Efficacy and Safety of Elbasvir (MK-8742) + Grazoprevir (MK-5172) in Treatment-Naïve/Treatment-Experienced (TN/TE) French Participants With Hepatitis C Virus (HCV) Genotype 4 (GT4) Infection (MK-5172-096)

Study Overview
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Brief Summary
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The purpose of this study was to evaluate the efficacy of 8 and 12 weeks of treatment with a fixed dose combination (FDC) of elbasvir (EBR) 50 mg + grazoprevir (GZR) 100 mg (i.e., MK-5172A) as assessed by the percentage of participants with hepatitis C virus (HCV) genotype (GT) 4 infection that achieve sustained virologic response (HCV ribonucleic acid [RNA] < Lower Limit of Quantification [LLOQ]) 12 weeks after the end of study therapy (SVR12). This study also evaluated the safety and tolerability of EBR/GZR.

Official Title
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A Multi-Site, Open-Label, Partially-Randomized Trial of the Efficacy and Safety of Fixed Dose Elbasvir/Grazoprevir (EBR/GZR) Based Regimens in French Subjects With Chronic Hepatitis C Virus (HCV) Genotype 4 Infection

Conditions
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Hepatitis C Virus (HCV) Infection

Intervention / Treatment
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* Drug: EBR/GZR (50 mg/100 mg) FDC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be a current resident of France Have HCV RNA (≥ 10,000 IU/mL in peripheral blood) at the time of screening Have documented chronic HCV GT4 (with no evidence of non-typeable or mixed genotype) infection Have liver biopsy performed within 24 months of Day 1 of this study (if participant has cirrhosis, there is no time restriction on biopsy), or have FibroScan® performed within 12 months of Day 1 of this study with interpretable result in kilopascals (kPa) as follows: Fibrosis score of F0-F2, Fibrosis score of F3, or Cirrhosis (F4) Have a prior treatment history of either HCV TN or HCV TE with interferon (IFN) +/- ribavirin (RBV) +/- Sofosbuvir (SOF) (on-treatment failure, relapser, or other/intolerant) 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 If Human Immunodeficiency Virus (HIV) co-infected, then have HIV-1 infection documented prior to screening Exclusion Criteria: Had prior treatment (defined as 1 dose or more) with direct-acting antiviral (DAA) therapy Has evidence of decompensated liver disease manifested by the presence of or history of ascites, esophageal or gastric variceal bleeding, hepatic encephalopathy, or other signs or symptoms of active advanced liver disease Classified as Child-Pugh B or C or has a Child Pugh-Turcotte score (CPT) > 6 Has cirrhosis and liver imaging within 6 months of Day 1 showing evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC Hepatitis B virus surface antigen (HBsAg) positive at screening. Participants who are HBsAg negative and hepatitis B core antibody (anti-HBc) positive at screening may be included Under evaluation for active or suspected malignancy, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer Currently participating or has participated in a study with an investigational compound within 30 days of signing informed consent and is not willing to refrain from participating in another such study during the course of this study

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: EBR/GZR for 8 Weeks<br>Treatment-naïve participants with stage 0-2 fibrosis (F0-F2) receive FDC of EBR/GZR (50 mg/100 mg) for 8 weeks, with 24 weeks of follow-up. | Drug: EBR/GZR (50 mg/100 mg) FDC<br>* One FDC tablet taken once daily by mouth for 8 or 12 weeks depending upon randomization.<br>* Other names: MK-5172A;|
| Experimental: Arm 2: EBR/GZR for 12 Weeks<br>Treatment-naïve participants with F0-F2 stage fibrosis, treatment-naïve participants with F3-F4 stage fibrosis, and treatment-experienced participants with F0-F4 stage fibrosis receive FDC of EBR/GZR (50 mg/100 mg) for 12 weeks, with 24 weeks of follow-up. | Drug: EBR/GZR (50 mg/100 mg) FDC<br>* One FDC tablet taken once daily by mouth for 8 or 12 weeks depending upon randomization.<br>* Other names: MK-5172A;|

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 End of Treatment (SVR12) | The percentage of participants to achieve SVR12 was determined for each arm (SVR12 was defined as HCV ribonucleic acid [RNA] < lower limit of quantification [LLOQ] at 12 weeks after the end of all study therapy). Plasma HCV RNA was measured using the COBAS™ AmpliPrep/COBAS™ TaqMan HCV Test, v2.0®, which has a LLOQ of 15 IU/mL. | 12 weeks after completing study treatment (Arm 1: Week 20 / Arm 2: Week 24) | 
| Number of Participants With ≥ 1 Adverse Events (AEs) | An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. | Up to 14 weeks | 
| Number of Participants Who Discontinued From Study Treatment Due to an AE | An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. | Up to Study Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After End of Treatment (SVR24) | The percentage of participants to achieve SVR24 was determined for each arm (SVR24 was defined as HCV RNA < LLOQ at 24 weeks after the end of all study therapy). Plasma HCV RNA was measured using the COBAS™ AmpliPrep/COBAS™ TaqMan HCV Test, v2.0®, which has a LLOQ of 15 IU/mL. | 24 weeks after completing study treatment (Arm 1: Week 32 / Arm 2: Week 36) | 
| Prevalence of Baseline NS3 Resistance-Associated Substitutions (RASs) to EBR or GZR | Blood samples for viral resistance assays were collected at Baseline (Day 1) and analyzed for substitutions in the NS3 gene region. Results are pooled for all participants with baseline sequencing data available, and the number of participants with RASs is reported according HCV genotype. Resistance-associated substitutions are defined as amino acid substitutions that confer reduced susceptibility to a direct-acting antiviral (DAA) and may contribute to virologic failure. The prevalence of baseline substitutions in participants infected with HCV GT4 subtypes was assessed by evaluating amino acid substitutions in NS3. | Day 1 | 
| Prevalence of Baseline NS5A RASs to EBR or GZR | Blood samples for viral resistance assays were collected at Baseline (Day 1) and analyzed for substitutions in the NS5A gene region. Results are pooled for all participants with baseline sequencing data available, and the number of participants with RASs is reported according HCV genotype. Resistance-associated substitutions are defined as amino acid substitutions that confer reduced susceptibility to a DAA and may contribute to virologic failure. The prevalence of baseline substitutions in participants infected with HCV GT4 subtypes was assessed by evaluating amino acid substitutions in NS5A. | Day 1 |