A Study of the Combination Regimen Grazoprevir (MK-5172) and Elbasvir (MK-8742) ± Ribavirin in Participants With Chronic Hepatitis C (MK-5172-035) (C-WORTHy)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01717326
First received: October 26, 2012
Last updated: April 21, 2016
Last verified: April 2016
  Purpose
This is a study of the safety and efficacy of grazoprevir (MK-5172) in combination with elbasvir (MK-8742) ± ribavirin (RBV). The primary efficacy endpoint will be Sustained Virologic Response 12 weeks after the end of all study therapy (SVR12) in each of the treatment arms.

Condition Intervention Phase
Hepatitis C
Drug: Grazoprevir
Drug: Elbasvir
Drug: Placebo to Elbasvir
Drug: Ribavirin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase II Randomized Clinical Trial to Study the Efficacy and Safety of the Combination Regimen MK-5172 and MK-8742 ± Ribavirin (RBV) in Subjects With Chronic Hepatitis C Virus Infection

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of All Study Therapy (SVR12) [ Time Frame: 12 weeks after end of therapy (up to 30 weeks) ] [ Designated as safety issue: No ]
    Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a lower limit of quantification of 25 IU/mL and a limit of detection of 15.1 IU/mL (in plasma). SVR12 was defined as HCV RNA <25 IU/ml at 12 weeks after the end of all study therapy. 95% confidence intervals provided based on the Clopper-Pearson method.

  • Percentage of Participants Experiencing at Least One Adverse Event (AE) During the Treatment Period and First 14 Follow-up Days [ Time Frame: From Day 1 [post-dose] through 14 days following last dose of study drug (up to 20 weeks) ] [ Designated as safety issue: Yes ]
    An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), 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 (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product, was also an AE.

  • Percentage of Participants Discontinuing Study Therapy Due to an AE During the Treatment Period and First 14 Follow-up Days [ Time Frame: From Day 1 [post-dose] through 14 days following last dose of study drug (up to 20 weeks) ] [ Designated as safety issue: Yes ]
    An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), 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 (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product, was also an AE.


Secondary Outcome Measures:
  • Mean Time to First Achievement of Undetectable Hepatitis C Virus Ribonucleic Acid (HCV RNA) [ Time Frame: From first dose of study medication until first achievement of undetectable HCV RNA (up to 18 weeks of treatment) ] [ Designated as safety issue: No ]
    Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 at various time points prior to, during, and after dosing. Kaplan Meier summary statistics were used to characterize the time to first achievement of undetectable HCV RNA.

  • Percentage of Participants Achieving Undetectable HCV RNA at Week 2 [ Time Frame: Week 2 ] [ Designated as safety issue: No ]
    HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at various time points prior to, during, and after dosing. Undetectable HCV RNA was defined as below the 15.1 IU/ml limit of detection. The percentage of participants achieving undetectable HCV RNA and accompanying 95% CIs were reported at TW2 for each treatment arm of the PP Population. 95% confidence intervals provided based on the Clopper-Pearson method.

  • Percentage of Participants Achieving Undetectable HCV RNA at Week 4 [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at various time points prior to, during, and after dosing. Undetectable HCV RNA was defined as below the 15.1 IU/ml limit of detection. The percentage of participants achieving undetectable HCV RNA and accompanying 95% CIs were reported at TW4 for each treatment arm of the PP Population. 95% confidence intervals provided based on the Clopper-Pearson method.

  • Percentage of Participants Achieving Undetectable HCV RNA at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at various time points prior to, during, and after dosing. Undetectable HCV RNA was defined as below the 15.1 IU/ml limit of detection. The percentage of participants achieving undetectable HCV RNA and accompanying 95% CIs were reported at TW12 for each treatment arm of the PP Population (as applicable). 95% confidence intervals provided based on the Clopper-Pearson method.

  • Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 2 [ Time Frame: Week 2 ] [ Designated as safety issue: No ]
    HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a LLoQ of 25 IU/mL and a limit of detection of 15.1 IU/mL (in plasma). The percentage of participants achieving HCV RNA levels <25 IU/ml and accompanying 95% CIs were reported at TW2 for each treatment arm of the PP Population. 95% confidence intervals provided based on the Clopper-Pearson method.

  • Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 4 [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a LLoQ of 25 IU/mL and a limit of detection of 15.1 IU/mL (in plasma). The percentage of participants achieving HCV RNA levels <25 IU/ml and accompanying 95% CIs were reported at TW4 for each treatment arm of the PP Population. 95% confidence intervals provided based on the Clopper-Pearson method.

  • Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a LLoQ of 25 IU/mL and a limit of detection of 15.1 IU/mL (in plasma). The percentage of participants achieving HCV RNA levels <25 IU/ml and accompanying 95% CIs were reported at TW12 for each treatment arm of the PP Population (as applicable). 95% confidence intervals provided based on the Clopper-Pearson method.

  • Percentage of Participants Achieving Sustained Virologic Response 4 Weeks After the End of All Therapy (SVR4) [ Time Frame: 4 weeks after end of therapy (up to 22 weeks) ] [ Designated as safety issue: No ]
    Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a LLoQ of 25 IU/mL and a limit of detection of 15.1 IU/mL (in plasma). SVR4 was defined as HCV RNA <25 IU/ml at 4 weeks after the end of all study therapy. 95% confidence intervals provided based on the Clopper-Pearson method.

  • Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of All Study Therapy (SVR24) [ Time Frame: 24 weeks after end of therapy (up to 42 weeks) ] [ Designated as safety issue: No ]
    Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS™ Taqman™ HCV Test, v2.0 at various time points prior to, during, and after dosing. The Roche COBAS Taqman HCV Test, v2.0 assay (High Pure System) had a LLoQ of 25 IU/mL and a limit of detection of 15.1 IU/mL (in plasma). SVR24 was defined as HCV RNA <25 IU/ml at 24 weeks after the end of all study therapy. 95% confidence intervals provided based on the Clopper-Pearson method.


