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

NCT02956629 | Terminated Phase 2 Results FDA Drug

• 3 other identifiers: 3682-0412016-003227-37MK-3682-041
• Study Type: interventional
• Target: 282
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Hepatitis C

Outcome Measures

Primary Outcomes (7)

• Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Completing Study Therapy (SVR12)

  Plasma levels of hepatitis C virus (HCV) ribonucleic acid (RNA) were measured using the Roche COBAS® AmpliPrep/COBAS® TaqMan® HCV Test, v2.0 on blood samples drawn from participants. SVR12 is the absence of detectable RNA of the hepatitis C virus, (\<lower limit of quantification \[LLOQ\] of 15 IU/mL) for at least 12 weeks after completing treatment.

  12 weeks after completing study therapy (Week 24)

• Percentage of Participants Experiencing an Adverse Event (AE)

  An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example ), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change infrequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.

  Up to Week 14

• Percentage of Participants Experiencing an AE of Clinical Importance (ECI)

  Adverse events of clinical importance, excluding overdoses include, but is not limited to, significant changes in alanine aminotransferase, aspartate aminotransferase, blood creatinine, glomerular filtration rate or hepatitis B reactivation.

  Up to Week 14

• Percentage of Participants Experiencing a Serious Adverse Event (SAE)

  A serious adverse event (SAE) is any AE occurring at any dose or during any use of Sponsor's product that: results in death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing inpatient hospitalization; is a congenital anomaly/birth defect; is an other important medical event; is a cancer; is associated with an overdose.

  Up to Week 14

• Percentage of Participants Experiencing a Drug-related AE

  An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example ), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change infrequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. A drug-related AE is determined by the investigator to be related to the use of the drug.

  Up to Week 14

• Percentage of Participants Experiencing a Drug-related SAE

  A SAE is any AE occurring at any dose or during any use of Sponsor's product that: results in death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing inpatient hospitalization; is a congenital anomaly/birth defect; is an other important medical event; is a cancer; is associated with an overdose. A drug-related SAE is determined by the investigator to be related to the use of the drug.

  Up to Week 14

• Percentage of Participants Discontinuing Study Therapy Due to an AE

  An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example ), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change infrequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.

  Up to Week 12

Secondary Outcomes (2)

• Percentage of Participants With SVR 24 Weeks After Completing Study Therapy (SVR24)

  24 weeks after completing study therapy (Week 36)

• Percentage of Participants With Virologic Failure

  Up to Week 24

Study Arms (6)

HCV GT1

EXPERIMENTAL

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

Drug: Uprifosbuvir; Drug: Ruzasvir; Drug: Ribavirin

HCV GT2

EXPERIMENTAL

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

Drug: Uprifosbuvir; Drug: Ruzasvir; Drug: Ribavirin

HCV GT3

EXPERIMENTAL

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

Drug: Uprifosbuvir; Drug: Ruzasvir; Drug: Ribavirin

HCV GT4

EXPERIMENTAL

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

Drug: Uprifosbuvir; Drug: Ruzasvir; Drug: Ribavirin

HCV GT5

EXPERIMENTAL

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

Drug: Uprifosbuvir; Drug: Ruzasvir; Drug: Ribavirin

HCV GT6

EXPERIMENTAL

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

Drug: Uprifosbuvir; Drug: Ruzasvir; Drug: Ribavirin

Interventions

Uprifosbuvir DRUG

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

Also known as: MK-3682

HCV GT1; HCV GT2; HCV GT3; HCV GT4; HCV GT5; HCV GT6

Ruzasvir DRUG

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

Also known as: MK-8408

HCV GT1; HCV GT2; HCV GT3; HCV GT4; HCV GT5; HCV GT6

Ribavirin 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 GT1; HCV GT2; HCV GT3; HCV GT4; HCV GT5; HCV GT6

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• 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.

  PMID: 31108015 RESULT

MeSH Terms

Conditions

Hepatitis C

Interventions

uprifosbuvir; ruzasvir; Ribavirin

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2016
• First Posted: November 7, 2016
• Study Start: November 16, 2016
• Primary Completion: December 22, 2017
• Study Completion: March 5, 2018
• Last Updated: February 2, 2021
• Results First Posted: December 26, 2018

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will share