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

NCT ID: NCT02956629

Last Updated: 2021-02-02

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 282 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-16
• Study Completion Date: 2018-03-05

Brief Summary

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.

Detailed 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.

Conditions

Hepatitis C

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

HCV GT1

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

Group Type: EXPERIMENTAL

Uprifosbuvir

Intervention Type: DRUG

Participants take 3 tablets each containing 150 mg uprifosbuvir q.d. by mouth.

Ruzasvir

Intervention Type: DRUG

Participants take 3 capsules each containing 60 mg RZR q.d. by mouth.

Ribavirin

Intervention Type: DRUG

RBV 200 mg capsules will be taken according to package instructions for a maximum of 16 weeks for any GT that meets virologic futility rules on uprifosbuvir + RZR alone.

HCV GT2

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

Group Type: EXPERIMENTAL

Uprifosbuvir

Intervention Type: DRUG

Participants take 3 tablets each containing 150 mg uprifosbuvir q.d. by mouth.

Ruzasvir

Intervention Type: DRUG

Participants take 3 capsules each containing 60 mg RZR q.d. by mouth.

Ribavirin

Intervention Type: DRUG

RBV 200 mg capsules will be taken according to package instructions for a maximum of 16 weeks for any GT that meets virologic futility rules on uprifosbuvir + RZR alone.

HCV GT3

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

Group Type: EXPERIMENTAL

Uprifosbuvir

Intervention Type: DRUG

Participants take 3 tablets each containing 150 mg uprifosbuvir q.d. by mouth.

Ruzasvir

Intervention Type: DRUG

Participants take 3 capsules each containing 60 mg RZR q.d. by mouth.

Ribavirin

Intervention Type: DRUG

RBV 200 mg capsules will be taken according to package instructions for a maximum of 16 weeks for any GT that meets virologic futility rules on uprifosbuvir + RZR alone.

HCV GT4

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

Group Type: EXPERIMENTAL

Uprifosbuvir

Intervention Type: DRUG

Participants take 3 tablets each containing 150 mg uprifosbuvir q.d. by mouth.

Ruzasvir

Intervention Type: DRUG

Participants take 3 capsules each containing 60 mg RZR q.d. by mouth.

Ribavirin

Intervention Type: DRUG

RBV 200 mg capsules will be taken according to package instructions for a maximum of 16 weeks for any GT that meets virologic futility rules on uprifosbuvir + RZR alone.

HCV GT5

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

Group Type: EXPERIMENTAL

Uprifosbuvir

Intervention Type: DRUG

Participants take 3 tablets each containing 150 mg uprifosbuvir q.d. by mouth.

Ruzasvir

Intervention Type: DRUG

Participants take 3 capsules each containing 60 mg RZR q.d. by mouth.

Ribavirin

Intervention Type: DRUG

RBV 200 mg capsules will be taken according to package instructions for a maximum of 16 weeks for any GT that meets virologic futility rules on uprifosbuvir + RZR alone.

HCV GT6

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

Group Type: EXPERIMENTAL

Uprifosbuvir

Intervention Type: DRUG

Participants take 3 tablets each containing 150 mg uprifosbuvir q.d. by mouth.

Ruzasvir

Intervention Type: DRUG

Participants take 3 capsules each containing 60 mg RZR q.d. by mouth.

Ribavirin

Intervention Type: DRUG

RBV 200 mg capsules will be taken according to package instructions for a maximum of 16 weeks for any GT that meets virologic futility rules on uprifosbuvir + RZR alone.

Interventions

Uprifosbuvir

Participants take 3 tablets each containing 150 mg uprifosbuvir q.d. by mouth.

Intervention Type: DRUG

Ruzasvir

Participants take 3 capsules each containing 60 mg RZR q.d. by mouth.

Intervention Type: DRUG

Ribavirin

RBV 200 mg capsules will be taken according to package instructions for a maximum of 16 weeks for any GT that meets virologic futility rules on uprifosbuvir + RZR alone.

Intervention Type: DRUG

Other Intervention Names

MK-3682; MK-8408

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

Lawitz E, Gane E, Feld JJ, Buti M, Foster GR, Rabinovitz M, Burnevich E, Katchman H, Tomasiewicz K, Lahser F, Jackson B, Shaughnessy M, Klopfer S, Yeh WW, Robertson MN, Hanna GJ, Barr E, Platt HL; C-BREEZE-2 Study Investigators. Efficacy and safety of a two-drug direct-acting antiviral agent regimen ruzasvir 180 mg and uprifosbuvir 450 mg for 12 weeks in adults with chronic hepatitis C virus genotype 1, 2, 3, 4, 5 or 6. J Viral Hepat. 2019 Sep;26(9):1127-1138. doi: 10.1111/jvh.13132. Epub 2019 Jul 11.

Reference Type: RESULT

PMID: 31108015 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2016-003227-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MK-3682-041

Identifier Type: OTHER

Identifier Source: secondary_id

3682-041

Identifier Type: -

Identifier Source: org_study_id