Grazoprevir (MK-5172) and Elbasvir (MK-8742) Combination for Chronic Hepatitis C Virus (HCV) Genotypes 1, 4, and 6 (MK-5172-065)

Phase 3

Completed

Brief Summary: This is a randomized, multi-site, placebo-controlled trial of a fixed dose combination (FDC) of grazoprevir (MK-5172) 100 mg + elbasvir (MK-8742) 50 mg in participants with chronic Hepatitis C Virus (HCV) genotype (GT) 1, GT4 or GT6 with inherited blood disorders. The primary hypothesis is that the proportion of participants treated with grazoprevir+elbasvir achieving Sustained Virologic Response (SVR) 12 weeks after the end of all study therapy (SVR12) will be greater than the reference rate of 40%.

Recruitment & Eligibility

Inclusion Criteria

has HCV GT1, GT4, or GT6 with sickle cell anemia, thalassemia, or hemophilia/von Willebrand disease
has cirrhosis or is non-cirrhotic
is human immunodeficiency virus (HIV) coinfected or not infected with HIV
is a female of non childbearing potential, or is male or female and uses an acceptable method(s) of contraception

Exclusion Criteria

has evidence of decompensated liver disease
is coinfected with hepatitis B
has had a malignancy ≤5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer
has hepatocellular carcinoma (HCC) or is under evaluation for HCC
has clinically-relevant drug or alcohol abuse within 12 months of screening

Arm && Interventions

Group	Intervention	Description
Immediate Treatment	Grazoprevir + Elbasvir	Participants will take grazoprevir 100 mg + elbasvir 50 mg once daily during the 12-week treatment period and then will be monitored for safety during a 24-week follow-up period.
Deferred Treatment	Grazoprevir + Elbasvir	Participants will take placebo tablets once daily during the 12-week treatment period and will then be monitored for safety during a 4-week follow-up period. Participants will then begin open-label treatment with grazoprevir 100 mg + elbasvir 50 mg for a 12-week treatment period and will then be monitored for safety during a 24-week follow-up period.
Deferred Treatment	Placebo	Participants will take placebo tablets once daily during the 12-week treatment period and will then be monitored for safety during a 4-week follow-up period. Participants will then begin open-label treatment with grazoprevir 100 mg + elbasvir 50 mg for a 12-week treatment period and will then be monitored for safety during a 24-week follow-up period.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Discontinuing From Study Treatment Due to an AE(s)	Up to Week 12	An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment.
Percentage of Participants Experiencing an Adverse Event (AE)	Up to Week 14	An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment.
Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After Completing Study Therapy (SVR12)	12 weeks after completing study therapy (Week 24)	The percentage of participants in the both arms achieving SVR12 (i.e., HCV riboncleic acid \[RNA\] level below the lower limit of quantification \[LLoQ\] 12 weeks after completing study therapy) was determined. HCV RNA levels were measured using the Roche COBAS™ Taqman™ HCV Test v2.0 (High Pure System), which has a LLoQ of \<15 IU/mL.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Completing Study Therapy (SVR24)	24 weeks after completing study therapy (Week 36)	The percentage of participants in both arms achieving SVR24 (i.e., HCV RNA level below the LLoQ 24 weeks after completing study therapy) was determined. HCV RNA levels were measured using the Roche COBAS™ Taqman™ HCV Test v2.0 (High Pure System), which has a LLoQ of \<15 IU/mL.