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
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 489
- Primary Endpoint
- Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of All Study Therapy (SVR12)
Study Overview
Brief Summary
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achieving Sustained Virologic Response 12 weeks after the end of all study therapy (SVR12) will be superior to the historical reference rate of 73%.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Immediate Treatment Group (ITG): Grazoprevir/Elbasvir
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.
Intervention: Grazoprevir/Elbasvir (Drug)
Deferred Treatment Group (DTG): Placebo > Grazoprevir/Elbasvir
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.
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of All Study Therapy (SVR12)
Time Frame: 12 weeks after end of all therapy (Study Week 24)
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.
Percentage of Participants Experiencing at Least One Adverse Event (AE) During the DB Treatment Period and First 14 Follow-up Days
Time Frame: DB Treatment period plus first 14 follow-up days (up to 14 weeks)
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.
Percentage of Participants That Discontinued From Study Therapy Due to AEs During the DB Treatment Period
Time Frame: DB Treatment period (up to 12 weeks)
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.
Secondary Outcomes
- Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of All Study Therapy (SVR24)(24 weeks after end of all therapy (Study Week 36))