An Efficacy and Safety Study of Grazoprevir (MK-5172) + Elbasvir (MK-8742) in the Treatment of Chronic Hepatitis C Virus (HCV) Genotype (GT)1, 4, or 6 Infection in Treatment-Naïve Participants Who Are on Opiate Substitution Therapy (MK-5172-062)
Condition: Chronic Hepatitis C
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic
Intervention: Grazoprevir 100 mg/Elbasvir 50 mg FDC tablet (MK-5172A); Placebo to Grazoprevir 100 mg/Elbasvir 50 mg FDC tablet
Intervention description: Grazoprevir 100 mg/Elbasvir 50 mg FDC tablet, taken once daily by mouth for 12 weeks.; Placebo Grazoprevir 100 mg/Elbasvir 50 mg FDC tablet, taken once daily by mouth for 12 weeks.
Intervention MeSH terms: Grazoprevir
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 301.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a 2-part study. The purpose of Part A is to assess the efficacy and safety of
      grazoprevir (MK-5172) 100 mg in combination with elbasvir (MK-8742) 50 mg for 12 weeks in the
      treatment of chronic HCV GT1, GT4, or GT6 infection in treatment-naïve participants who are
      on opiate substitution therapy (OST). The primary hypothesis is that the percentage of
      participants who receive grazoprevir/elbasvir fixed-dose combination (FDC) in the Immediate
      Treatment Arm and achieve a Sustained Virologic Response 12 weeks after the end of all study
      therapy (SVR12) will be superior to 67%. In addition, participants who received at least 1
      dose of grazoprevir/elbasvir in Part A will be eligible to participate in Part B, which is a
      3-year observational follow-up.
    

Eligibility criteria:

        Inclusion Criteria:

        Part A

          -  Documented chronic HCV GT1, GT4, or GT6 infection with no evidence of GT2, GT3, GT5 or
             non-typeable genotypes and HCV ribonucleic acid (RNA) confirmed by screening lab
             results prior to randomization

          -  On opiate substitution therapy (OST; methadone, levamethadone, buprenorphine,
             naloxone, naltrexone) for at least 3 months prior to screening

          -  Treatment naïve to all HCV therapies

          -  Human Immunodeficiency Virus (HIV)-infected participants enrolled in this study must
             meet following criteria:

          -  Documented HIV infection

          -  Naïve to treatment with any antiretroviral therapy (ART) OR on HIV ART for at least 8
             weeks prior to study entry using a dual nucleoside reverse transcriptase inhibitor
             (NRTI) backbone of tenofovir or abacavir and either emtricitabine or lamivudine PLUS
             raltegravir (or dolutegravir or rilpivirine). Dose modifications or changes in ART
             during the 4 weeks prior to study entry (Day 1) are not permitted

          -  Cluster of differentiation 4 (CD4+) T-cell count >200 cells/mm^3 if on ART or >500
             cell/mm^3 if ART treatment naïve

          -  Undetectable plasma HIV-1 RNA at least 8 weeks prior to screening if on ART or <50,000
             copies/mL if ART treatment naïve

          -  Participants with HIV-1 infection and on ART must have at least one viable
             antiretroviral regimen alternative beyond their current regimen in the event of HIV
             virologic failure or the development of anti-retroviral drug resistance

          -  Females who are of reproductive potential must agree to avoid becoming pregnant while
             receiving study drug and for 14 days after the last dose of study drug by complying
             with one of the following: (1) practice abstinence from heterosexual activity OR (2)
             use (or have her partner use) acceptable contraception during heterosexual activity

        Part B

          -  Received at least one dose of grazoprevir in combination with elbasvir in Part A.
             Receiving OST and keeping >80% of scheduled appointments while on OST were not
             required for Part B.

        Exclusion Criteria:

        Part A

          -  Evidence of decompensated liver disease

          -  For participants with cirrhosis, participants who are Child-Pugh Class B or C or who
             have a Pugh-Turcotte (CPT) score >6

          -  Is co-infected with hepatitis B virus

          -  Has cirrhosis and liver imaging within 6 months of Day 1 showing evidence of
             hepatocellular carcinoma (HCC) or is under evaluation for HCC

          -  Currently using or intends to use barbiturates during the treatment period of this
             study

          -  Is a female and is pregnant or breast-feeding, or expecting to conceive or donate eggs
             from Day 1 or anytime during treatment, and 14 days after the last dose of study
             medication, or longer if dictated by local regulations

          -  Any medical condition requiring or likely to require chronic systemic administration
             of corticosteroids, Tumor Necrosis Factor (TNF) antagonists, or other
             immunosuppressant drugs during the course of the trial

          -  Evidence or history of chronic hepatitis not caused by HCV

        Part B

          -  Mentally or legally incapacitated, has significant emotional problems at the time of
             pre-study screening visit or expected during the conduct of the study or has a history
             of a clinically significant psychiatric disorder which, in the opinion of the
             investigator, would interfere with the study procedures

          -  Has a medical condition or personal circumstance which, in the opinion of the
             investigator and/or Sponsor, places the participant at unnecessary risk through
             continued participation in the trial or does not allow the participant to adhere to
             the requirements of the protocol