Enrollment: 573
Study Start Date: February 2013
Study Completion Date: May 2015
Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A1: TN NC Grazoprevir 100 mg + Elbasvir 20 mg + RBV-12 wk
GT1a and GT1b participants receive Grazoprevir 100 mg tablet orally once daily (QD) for 12 weeks, Elbasvir 20 mg capsule and Placebo capsule orally QD for 12 weeks, RBV capsules orally twice daily (BID) for 24 weeks at a total daily dose from 800 to 1400 mg based on participant weight
Drug: Grazoprevir
100 mg tablet orally QD
Other Name: MK-5172
Drug: Elbasvir
Part A: 20 or 50 mg capsule orally QD Parts B, C, and D: 50 mg capsule orally QD
Other Name: MK-8742
Drug: Placebo to Elbasvir
Placebo to Elbasvir 20 or 50 mg capsule, orally, once daily for 12 weeks to maintain blind (Part A only)
Drug: Ribavirin
Oral capsules BID at a total daily dose from 800 to 1400 mg based on participant weight
Other Names:
  • Rebetol™
  • RBV
Experimental: A2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk
GT1a and GT1b participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule and Placebo capsule orally QD for 12 weeks, RBV capsules orally BID for 24 weeks at a total daily dose from 800 to 1400 mg based on participant weight
Drug: Grazoprevir
100 mg tablet orally QD
Other Name: MK-5172
Drug: Elbasvir
Part A: 20 or 50 mg capsule orally QD Parts B, C, and D: 50 mg capsule orally QD
Other Name: MK-8742
Drug: Placebo to Elbasvir
Placebo to Elbasvir 20 or 50 mg capsule, orally, once daily for 12 weeks to maintain blind (Part A only)
Drug: Ribavirin
Oral capsules BID at a total daily dose from 800 to 1400 mg based on participant weight
Other Names:
  • Rebetol™
  • RBV
Experimental: A3: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg-12 wk
GT1b only participants receive Grazoprevr 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks
Drug: Grazoprevir
100 mg tablet orally QD
Other Name: MK-5172
Drug: Elbasvir
Part A: 20 or 50 mg capsule orally QD Parts B, C, and D: 50 mg capsule orally QD
Other Name: MK-8742
Experimental: B1: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk
GT1a only participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight
Drug: Grazoprevir
100 mg tablet orally QD
Other Name: MK-5172
Drug: Elbasvir
Part A: 20 or 50 mg capsule orally QD Parts B, C, and D: 50 mg capsule orally QD
Other Name: MK-8742
Drug: Ribavirin
Oral capsules BID at a total daily dose from 800 to 1400 mg based on participant weight
Other Names:
  • Rebetol™
  • RBV
Experimental: B2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk
GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight
Drug: Grazoprevir
100 mg tablet orally QD
Other Name: MK-5172
Drug: Elbasvir
Part A: 20 or 50 mg capsule orally QD Parts B, C, and D: 50 mg capsule orally QD
Other Name: MK-8742
Drug: Ribavirin
Oral capsules BID at a total daily dose from 800 to 1400 mg based on participant weight
Other Names:
  • Rebetol™
  • RBV
Experimental: B3: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 mg-12 wk
GT1a only participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks
Drug: Grazoprevir
100 mg tablet orally QD
Other Name: MK-5172
Drug: Elbasvir
Part A: 20 or 50 mg capsule orally QD Parts B, C, and D: 50 mg capsule orally QD
Other Name: MK-8742
Experimental: B4: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk
GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant
Drug: Grazoprevir
100 mg tablet orally QD
Other Name: MK-5172
Drug: Elbasvir
Part A: 20 or 50 mg capsule orally QD Parts B, C, and D: 50 mg capsule orally QD
Other Name: MK-8742
Drug: Ribavirin
Oral capsules BID at a total daily dose from 800 to 1400 mg based on participant weight
Other Names:
  • Rebetol™
  • RBV
Experimental: B5: TN C Grazoprevir 100 mg + Elbasvir 50 mg for 12 wk
GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks
Drug: Grazoprevir
100 mg tablet orally QD
Other Name: MK-5172
Drug: Elbasvir
Part A: 20 or 50 mg capsule orally QD Parts B, C, and D: 50 mg capsule orally QD
Other Name: MK-8742
Experimental: B6: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk
GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks, RBV capsules orally BID for 18 weeks at a total daily dose from 800 to 1400 mg based on participant weight
Drug: Grazoprevir
100 mg tablet orally QD
Other Name: MK-5172
Drug: Elbasvir
Part A: 20 or 50 mg capsule orally QD Parts B, C, and D: 50 mg capsule orally QD
Other Name: MK-8742
Drug: Ribavirin
Oral capsules BID at a total daily dose from 800 to 1400 mg based on participant weight
Other Names:
  • Rebetol™
  • RBV
Experimental: B7: TN C Grazoprevir 100 mg + Elbasvir 50 mg-18 wk
GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks
