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)
- Registration Number
- NCT02133131
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 143
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description GT1:C Grazoprevir/Elbasvir+SOF 8wk Grazoprevir/Elbasvir FDC Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 8 weeks (n=20 planned). GT3:NC Grazoprevir/Elbasvir+SOF 8wk Grazoprevir/Elbasvir FDC Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 8 weeks (n=15 planned). GT3:C Grazoprevir/Elbasvir+SOF 12wk Grazoprevir/Elbasvir FDC Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 12 weeks (n=10 planned). GT3:NC Grazoprevir/Elbasvir+SOF 12wk Grazoprevir/Elbasvir FDC Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 12 weeks (n=15 planned). GT1:NC Grazoprevir/Elbasvir+SOF 4wk Grazoprevir/Elbasvir FDC Participants took grazoprevir/elbasvir (100mg/50mg) FDC with SOF 400mg once daily (q.d.) by mouth for 4 weeks (n=30 planned). GT1:NC Grazoprevir/Elbasvir+SOF 6wk Grazoprevir/Elbasvir FDC Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 6 weeks (n=30 planned). GT1:C Grazoprevir/Elbasvir+SOF 6wk Grazoprevir/Elbasvir FDC Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 6 weeks (n=20 planned). GT1:NC Grazoprevir/Elbasvir+SOF 4wk Sofosbuvir Participants took grazoprevir/elbasvir (100mg/50mg) FDC with SOF 400mg once daily (q.d.) by mouth for 4 weeks (n=30 planned). GT1:NC Grazoprevir/Elbasvir+SOF 6wk Sofosbuvir Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 6 weeks (n=30 planned). GT1:C Grazoprevir/Elbasvir+SOF 6wk Sofosbuvir Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 6 weeks (n=20 planned). GT1:C Grazoprevir/Elbasvir+SOF 8wk Sofosbuvir Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 8 weeks (n=20 planned). GT3:NC Grazoprevir/Elbasvir+SOF 8wk Sofosbuvir Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 8 weeks (n=15 planned). GT3:NC Grazoprevir/Elbasvir+SOF 12wk Sofosbuvir Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 12 weeks (n=15 planned). GT3:C Grazoprevir/Elbasvir+SOF 12wk Sofosbuvir Participants took grazoprevir/elbasvir (100mg/50mg) FDC + SOF 400mg q.d. by mouth for 12 weeks (n=10 planned).
- Primary Outcome Measures
Name Time Method Number of Participants Experiencing at Least 1 Adverse Event (AE) Up to Week 14 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.
Number of Participants Discontinuing Study Therapy Due to an AE Up to Week 12 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.
Percentage of Participants With Sustained Viral Response (SVR) 12 Weeks After Completing All Study Therapy (SVR12) Up to 24 weeks 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.
- Secondary Outcome Measures
Name Time Method Percentage of Participants Achieving SVR 4 Weeks After Completing All Study Therapy (SVR4) Up to 16 weeks 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.