Clinical trial NCT01932762: Efficacy and Safety of Combination Grazoprevir (MK-5172) + Elbasvir (MK-8742) + Ribavirin (RBV) in Genotype 2 Hepatitis C Infection (MK-5172-047)
Official title: A Phase II Clinical Trial to Evaluate the Efficacy and Safety of a Combination Regimen of MK-5172 With/Without MK-8742 and/or Ribavirin (RBV) in Treatment-naive Subjects With Chronic Hepatitis C Genotype 2, 4, 5 and 6 Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis C
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2013-08-30
Enrollment: 98
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multi-site, open-label trial evaluating the safety and efficacy of 100 mg of grazoprevir (MK-5172) used in combination with or without 50 mg of elbasvir (MK-8742) and/or ribavirin (RBV) in treating non-cirrhotic treatment-naïve participants with chronic genotype (GT) 2, 4, 5, and 6 hepatitis C infection.

In Part A there is no randomization or stratification; all GT2 participants will be assigned to arm A1. In Part B, all GT2 participants will be assigned to Arm B1 and all participants with GT4, GT5 and GT6 will be randomized in a 1:1 ratio to either Arm 3 or Arm 4 with stratification by genotype.


Eligibility criteria: Inclusion Criteria:

Parts A and B: -Body weight ≥50 kg (111 lbs) and ≤ 125 kg (275 lbs) -Has absence of cirrhosis -Agrees to use two acceptable methods of birth control from at least 2 weeks prior to Day 1 and continue until at least 6 months after last dose of study drug, or longer if dictated by local regulations (for female participant who is of childbearing potential or male participant with female sexual partner who is of childbearing potential).

Part A only: -Has chronic HCV GT2 infection Part B only: -Has chronic HCV GT2, GT4, GT5, or GT6 infection

Exclusion Criteria:

Parts A and B:

-Is not treatment naïve (participant has had previous treatment with any interferon, RBV, approved or experimental direct acting antiviral(s), or other investigational therapies for HCV) -Is determined to be coinfected with hepatitis B virus (HBsAg positive) or HIV -Has evidence of, or is under evaluation for, hepatocellular carcinoma (HCC) -Has a clinical diagnosis of substance abuse including the following specified drugs within specified timeframes: Alcohol, intravenous drugs, inhalational, psychotropics, narcotics, cocaine use, prescription or over-the-counter drugs (within 1 year of the screening visit), is receiving opiate agonist substitution therapy (within 1 year of screening visit), or excessive historic marijuana use -Has evidence of active or suspected malignancy, or a history of malignancy, within the last 5 years -Female participant who is pregnant, lactating, expecting to conceive or donate eggs, or is of childbearing potential and unwilling to commit to two methods of birth control throughout treatment and after the completion of all treatment, or male participant who is planning to impregnate or provide sperm donation or has a female sexual partner of childbearing potential and is unwilling to commit to using a two methods of birth control throughout treatment and after the completion of all treatment -Has evidence or history of chronic hepatitis not caused by HCV, including but not limited to nonalcoholic steatohepatitis (NASH), drug-induced hepatitis, and autoimmune hepatitis. -Has uncontrolled diabetes (documented HbA1c \>8.5%)

Part A only:

-Has non GT2 HCV infection

Part B only:

-Has HCV infection with a genotype other than GT2, GT4, GT5 or GT6

Primary outcomes:
measure: Percentage of Participants With Sustained Virologic Response 12 Weeks After The End of Study Therapy (SVR12)
timeFrame: 12 weeks after end of all therapy (Study Week 24)
measure: Percentage of Participants With Adverse Events (AEs), Serious AEs (SAEs), Drug-Related AEs, Drug-Related SAEs, or Discontinuation of Study Treatment Due to AE During the Treatment Period and First 14 Follow-up Days
timeFrame: Treatment period plus the first 14 days of follow-up (up to 14 weeks)
Secondary outcomes:
measure: Mean Time to First Achievement of Undetectable HCV RNA During Treatment
timeFrame: From TW1 until first achievement of undetectable HCV RNA (up to 12 weeks)
measure: Percentage of Participants Achieving Undetectable HCV RNA During Treatment By Timepoint
timeFrame: From TW 2 through TW 12 (up to 12 weeks)
measure: Percentage of Participants Achieving HCV RNA <25 IU/mL During Treatment By Timepoint
timeFrame: From TW 2 through TW 12 (up to 12 weeks)
measure: Percentage of Participants Achieving SVR4
timeFrame: 4 weeks after end of all therapy (Study Week 16)
measure: Percentage of Participants Achieving SVR24
timeFrame: 24 weeks after end of all therapy (Study Week 36)
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Brown A, Hezode C, Zuckerman E, Foster GR, Zekry A, Roberts SK, Lahser F, Durkan C, Badshah C, Zhang B, Robertson M, Wahl J, Barr E, Haber B; C-SCAPE Study Investigators. Efficacy and safety of 12 weeks of elbasvir +/- grazoprevir +/- ribavirin in participants with hepatitis C virus genotype 2, 4, 5 or 6 infection: The C-SCAPE study. J Viral Hepat. 2018 May;25(5):457-464. doi: 10.1111/jvh.12801. Epub 2018 Mar 14.
citation: Asselah T, Reesink H, Gerstoft J, de Ledinghen V, Pockros PJ, Robertson M, Hwang P, Asante-Appiah E, Wahl J, Nguyen BY, Barr E, Talwani R, Serfaty L. Efficacy of elbasvir and grazoprevir in participants with hepatitis C virus genotype 4 infection: A pooled analysis. Liver Int. 2018 Sep;38(9):1583-1591. doi: 10.1111/liv.13727. Epub 2018 Mar 31.