Efficacy and Safety of Uprifosbuvir (MK-3682) With Ruzasvir (MK-8408) in Adults With Chronic Hepatitis C Genotype 1, 2, 3, 4, 5 or 6 Infection (MK-3682-035)

NCT ID: NCT02759315

Last Updated: 2019-06-26

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 160 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-03
• Study Completion Date: 2017-11-16

Brief Summary

This study is an open-label, multi-center trial to evaluate the novel 2-drug regimen of uprifosbuvir (MK-3682) 450 mg and ruzasvir (MK-8408) 60 mg in participants with chronic hepatitis C virus (HCV) genotype (GT)1, GT2, GT3, GT4, GT5, or GT6 infection. The impact of the study treatment regimen on the percentage of participants with undetectable HCV ribonucleic acid [RNA] 12 weeks after completing study treatment (SVR12) will be evaluated.

Conditions

Hepatitis C, Chronic

Study Design

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

Study Groups

GT1: Uprifosbuvir 450 mg + Ruzasvir 60 mg

Participants will receive an oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast and at least one hour before a meal, once a day, for 12 weeks. The GT1 Arm is sub-divided into GT1a and GT1b Arms. GT1a Arm will enroll approximately 35 participants including up to 10 participants who are compensated cirrhotics and GT1b Arm will enroll approximately 15 participants including up to 5 participants who are compensated cirrhotics.

Group Type: EXPERIMENTAL

Uprifosbuvir 450 mg

Intervention Type: DRUG

450 mg administered as 3 x 150 mg oral tablets

Ruzasvir 60 mg

Intervention Type: DRUG

60 mg administered as 6 x 10 mg oral capsules

GT2: Uprifosbuvir 450 mg + Ruzasvir 60 mg

Participants will receive an oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast and at least one hour before a meal, once a day, for 12 weeks. The GT2 Arm of the study will enroll approximately 50 participants including up to 15 participants who are compensated cirrhotics.

Group Type: EXPERIMENTAL

Uprifosbuvir 450 mg

Intervention Type: DRUG

450 mg administered as 3 x 150 mg oral tablets

Ruzasvir 60 mg

Intervention Type: DRUG

60 mg administered as 6 x 10 mg oral capsules

GT3: Uprifosbuvir 450 mg + Ruzasvir 60 mg

Participants will receive an oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast and at least one hour before a meal, once a day, for 12 weeks. The GT3 Arm of the study will enroll approximately 50 participants including up to 15 participants who are compensated cirrhotics.

Group Type: EXPERIMENTAL

Uprifosbuvir 450 mg

Intervention Type: DRUG

450 mg administered as 3 x 150 mg oral tablets

Ruzasvir 60 mg

Intervention Type: DRUG

60 mg administered as 6 x 10 mg oral capsules

GT4: Uprifosbuvir 450 mg + Ruzasvir 60 mg

Participants will receive an oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast and at least one hour before a meal, once a day, for 12 weeks. The GT4 Arm of the study will enroll approximately 50 participants including up to 15 participants who are compensated cirrhotics.

Group Type: EXPERIMENTAL

Uprifosbuvir 450 mg

Intervention Type: DRUG

450 mg administered as 3 x 150 mg oral tablets

Ruzasvir 60 mg

Intervention Type: DRUG

60 mg administered as 6 x 10 mg oral capsules

GT5: Uprifosbuvir 450 mg + Ruzasvir 60 mg

Participants will receive an oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast and at least one hour before a meal, once a day, for 12 weeks. The GT5 Arm of the study will enroll approximately 25 participants including both non- cirrhotics and compensated cirrhotics.

Group Type: EXPERIMENTAL

Uprifosbuvir 450 mg

Intervention Type: DRUG

450 mg administered as 3 x 150 mg oral tablets

Ruzasvir 60 mg

Intervention Type: DRUG

60 mg administered as 6 x 10 mg oral capsules

GT6: Uprifosbuvir 450 mg + Ruzasvir 60 mg

Participants will receive an oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast and at least one hour before a meal, once a day, for 12 weeks. The GT6 Arm of the study will enroll approximately 25 participants including both non- cirrhotics and compensated cirrhotics.

