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

Study Overview
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Brief Summary
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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%.

Official Title
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A Phase III Double Blind Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-5172 and MK-8742 in Subjects With Chronic HCV GT1, GT4 and GT6 Infection With Inherited Blood Disorders With and Without HIV Co-Infection

Conditions
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Hepatitis C

Intervention / Treatment
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* Drug: Grazoprevir + Elbasvir
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Immediate Treatment<br>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. | Drug: Grazoprevir + Elbasvir<br>* FDC tablet containing grazoprevir 100 mg + elbasvir 50 mg taken once daily by mouth.<br>|
| Placebo Comparator: Deferred Treatment<br>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. | Drug: Grazoprevir + Elbasvir<br>* FDC tablet containing grazoprevir 100 mg + elbasvir 50 mg taken once daily by mouth.<br>Drug: Placebo<br>* Placebo tablets matching grazoprevir + elbasvir FDC tablets taken once daily by mouth.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After Completing Study Therapy (SVR12) | 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. | 12 weeks after completing study therapy (Week 24) | 
| Percentage of Participants Experiencing an Adverse Event (AE) | An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. | Up to Week 14 | 
| Percentage of Participants Discontinuing From Study Treatment Due to an AE(s) | An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. | Up to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Completing Study Therapy (SVR24) | 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. | 24 weeks after completing study therapy (Week 36) |