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)

NCT02759315 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 3682-035MK-3682-035
• Study Type: interventional
• Target: 160
• Locations: 0 countries
• Sites: N/A

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

Outcome Measures

Primary Outcomes (4)

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

  The percentage of participants in each arm achieving SVR12 was determined. SVR12 was defined as HCV ribonucleic acid (RNA) levels in plasma \< lower limit of quantification (LLOQ) 12 weeks after completing study treatment. Plasma levels of HCV RNA were measured with the COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay, which has a LLOQ of 15 IU/mL.

  Week 24 (12 weeks after completing study therapy)

• Percentage of Participants With ≥1 Adverse Events (AEs)

  The percentage of participants experiencing an AE during the treatment period and first 2 weeks of follow-up was determined. An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

  Up to Week 14 (up to 2 weeks after completing study therapy)

• Percentage of Participants Withdrawing From Study Therapy Due to an AE

  The percentage of participants discontinuing from study therapy during the treatment period was determined. An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

  Up to Week 12

• Percentage of Participants With ≥1 Events of Clinical Interest (ECIs)

  The percentage of participants with ECIs was determined. ECIs were defined as the following: 1) an overdose of study drug; 2) first instance of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>500 IU/L; 3) first instance of ALT or AST \>3x nadir and \>3x upper limit of normal (ULN); 4) first instance of estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73 m\^2; or 4) first instance of serum creatinine \>1.3x ULN and elevated from baseline.

  Up to Week 14 (up to 2 weeks after completing study therapy)

Secondary Outcomes (3)

• Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Completing Study Therapy (SVR24)

  Week 36 (24 weeks after completing study therapy)

• Percentage of Participants With Virologic Failure (VF)

  12 weeks after the end of all study therapy (24 weeks)

• Percentage of Participants With Baseline Resistance-Associated Substitutions (RAS) Achieving SVR12

  12 weeks after the end of all study therapy (24 weeks)

Study Arms (6)

GT1: Uprifosbuvir 450 mg + Ruzasvir 60 mg

EXPERIMENTAL

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.

Drug: Uprifosbuvir 450 mg; Drug: Ruzasvir 60 mg

GT2: Uprifosbuvir 450 mg + Ruzasvir 60 mg

EXPERIMENTAL

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.

Drug: Uprifosbuvir 450 mg; Drug: Ruzasvir 60 mg

GT3: Uprifosbuvir 450 mg + Ruzasvir 60 mg

EXPERIMENTAL

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.

Drug: Uprifosbuvir 450 mg; Drug: Ruzasvir 60 mg

GT4: Uprifosbuvir 450 mg + Ruzasvir 60 mg

EXPERIMENTAL

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.

Drug: Uprifosbuvir 450 mg; Drug: Ruzasvir 60 mg

GT5: Uprifosbuvir 450 mg + Ruzasvir 60 mg

EXPERIMENTAL

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.

Drug: Uprifosbuvir 450 mg; Drug: Ruzasvir 60 mg

GT6: Uprifosbuvir 450 mg + Ruzasvir 60 mg

EXPERIMENTAL

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.

Drug: Uprifosbuvir 450 mg; Drug: Ruzasvir 60 mg

Interventions

Uprifosbuvir 450 mg DRUG

450 mg administered as 3 x 150 mg oral tablets

Also known as: MK-3682

GT1: Uprifosbuvir 450 mg + Ruzasvir 60 mg; GT2: Uprifosbuvir 450 mg + Ruzasvir 60 mg; GT3: Uprifosbuvir 450 mg + Ruzasvir 60 mg; GT4: Uprifosbuvir 450 mg + Ruzasvir 60 mg; GT5: Uprifosbuvir 450 mg + Ruzasvir 60 mg; GT6: Uprifosbuvir 450 mg + Ruzasvir 60 mg

Ruzasvir 60 mg DRUG

60 mg administered as 6 x 10 mg oral capsules

Also known as: MK-8408

GT1: Uprifosbuvir 450 mg + Ruzasvir 60 mg; GT2: Uprifosbuvir 450 mg + Ruzasvir 60 mg; GT3: Uprifosbuvir 450 mg + Ruzasvir 60 mg; GT4: Uprifosbuvir 450 mg + Ruzasvir 60 mg; GT5: Uprifosbuvir 450 mg + Ruzasvir 60 mg; GT6: Uprifosbuvir 450 mg + Ruzasvir 60 mg

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (2)

• 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.

  PMID: 30739366 RESULT

• 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 DERIVED

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

uprifosbuvir; ruzasvir

Condition Hierarchy (Ancestors)

Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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: April 29, 2016
• First Posted: May 3, 2016
• Study Start: May 3, 2016
• Primary Completion: July 27, 2017
• Study Completion: November 16, 2017
• Last Updated: June 26, 2019
• Results First Posted: August 6, 2018

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will share