Group Type: EXPERIMENTAL

Uprifosbuvir 450 mg

Intervention Type: DRUG

450 mg administered as 3 x 150 mg oral tablets

Ruzasvir 60 mg

Intervention Type: DRUG

60 mg administered as 6 x 10 mg oral capsules

Interventions

Uprifosbuvir 450 mg

450 mg administered as 3 x 150 mg oral tablets

Intervention Type: DRUG

Ruzasvir 60 mg

60 mg administered as 6 x 10 mg oral capsules

Intervention Type: DRUG

Other Intervention Names

MK-3682; MK-8408

Eligibility Criteria

Inclusion Criteria

• Has hepatitis C virus (HCV) ribonucleic acid (RNA) at the time of screening
• Has documented chronic HCV genotype (GT)1, GT2, GT3, GT4, GT5, or GT6 with no evidence of non-typeable or mixed GT infection
• Is otherwise healthy as determined by the medical history, physical examination, electrocardiogram (ECG), and clinical laboratory measurements performed at the time of screening
• Has absence of cirrhosis or has compensated cirrhosis
• Is HCV treatment-naïve or has experienced virologic failure after completing a prior interferon-containing regimen
• Is of non-childbearing potential or agrees to avoid becoming pregnant or impregnating a partner beginning at least 2 weeks prior to administration of the initial dose of study drug and for 14 days after the last dose of study drug
• For human immunodeficiency virus (HIV) co-infected participants: is not currently on antiretroviral therapy (ART) and has no plans to initiate ART treatment while participating in this study Or has well-controlled HIV on ART

Exclusion Criteria

• Is mentally or legally incapacitated, has significant emotional problems (at screening or expected during the study) or has a history of a clinically significant psychiatric disorder that would interfere with the study procedures.
• Has evidence of decompensated liver disease manifested by the presence of or history of ascites, esophageal or gastric variceal bleeding, hepatic encephalopathy or other signs or symptoms of advanced liver disease
• Is Child-Pugh Class B or C or has a Pugh-Turcotte (CPT) score >6 if cirrhotic
• Is co-infected with Hepatitis B Virus
• Has a history of opportunistic infection in the preceding 6 months prior to screening if co-infected with HIV
• Has a history of malignancy ≤5 years prior to study start (except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer or carcinoma in situ) or is under evaluation for other active or suspected malignancy
• Has cirrhosis and liver imaging within 6 months prior to study start showing evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC
• Is taking any medications or herbal supplements restricted by the study entry criteria in the period from ≤2 weeks prior to study start through 2 weeks after the last dose of study drug
• Has clinically-relevant drug or alcohol abuse within 12 months of study start
• Has participated in any clinical study of an investigational product within 30 days prior to the first dose of study drug
• Is female and is pregnant or breastfeeding, or expecting to conceive or donate eggs from at least 2 weeks prior to study start and 14 days after the last dose of study drug
• Is male and is expecting to donate sperm from at least 2 weeks prior to Day 1 until 14 days after the last dose of study drug
• Has or has had any of the following: organ transplants (including hematopoietic stem cell transplants) other than cornea and hair; poor venous access; history of gastric surgery; or history of malabsorption disorders
• Has any cardiac abnormalities/dysfunction including but not limited to: unstable angina; unstable congestive heart failure; or unstable arrhythmia
• Has a history of a medical/surgical condition that resulted in hospitalization within 3 months prior to study start, other than for minor elective procedures
• Has any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids, tumor necrosis factor (TNF) antagonists, or other immunosuppressant drugs during the study
• Has evidence of history of chronic 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, Poordad F, Anderson LJ, Vesay M, Kelly MM, Liu H, Gao W, Fernsler D, Asante-Appiah E, Robertson MN, Hanna GJ, Barr E, Butterton J, Kowdley KV, Hassanein T, Sahota A, Gordon SC, Yeh WW. Efficacy and safety of ruzasvir 60 mg and uprifosbuvir 450 mg for 12 weeks in adults with chronic hepatitis C virus genotype 1, 2, 3, 4 or 6 infection. J Viral Hepat. 2019 Jun;26(6):675-684. doi: 10.1111/jvh.13079. Epub 2019 Mar 12.

Reference Type: RESULT

PMID: 30739366 (View on PubMed)

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: DERIVED

PMID: 31108015 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

MK-3682-035

Identifier Type: OTHER

Identifier Source: secondary_id

3682-035

Identifier Type: -

Identifier Source: org_study_id