Drug: Grazoprevir
100 mg tablet orally QD
Other Name: MK-5172
Drug: Elbasvir
Part A: 20 or 50 mg capsule orally QD Parts B, C, and D: 50 mg capsule orally QD
Other Name: MK-8742
Experimental: B8: NR Grazoprevir 100 mg + Elbasvir 50 mg +RBV-12 wk
GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight
Drug: Grazoprevir
100 mg tablet orally QD
Other Name: MK-5172
Drug: Elbasvir
Part A: 20 or 50 mg capsule orally QD Parts B, C, and D: 50 mg capsule orally QD
Other Name: MK-8742
Drug: Ribavirin
Oral capsules BID at a total daily dose from 800 to 1400 mg based on participant weight
Other Names:
  • Rebetol™
  • RBV
Experimental: B9: NR Grazoprevir 100 mg + Elbasvir 50 mg-12 wk
GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks
Drug: Grazoprevir
100 mg tablet orally QD
Other Name: MK-5172
Drug: Elbasvir
Part A: 20 or 50 mg capsule orally QD Parts B, C, and D: 50 mg capsule orally QD
Other Name: MK-8742
Experimental: B10: NR Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk
GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks, RBV capsules orally BID for 18 weeks at a total daily dose from 800 to 1400 mg based on participant weight
Drug: Grazoprevir
100 mg tablet orally QD
Other Name: MK-5172
Drug: Elbasvir
Part A: 20 or 50 mg capsule orally QD Parts B, C, and D: 50 mg capsule orally QD
Other Name: MK-8742
Drug: Ribavirin
Oral capsules BID at a total daily dose from 800 to 1400 mg based on participant weight
Other Names:
  • Rebetol™
  • RBV
Experimental: B11: NR Grazoprevir 100 mg + Elbasvir 50 mg-18 wk
GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks
Drug: Grazoprevir
100 mg tablet orally QD
Other Name: MK-5172
Drug: Elbasvir
Part A: 20 or 50 mg capsule orally QD Parts B, C, and D: 50 mg capsule orally QD
Other Name: MK-8742
Experimental: B12: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk
GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight
Drug: Grazoprevir
100 mg tablet orally QD
Other Name: MK-5172
Drug: Elbasvir
Part A: 20 or 50 mg capsule orally QD Parts B, C, and D: 50 mg capsule orally QD
Other Name: MK-8742
Drug: Ribavirin
Oral capsules BID at a total daily dose from 800 to 1400 mg based on participant weight
Other Names:
  • Rebetol™
  • RBV
Experimental: B13: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 mg-12 wk
GT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks
Drug: Grazoprevir
100 mg tablet orally QD
Other Name: MK-5172
Drug: Elbasvir
Part A: 20 or 50 mg capsule orally QD Parts B, C, and D: 50 mg capsule orally QD
Other Name: MK-8742
Experimental: C1: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk
GT1b participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks, Elbasvir 50 mg capsule orally QD for 8 weeks, and RBV capsules orally BID for 8 weeks at a total daily dose from 800 to 1400 mg based on participant weight.
Drug: Grazoprevir
100 mg tablet orally QD
Other Name: MK-5172
Drug: Elbasvir
Part A: 20 or 50 mg capsule orally QD Parts B, C, and D: 50 mg capsule orally QD
Other Name: MK-8742
Drug: Ribavirin
Oral capsules BID at a total daily dose from 800 to 1400 mg based on participant weight
Other Names:
  • Rebetol™
  • RBV
Experimental: C2: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg-8 wk
GT1b participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks and Elbasvir 50 mg capsule orally QD for 8 weeks
Drug: Grazoprevir
100 mg tablet orally QD
Other Name: MK-5172
Drug: Elbasvir
Part A: 20 or 50 mg capsule orally QD Parts B, C, and D: 50 mg capsule orally QD
Other Name: MK-8742
Experimental: D1: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk
GT3 participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks, and RBV capsules orally BID for 12 weeks at a total daily dose from 800 to 1400 mg based on participant weight
Drug: Grazoprevir
100 mg tablet orally QD
Other Name: MK-5172
Drug: Elbasvir
Part A: 20 or 50 mg capsule orally QD Parts B, C, and D: 50 mg capsule orally QD
Other Name: MK-8742
Drug: Ribavirin
Oral capsules BID at a total daily dose from 800 to 1400 mg based on participant weight
Other Names:
  • Rebetol™
  • RBV
Experimental: D2: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk
GT3 participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks, and RBV capsules orally BID for 18 weeks at a total daily dose from 800 to 1400 mg based on participant weight
Drug: Grazoprevir
100 mg tablet orally QD
Other Name: MK-5172
Drug: Elbasvir
Part A: 20 or 50 mg capsule orally QD Parts B, C, and D: 50 mg capsule orally QD
Other Name: MK-8742
Drug: Ribavirin
Oral capsules BID at a total daily dose from 800 to 1400 mg based on participant weight
Other Names:
  • Rebetol™
  • RBV

