Grazoprevir (MK-5172) and Elbasvir (MK-8742) Combination in Treatment-Naïve Hepatitis C Virus Participants (MK-5172-067)

Study Overview
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Brief Summary
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This is a randomized, parallel-group, placebo-controlled, multi-site, multinational, double-blind followed by open label period, Phase 3 trial of 100 mg of grazoprevir (MK-5172) in combination with 50 mg of elbasvir (MK-8742) (grazoprevir/elbasvir fixed-dose combination [FDC]) in treatment-naïve (TN) participants with chronic hepatitis C virus (HCV), genotype (GT) 1, 4 or 6 infection. The primary hypothesis is that the percentage of participants receiving grazoprevir/elbasvir FDC in the Immediate Treatment Group (ITG) achieving Sustained Virologic Response 12 weeks after the end of all study therapy (SVR12) will be superior to the historical reference rate of 73%.

Official Title
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A Phase III Randomized Multinational Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-5172/MK-8742 in Treatment-Naïve Subjects With Chronic HCV GT 1, GT 4 and GT 6 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 documented chronic HCV GT1, GT4, or GT6 (with no evidence of non-typeable or mixed genotype) infection Meets clinical criteria for presence or absence of cirrhosis based on liver disease staging assessment Is abstinent or uses acceptable method(s) of contraception Exclusion Criteria: Has evidence of decompensated liver disease Is coinfected with hepatitis B virus or human immunodeficiency virus (HIV) Shows evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC Has a clinically-relevant drug or alcohol abuse within 12 months of screening Is pregnant or breast-feeding Has any condition or abnormality that might confound the results of the trial or pose an additional risk to the participant

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 Group (ITG): Grazoprevir/Elbasvir<br>Participants receive a grazoprevir/elbasvir FDC tablet once daily (q.d.) by mouth during a 12-week Active Treatment period (Week 1 to Week 12) and are followed-up for 24 weeks to Week 36. | Drug: Grazoprevir/Elbasvir<br>* FDC tablet containing 100 mg of grazoprevir and 50 mg of elbasvir taken q.d. by mouth for 12 weeks.<br>* Other names: MK-5172A;|
| Placebo Comparator: Deferred Treatment Group (DTG): Placebo > Grazoprevir/Elbasvir<br>Participants receive a placebo tablet q.d. by mouth for 12 weeks (placebo treatment period). After a 4-week Follow-Up period, participants receive open-label grazoprevir/elbasvir FDC during a 12-week Active Treatment period (Week 16 to Week 28). Participants are then followed-up for 24 weeks to Week 52. | Drug: Placebo<br>* Placebo tablet matching grazoprevir/elbasvir FDC tablet taken q.d. by mouth for 12 weeks.<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 the End of All Study Therapy (SVR12) | Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS® AmpliPrep/COBAS® Taqman HCV Test, v2.0, which had a lower limit of quantification (LLOQ) of 15 IU/mL. SVR12 was defined as HCV RNA below the lower limit of detection (<LLOQ) at 12 weeks after the end of all study therapy. As pre-specified in the protocol, the Deferred Treatment Group was not included in the primary efficacy analysis. | 12 weeks after end of all therapy (Study Week 24) | 
| Percentage of Participants Experiencing at Least One Adverse Event (AE) During the DB Treatment Period and First 14 Follow-up Days | 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. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that is temporally associated with the use of the Sponsor's product, is also an AE. The primary safety analysis compared the safety data of the Immediate Treatment Group during the active treatment period to those of the Deferred Treatment Group during the placebo treatment period. | DB Treatment period plus first 14 follow-up days (up to 14 weeks) | 
| Percentage of Participants That Discontinued From Study Therapy Due to AEs During the DB Treatment Period | 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. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that is temporally associated with the use of the Sponsor's product, is also an AE. A participant could discontinue from treatment but continue to participate in the study as long as consent was not withdrawn. The primary safety analysis compared the safety data of the Immediate Treatment Group during the active treatment period to those of the Deferred Treatment Group during the placebo treatment period. | DB Treatment period (up to 12 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of All Study Therapy (SVR24) | Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS® AmpliPrep/COBAS® Taqman HCV Test, v2.0, which had a LLOQ of 15 IU/mL. SVR24 was defined as HCV RNA <LLOQ at 24 weeks after the end of all study therapy. As pre-specified in the protocol, the Deferred Treatment Group was not included in the secondary efficacy analysis. | 24 weeks after end of all therapy (Study Week 36) |