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) (C-EDGE CO-STAR)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 3

Conditions: Chronic Hepatitis C

Treatments: Drug: Placebo to Grazoprevir 100 mg/Elbasvir 50 mg FDC tablet; Drug: Grazoprevir 100 mg/Elbasvir 50 mg FDC tablet (MK-5172A)

Study type: Interventional

Funder types: Industry

Identifiers

NCT02105688

MK-5172-062 (Other Identifier)

2014-000343-32 (EudraCT Number)

5172-062

Details and patient eligibility

About

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.

Enrollment: 301 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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301 participants in 2 patient groups, including a placebo group

Immediate Treatment Arm: Grazoprevir/Elbasvir

Experimental group

Description:

In Part A, participants receive grazoprevir 100 mg plus elbasvir 50 mg FDC (MK-5172A) once daily for 12 weeks (blinded) and were followed-up for 24 weeks. In Part B, participants could enroll in a 3-year follow-up period where they were followed every 6 months for 3 years in an observational cohort (no treatment was administered during Part B).

Treatment:

Drug: Grazoprevir 100 mg/Elbasvir 50 mg FDC tablet (MK-5172A)

Deferred Treatment Arm: Placebo > Grazoprevir/Elbasvir

Placebo Comparator group

Description:

In Part A, participants receive placebo to MK-5172A once daily for 12 weeks (blinded), followed by 4 weeks of follow-up. Afterwards, participants received 12 weeks of open-label treatment with the MK-5172A FDC and were followed-up for 24 weeks. In Part B, participants could enroll in a 3-year follow-up period where they were followed every 6 months for 3 years in an observational cohort (no treatment was administered during Part B).

Treatment:

Drug: Grazoprevir 100 mg/Elbasvir 50 mg FDC tablet (MK-5172A)

Drug: Placebo to Grazoprevir 100 mg/Elbasvir 50 mg FDC tablet