Detailed Description:

Part A is being done in treatment-naïve (TN), genotype 1 (GT1), interferon eligible, non-cirrhotic (N-C) participants with chronic hepatitis C (CHC). Participants will be assigned randomly to 1 of 2 treatment arms in which they will receive grazoprevir 100 mg once daily (QD) + elbasvir 20 mg or 50 mg QD and twice daily (BID) RBV, or to a treatment arm in which they will receive grazoprevir 100 mg QD + elbasvir 50 mg QD without RBV. Treatment will last 12 weeks.

In Part B, participants with hepatitis C virus (HCV) GT1 and HCV ribonucleic acid (RNA) levels of ≥10,000 IU/mL will be randomly assigned to a study arm, based on absence or presence of cirrhosis (C), whether they are TN or had poor response to previous antiviral therapy (null responders [NR]), or whether co-infected with human immunodeficiency virus (HIV); these participants will receive open-label grazoprevir (100 mg) in combination with elbasvir (50 mg) ± RBV. Treatment will last 8 to 18 weeks dependent on arm assignment.

In Part C, TN, N-C participants with HCV GT1b and HCV RNA levels of ≥10,000 IU/mL will be randomly assigned to receive open-label grazoprevir (100 mg) in combination with elbasvir (50 mg) ± RBV. Treatment will last 8 weeks.

In Part D, TN N-C participants with HCV GT3 and HCV RNA levels of ≥10,000 IU/mL will be randomly assigned to receive open-label grazoprevir (100 mg) in combination with elbasvir (50 mg) + RBV for 12 or 18 weeks.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

All participants

  • CHC genotype 1 (GT1) virus infection (Parts A, B, and C) or GT3 virus infection (Part D)
  • Female participants of childbearing potential or male participant with female partners of childbearing potential, must use two acceptable methods of birth control from ≥2 weeks prior to Day 1 until ≥6 months after last dose of study drug, or longer if dictated by local regulations

Part A - Absence (no medical history or physical findings) of ascites, bleeding esophageal varices, hepatic encephalopathy, or other signs or symptoms of advanced liver disease, or cirrhosis - No evidence of advanced fibrosis, cirrhosis and/or hepatocellular carcinoma by biopsy or noninvasive testing (FibroScan and/or FibroTest)

Parts B, C, and D

  • Treatment naïve with or without cirrhosis, or
  • Prior treatment failure to Peg-IFN/Ribavirin with or without cirrhosis, or
  • Co-infected with human immunodeficiency virus (HIV) without cirrhosis
  • Absence (no medical history or physical findings) of ascites, bleeding esophageal varices, hepatic encephalopathy, or other signs or symptoms of advanced liver disease
  • Liver disease staging assessment by liver biopsy or noninvasive testing (FibroScan and/or FibroTest)

Exclusion criteria:

All participants

  • Non-GT1 HCV infection (Part A, Part B, and Part C) or a non-GT3 HCV infection (Part D) including a mixed GT infection (with a non-GT1 [Part A, Part B, and Part C] or non-GT3 [Part D]) or a non-typeable genotype
  • Evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC
  • Currently participating or 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 study
  • Diabetic and/or hypertensive with clinically significant ocular examination findings
  • History of depression associated with hospitalization for depression, electroconvulsive therapy, or resulting in prolonged absence from work and/or significant disruption of daily functions
  • Suicidal or homicidal ideations and/or attempt, or history of severe psychiatric disorders
  • Clinical diagnosis of substance abuse
  • Current history of seizure disorder, stroke, or transient ischemic attack
  • Immunologically mediated disease
  • Chronic pulmonary disease
  • Clinically significant cardiac abnormalities/dysfunction
  • Active clinical gout within the last year
  • Hemoglobinopathy or myelodysplastic syndromes
  • History of organ transplants including hematopoietic stem cell transplants
  • Poor venous access
  • Indwelling venous catheter
  • History of gastric surgery or malabsorption disorders
  • Severe concurrent disease
  • Evidence of active or suspected malignancy, or a history of malignancy, ≤5 years before
  • Pregnant, lactating, expecting to conceive or donate eggs
  • Male participant with pregnant female partner
  • Member/family member of the investigational study or sponsor staff directly involved with this study
  • Evidence or history of chronic hepatitis not caused by HCV

Part A

  • Not treatment-naïve
  • Documented to be HIV positive
  • Taking or planning to take significant inducers or inhibitors of CYP3A4 substrates or herbal supplements 2 weeks prior to start of study medications

Parts B, C, and D

  • Previously received any HCV direct-acting antivirals
  • Requiring, or likely to require, chronic systemic administration of corticosteroids during the course of the trial
  • For participants diagnosed with diabetes mellitus, documented HbA1c >8.5%
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

Publications:
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01717326     History of Changes
Other Study ID Numbers: 5172-035  2012-003354-89 
Study First Received: October 26, 2012
Results First Received: February 16, 2016
Last Updated: April 21, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis, Chronic
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Ribavirin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on July 24, 2016