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

Brief Summary

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”

This is a study of the safety and efficacy of MK-5172 in combination with 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.

  • Study Type: Interventional
  • Study Design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
  • Study Primary Completion Date: March 2015

Detailed Clinical Trial 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 MK-5172 100 mg once daily (QD) + MK-8742 20 mg or 50 mg QD and twice daily (BID) RBV, or to a treatment arm in which they will receive MK-5172 100 mg QD + MK-8742 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 MK-5172 (100 mg) in combination with MK-8742 (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 MK-5172 (100 mg) in combination with MK-8742 (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 MK-5172 (100 mg) in combination with MK-8742 (50 mg) + RBV for 12 or 18 weeks.

Interventions Used in this Clinical Trial

  • Drug: MK-5172
    • 100 mg tablet orally QD
  • Drug: MK-8742
    • Part A: 20 or 50 mg capsule orally QD Part B: 50 mg capsule orally QD
  • Drug: Placebo
    • Placebo to MK-8742 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

Arms, Groups and Cohorts in this Clinical Trial

  • Experimental: A: TN/N-C MK-5172+MK-8742 20 mg+RBV
    • GT1a and GT1b participants receive MK-5172 100 mg tablet orally QD for 12 weeks, MK-8742 20 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
  • Experimental: A: TN/N-C MK-5172+MK-8742 50 mg+RBV
    • GT1a and GT1b participants receive MK-5172 100 mg tablet orally QD for 12 weeks, MK-8742 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
  • Experimental: A: TN/N-C MK-5172+MK-8742 50 mg
    • GT1b only participants receive MK-5172 100 mg tablet orally QD for 12 weeks, MK-8742 50 mg capsule orally QD for 12 weeks
  • Experimental: B: TN/N-C MK-5172+MK-8742+RBV 8 wk
    • GT1a only participants receive MK-5172 100 mg tablet orally QD for 8 weeks, MK-8742 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
  • Experimental: B: TN/N-C MK-5172+MK-8742+RBV 12 wk
    • GT1a/non-a participants receive MK-5172 100 mg tablet orally QD for 12 weeks, MK-8742 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
  • Experimental: B: TN/N-C MK-5172+MK-8742 12 wk
    • GT1a only participants receive MK-5172 100 mg tablet orally QD for 12 weeks, MK-8742 50 mg capsule orally QD for 12 weeks
  • Experimental: B: TN/C MK-5172+MK-8742+RBV 12 wk
    • GT1a/non-a participants receive MK-5172 100 mg tablet orally QD for 12 weeks, MK-8742 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
  • Experimental: B: TN/C MK-5172+MK-8742 12 wk
    • GT1a/non-a participants receive MK-5172 100 mg tablet orally QD for 12 weeks, MK-8742 50 mg capsule orally QD for 12 weeks
  • Experimental: B: TN/C MK-5172+MK-8742+RBV 18 wk
    • GT1a/non-a participants receive MK-5172 100 mg tablet orally QD for 18 weeks, MK-8742 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
  • Experimental: B: TN/C MK-5172+MK-8742 18 wk
    • GT1a/non-a participants receive MK-5172 100 mg tablet orally QD for 18 weeks, MK-8742 50 mg capsule orally QD for 18 weeks
  • Experimental: B: NR/C/N-C MK-5172+MK-8742+RBV 12 wk
    • GT1a/non-a participants receive MK-5172 100 mg tablet orally QD for 12 weeks, MK-8742 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
  • Experimental: B: NR/C/N-C MK-5172+MK-8742 12 wk
    • GT1a/non-a participants receive MK-5172 100 mg tablet orally QD for 12 weeks, MK-8742 50 mg capsule orally QD for 12 weeks
  • Experimental: B: NR/C/N-C MK-5172+MK-8742+RBV 18 wk
    • GT1a/non-a participants receive MK-5172 100 mg tablet orally QD for 18 weeks, MK-8742 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
  • Experimental: B: NR/C/N-C MK-5172+MK-8742 18 wk
    • GT1a/non-a participants receive MK-5172 100 mg tablet orally QD for 18 weeks, MK-8742 50 mg capsule orally QD for 18 weeks
  • Experimental: B: TN/N-C/HIV MK-5172+MK-8742+RBV 12 wk
    • GT1a/non-a participants receive MK-5172 100 mg tablet orally QD for 12 weeks, MK-8742 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
  • Experimental: B: TN/N-C/HIV MK-5172+MK-8742 12 wk
    • GT1a/non-a participants receive MK-5172 100 mg tablet orally QD for 12 weeks, MK-8742 50 mg capsule orally QD for 12 weeks
  • Experimental: C: TN/N-C MK-5172+MK-8742+RBV 8 wk
    • GT1b participants receive MK-5172 100 mg tablet orally QD for 8 weeks, MK-8742 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.
  • Experimental: C: TN/N-C MK-5172+MK-8742 8wk
    • GT1b participants receive MK-5172 100 mg tablet orally QD for 8 weeks and MK-8742 50 mg capsule orally QD for 8 weeks
  • Experimental: D: TN/N-C MK-5172+MK-8742+RBV 12 wk
    • GT3 participants receive MK-5172 100 mg tablet orally QD for 12 weeks, MK-8742 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
  • Experimental: D: TN/N-C MK-5172+MK-8742+RBV 18 wk
    • GT3 participants receive MK-5172 100 mg tablet orally QD for 18 weeks, MK-8742 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

