Efficacy and Safety of Combination Grazoprevir (MK-5172)/Elbasvir (MK-8742) Versus Sofosbuvir + Pegylated Interferon + Ribavirin in Hepatitis C Virus Genotype 1, 4 or 6 Infection (MK-5172-077)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 3

Conditions: Hepatitis C

Treatments: Drug: Grazoprevir/Elbasvir (100 mg/50 mg) FDC; Drug: Sofosbuvir; Biological: PegIntron; Drug: Ribavirin

Study type: Interventional

Funder types: Industry

Identifiers

NCT02358044

5172-077

2014-003836-38 (EudraCT Number)

Details and patient eligibility

About

This is a study comparing grazoprevir (MK-5172) plus elbasvir (MK-8742) treatment with sofosbuvir (SOF) plus Pegylated Interferon plus Ribavirin (RBV) [PR] treatment in treatment-naïve and prior PR treatment failure participants with chronic Hepatitis C Virus (HCV) genotype (GT)1, GT4, or GT6 infection. The primary objectives are to compare efficacy (assessed by the percentage of participants achieving sustained virologic response 12 weeks after ending study treatment [SVR12]) and safety between the grazoprevir plus elbasvir treatment arm and the SOF plus PR treatment arm. The primary hypothesis is that the percentage of participants achieving SVR12 in the grazoprevir plus elbasvir treatment arm is non-inferior to that in the SOF plus PR treatment arm.

Enrollment: 257 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Weigh ≥40 kg and ≤125 kg
• documented chronic HCV GT1, GT4, or GT6 infection
• cirrhosis/absence of cirrhosis defined by liver biopsy, Fibroscan, or FibroSure®
• either treatment naïve or PR Null Responder, PR Partial Responder, or PR Prior Relapser
• participant and partner both agree to use at least use at least 2 effective methods of contraception from at least 2 weeks prior to Day 1 and continue until up to 6 months after last dose of study drug, or longer if dictated by local regulations

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
• 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 any of the following conditions: immunologically-mediated disease, 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, history of chronic hepatitis not caused by HCV

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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257 participants in 2 patient groups

Grazoprevir + Elbasvir

Experimental group

Description:

Participants receive a fixed-dose combination (FDC) tablet of 100 mg grazoprevir and 50 mg elbasvir for 12 weeks, followed by 24 weeks of follow-up.

Treatment:

Drug: Ribavirin

Biological: PegIntron

Drug: Sofosbuvir

SOF + PR

Active Comparator group

Description:

Participants receive SOF (400 mg) combined with PegIntron (1.5 mcg/kg) plus RBV (1000-1200 mg weight-based dose) for 12 weeks, followed by 24 weeks of follow-up.

Treatment:

Drug: Grazoprevir/Elbasvir (100 mg/50 mg) FDC