50 mg) and was taken q.d. by mouth in the morning.<br>* Other names: MK-5172;Drug: Elbasvir<br>* EBR 50 mg is a component of the MK-5172A FDC tablet (also containing GZR 100 mg) and was taken q.d. by mouth in the morning.<br>* Other names: MK-8742;Drug: Ribavirin<br>* RBV 200 mg capsules taken b.i.d. (morning and evening) by mouth at a total daily dose ranging from 800 mg to 1400 mg (total daily dose was based on participant body weight).<br>* Other names: Rebetol®;Drug: Sofosbuvir<br>* SOF 400 mg tablet taken q.d. by mouth in the morning with food.<br>* Other names: Sovaldi®, Harvoni®;|
| Experimental: Arm 5: HCV GT3 TE EBG/GZR+SOF 16 Weeks<br>TE HCV GT3 participants will take 1 FDC tablet containing EBR 50 mg+GZR 100 mg and 1 tablet containing SOF 400 mg q.d. for 16 weeks. | Drug: Grazoprevir<br>* GZR 100 mg is a component of the MK-5172A FDC tablet (also containing EBR 50 mg) and was taken q.d. by mouth in the morning.<br>* Other names: MK-5172;Drug: Elbasvir<br>* EBR 50 mg is a component of the MK-5172A FDC tablet (also containing GZR 100 mg) and was taken q.d. by mouth in the morning.<br>* Other names: MK-8742;Drug: Sofosbuvir<br>* SOF 400 mg tablet taken q.d. by mouth in the morning with food.<br>* Other names: Sovaldi®, Harvoni®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving SVR12 (Sustained Virologic Response 12 Weeks After the End of All Study Therapy) | The percentage of participants achieving SVR12 (i.e., HCV ribnonucleic acid [RNA] < Lower Limit of Quantification [LLOQ] 12 weeks after completing study treatment) was determined. Plasma HCV RNA levels were determined with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay, which has a LLOQ of 15 IU/mL. | Up to Week 28 | 
| Percentage of Participants Experiencing an 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 18 weeks (up to 2 weeks after completion of study treatment) | 
| Percentage of Participants Discontinuing From 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 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving SVR24 (Sustained Virologic Response 24 Weeks After the End of All Study Therapy) | The percentage of participants achieving SVR24 (i.e., HCV RNA < LLOQ 24 weeks after completing study treatment) was determined. Plasma HCV RNA levels were determined with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay, which has a LLOQ of 15 IU/mL. | Up to Week 40 |