Outcome Measures for this Clinical Trial

Primary Measures

  • Number of participants achieving Sustained Virologic Response 12 weeks after the end of all study therapy (SVR12)
    • Time Frame: Up to 30 weeks
      Safety Issue?: No
  • Number of participants experiencing at least one Adverse Event (AE) on study
    • Time Frame: Up to 42 weeks
      Safety Issue?: Yes
  • Number of participants discontinuing study therapy due to an AE
    • Time Frame: Up to 18 weeks
      Safety Issue?: Yes

Secondary Measures

  • Time to first achievement of undetectable hepatitis C virus ribonucleic acid (HCV RNA)
    • Time Frame: Up to 18 weeks
      Safety Issue?: No
  • Number of participants achieving undetectable HCV RNA at Week 2
    • Time Frame: Week 2
      Safety Issue?: No
  • Number of participants achieving undetectable HCV RNA at Week 4
    • Time Frame: Week 4
      Safety Issue?: No
  • Number of participants achieving undetectable HCV RNA at Week 12
    • Time Frame: Week 12
      Safety Issue?: No
  • Number of participants achieving HCV RNA <25 IU/mL at Week 2
    • Time Frame: Week 2
      Safety Issue?: No
  • Number of participants achieving HCV RNA <25 IU/mL at Week 4
    • Time Frame: Week 4
      Safety Issue?: No
  • Number of participants achieving HCV RNA <25 IU/mL at Week 12
    • Time Frame: Week 12
      Safety Issue?: No
  • Number of participants achieving End-Of-Treatment Response (EOTR)
    • Time Frame: Up to 18 weeks
      Safety Issue?: No
  • Number of participants achieving Sustained Virologic Response 4 weeks after the end of all therapy (SVR4)
    • Time Frame: Up to 22 weeks
      Safety Issue?: No
  • Number of participants achieving Sustained Virologic Response 24 weeks after the end of all study therapy (SVR24)
    • Time Frame: Up to 42 weeks
      Safety Issue?: No

Criteria for Participation in this Clinical Trial

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%

    Gender Eligibility for this Clinical Trial: Both

    Minimum Age for this Clinical Trial: 18 Years

    Maximum Age for this Clinical Trial: N/A

    Are Healthy Volunteers Accepted for this Clinical Trial: No

    Clinical Trial Investigator Information

    • Lead Sponsor
      • Merck Sharp & Dohme Corp.
    • Provider of Information About this Clinical Study
      • Sponsor

    Source

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    The URL of this page is:
    http://clinicaltrialsfeeds.org/clinical-trials/show/NCT01717326