Clinical trial NCT02133131: 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)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis C
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2014-05-07
Enrollment: 143
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants With Sustained Viral Response (SVR) 12 Weeks After Completing All Study Therapy (SVR12)
timeFrame: Up to 24 weeks
measure: Number of Participants Experiencing at Least 1 Adverse Event (AE)
timeFrame: Up to Week 14
measure: Number of Participants Discontinuing Study Therapy Due to an AE
timeFrame: Up to Week 12
Secondary outcomes:
measure: Percentage of Participants Achieving SVR 4 Weeks After Completing All Study Therapy (SVR4)
timeFrame: Up to 16 weeks
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Lawitz E, Poordad F, Gutierrez JA, Wells JT, Landaverde CE, Evans B, Howe A, Huang HC, Li JJ, Hwang P, Dutko FJ, Robertson M, Wahl J, Barr E, Haber B. Short-duration treatment with elbasvir/grazoprevir and sofosbuvir for hepatitis C: A randomized trial. Hepatology. 2017 Feb;65(2):439-450. doi: 10.1002/hep.28877. Epub 2016 Dec 19.