Efficacy and Safety of Uprifosbuvir (MK-3682) + Ruzasvir (MK-8408) in Treating Hepatitis C Virus Infection Genotypes 1-6 (MK-3682-041)

Merck Sharp & Dohme (MSD)

Status and phase: Terminated; Phase 2

Conditions: Hepatitis C

Treatments: Drug: Ribavirin; Drug: Uprifosbuvir; Drug: Ruzasvir

Study type: Interventional

Funder types: Industry

Identifiers

NCT02956629

MK-3682-041 (Other Identifier)

3682-041

2016-003227-37 (EudraCT Number)

Details and patient eligibility

About

This is a nonrandomized, multi-site, open-label trial to evaluate a novel two-drug combination regimen (uprifosbuvir [MK-3682] 450 mg + ruzasvir [RZR; MK-8408] 180 mg once daily [q.d.] for 12 weeks) in male and female treatment-naïve (TN) or treatment-experienced (TE) participants with chronic hepatitis C virus (HCV) infection genotype (GT) GT1, GT2, GT3, GT4, GT5, or GT6 who have not previously received HCV direct-acting antiviral (DAA) therapy. Cirrhotic (C) and non-cirrhotic (NC) participants with and without human immunodeficiency virus (HIV) co-infection will be enrolled.

Full description

Any GT that meets virologic futility criteria will be given the option of extending treatment with uprifosbuvir + RZR to 16 weeks with ribavirin (RBV) added.

Enrollment: 282 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• has HCV ribonucleic acid (RNA) (≥10,000 IU/mL in peripheral blood) at the time of screening
• has documented chronic HCV GT1, GT2, GT3, GT4, GT5, or GT6 (with no evidence of non-typeable or mixed GT)
• is a female who is not of reproductive potential, or is a female of reproductive potential who agrees to avoid becoming pregnant from two weeks prior to Day 1 through 14 days after the last dose of study drug via abstinence or use of two approved contraceptives
• is C or NC
• if coinfected with HIV, has documented HIV infection prior to Day 1, and either does not use an antiretroviral therapy (ART) or has well-controlled HIV on stable ART (at least 4 weeks prior to study entry)

Exclusion criteria

• has evidence of decompensated liver disease
• is C and is Child-Pugh Class B or C, or has a Child-Tucotte-Pugh score >6
• is coinfected with hepatitis B virus (hepatitis B surface antigen or hepatitis B core antibody positive)
• is coinfected with HIV and has a recent (within 6 months prior to screening) opportunistic infection
• has a history of malignancy other than adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer or carcinoma in situ within 5 years of signing informed consent
• is C and has evidence (liver imaging within 6 months prior to Day 1) of hepatocellular carcinoma (HCC) or is under evaluation for HCC
• has participated in another investigational drug study within 30 days of signing informed consent
• is a female who is pregnant or breastfeeding or expecting to conceive or donate eggs from Day 1 through 6 months after the last dose of study drug or longer if dictated by local regulations, or is a male who is expecting to donate sperm from Day 1 through 14 days after the last dose of study drug or longer if dictated by local regulations, or is a male whose female partner(s) is/are pregnant or breastfeeding
• has clinically relevant alcohol or drug abuse within 12 months of screening
• has any of the following conditions: organ transplants other than cornea and hair; poor venous access; history of gastric surgery; clinically significant cardiac abnormality/dysfunction; any major medical condition which, in the opinion of the investigator, might interfere with participation; hospitalization within 3 months prior to enrollment; any condition that might require hospitalization; any condition requiring or likely to require chronic systemic administration of corticosteroids, tumor necrosis factor (TNF) antagonists, or immunosuppressant drugs; a life-threatening SAE during screening; or hepatitis not caused by HCV

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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282 participants in 6 patient groups

HCV GT1

Experimental group

Description:

Male and female participants with HCV GT1a or GT1b infection take uprifosbuvir 450 mg + RZR 180 mg for 12 weeks.

Treatment:

Drug: Ruzasvir

Drug: Uprifosbuvir

Drug: Ribavirin

HCV GT2

Experimental group

Description:

Male and female participants with HCV GT2 infection take uprifosbuvir 450 mg + RZR 180 mg for 12 weeks.

Treatment:

Drug: Ruzasvir

Drug: Uprifosbuvir

Drug: Ribavirin

HCV GT3

Experimental group

Description:

Male and female participants with HCV GT3 infection take uprifosbuvir 450 mg + RZR 180 mg for 12 weeks.

Treatment:

Drug: Ruzasvir

Drug: Uprifosbuvir

Drug: Ribavirin

HCV GT4

Experimental group

Description:

Male and female participants with HCV GT4 infection take uprifosbuvir 450 mg + RZR 180 mg for 12 weeks.

Treatment:

Drug: Ruzasvir

Drug: Uprifosbuvir

Drug: Ribavirin

HCV GT5

Experimental group

Description:

Male and female participants with HCV GT5 infection take uprifosbuvir 450 mg + RZR 180 mg for 12 weeks.

Treatment:

Drug: Ruzasvir

Drug: Uprifosbuvir

Drug: Ribavirin

HCV GT6

Experimental group

Description:

Male and female participants with HCV GT6 infection take uprifosbuvir 450 mg + RZR 180 mg for 12 weeks.

Treatment:

Drug: Ruzasvir

Drug: Uprifosbuvir

Drug: Ribavirin