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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01717326
First received: October 26, 2012
Last updated: October 17, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention Phase
Hepatitis C
Drug: MK-5172
Drug: MK-8742
Drug: Placebo
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:
  • Number of participants achieving Sustained Virologic Response 12 weeks after the end of all study therapy (SVR12) [ Time Frame: Up to 30 weeks ] [ Designated as safety issue: No ]
  • Number of participants experiencing at least one Adverse Event (AE) on study [ Time Frame: Up to 42 weeks ] [ Designated as safety issue: Yes ]
  • Number of participants discontinuing study therapy due to an AE [ Time Frame: Up to 18 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Time to first achievement of undetectable hepatitis C virus ribonucleic acid (HCV RNA) [ Time Frame: Up to 18 weeks ] [ Designated as safety issue: No ]
  • Number of participants achieving undetectable HCV RNA at Week 2 [ Time Frame: Week 2 ] [ Designated as safety issue: No ]
  • Number of participants achieving undetectable HCV RNA at Week 4 [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
  • Number of participants achieving undetectable HCV RNA at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Number of participants achieving HCV RNA <25 IU/mL at Week 2 [ Time Frame: Week 2 ] [ Designated as safety issue: No ]
  • Number of participants achieving HCV RNA <25 IU/mL at Week 4 [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
  • Number of participants achieving HCV RNA <25 IU/mL at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Number of participants achieving End-Of-Treatment Response (EOTR) [ Time Frame: Up to 18 weeks ] [ Designated as 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 ] [ Designated as 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 610
Study Start Date: February 2013
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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
Other Names:
  • Rebetol™
  • RBV
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
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
Other Names:
  • Rebetol™
  • RBV
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
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
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
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: Ribavirin
Oral capsules BID at a total daily dose from 800 to 1400 mg based on participant weight
Other Names:
  • Rebetol™
  • RBV
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
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: Ribavirin
Oral capsules BID at a total daily dose from 800 to 1400 mg based on participant weight
Other Names:
  • Rebetol™
  • RBV
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
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
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
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: Ribavirin
Oral capsules BID at a total daily dose from 800 to 1400 mg based on participant weight
Other Names:
  • Rebetol™
  • RBV
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
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
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
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: Ribavirin
Oral capsules BID at a total daily dose from 800 to 1400 mg based on participant weight
Other Names:
  • Rebetol™
  • RBV
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
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
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
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: Ribavirin
Oral capsules BID at a total daily dose from 800 to 1400 mg based on participant weight
Other Names:
  • Rebetol™
  • RBV
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
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
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
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: Ribavirin
Oral capsules BID at a total daily dose from 800 to 1400 mg based on participant weight
Other Names:
  • Rebetol™
  • RBV
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
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
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
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: Ribavirin
Oral capsules BID at a total daily dose from 800 to 1400 mg based on participant weight
Other Names:
  • Rebetol™
  • RBV
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
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
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.
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: Ribavirin
Oral capsules BID at a total daily dose from 800 to 1400 mg based on participant weight
Other Names:
  • Rebetol™
  • RBV
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
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
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
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: Ribavirin
Oral capsules BID at a total daily dose from 800 to 1400 mg based on participant weight
Other Names:
  • Rebetol™
  • RBV
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
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: 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 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
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

No publications provided

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
Last Updated: October 17, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on October 23, 2014