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
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
2 other identifiers
interventional
573
0 countries
N/A
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Feb 2013
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 26, 2012
CompletedFirst Posted
Study publicly available on registry
October 30, 2012
CompletedStudy Start
First participant enrolled
February 7, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 23, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
May 6, 2015
CompletedResults Posted
Study results publicly available
May 30, 2016
CompletedFebruary 5, 2021
January 1, 2021
2 years
October 26, 2012
February 16, 2016
January 15, 2021
Conditions
Outcome Measures
Primary Outcomes (3)
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™ 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.
12 weeks after end of therapy (up to 30 weeks)
Percentage of Participants Experiencing at Least One Adverse Event (AE) During the Treatment Period and First 14 Follow-up Days
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.
From Day 1 [post-dose] through 14 days following last dose of study drug (up to 20 weeks)
Percentage of Participants Discontinuing Study Therapy Due to an AE During the Treatment Period and First 14 Follow-up Days
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.
From Day 1 [post-dose] through 14 days following last dose of study drug (up to 20 weeks)
Secondary Outcomes (9)
Mean Time to First Achievement of Undetectable Hepatitis C Virus Ribonucleic Acid (HCV RNA)
From first dose of study medication until first achievement of undetectable HCV RNA (up to 18 weeks of treatment)
Percentage of Participants Achieving Undetectable HCV RNA at Week 2
Week 2
Percentage of Participants Achieving Undetectable HCV RNA at Week 4
Week 4
Percentage of Participants Achieving Undetectable HCV RNA at Week 12
Week 12
Percentage of Participants Achieving HCV RNA <25 IU/mL at Week 2
Week 2
- +4 more secondary outcomes
Study Arms (20)
A1: TN NC Grazoprevir 100 mg + Elbasvir 20 mg + RBV-12 wk
EXPERIMENTALGT1a 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
A2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk
EXPERIMENTALGT1a 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
A3: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg-12 wk
EXPERIMENTALGT1b only participants receive Grazoprevr 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks
B1: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk
EXPERIMENTALGT1a 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
B2: TN NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk
EXPERIMENTALGT1a/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
B3: TN NC/GT1a Grazoprevir 100 mg + Elbasvir 50 mg-12 wk
EXPERIMENTALGT1a only participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks
B4: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk
EXPERIMENTALGT1a/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
B5: TN C Grazoprevir 100 mg + Elbasvir 50 mg for 12 wk
EXPERIMENTALGT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks
B6: TN C Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk
EXPERIMENTALGT1a/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
B7: TN C Grazoprevir 100 mg + Elbasvir 50 mg-18 wk
EXPERIMENTALGT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks
B8: NR Grazoprevir 100 mg + Elbasvir 50 mg +RBV-12 wk
EXPERIMENTALGT1a/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
B9: NR Grazoprevir 100 mg + Elbasvir 50 mg-12 wk
EXPERIMENTALGT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks
B10: NR Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk
EXPERIMENTALGT1a/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
B11: NR Grazoprevir 100 mg + Elbasvir 50 mg-18 wk
EXPERIMENTALGT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 18 weeks, Elbasvir 50 mg capsule orally QD for 18 weeks
B12: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk
EXPERIMENTALGT1a/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
B13: TN HIV NC Grazoprevir 100 mg + Elbasvir 50 mg-12 wk
EXPERIMENTALGT1a/non-a participants receive Grazoprevir 100 mg tablet orally QD for 12 weeks, Elbasvir 50 mg capsule orally QD for 12 weeks
C1: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg + RBV-8 wk
EXPERIMENTALGT1b 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.
C2: TN NC/GT1b Grazoprevir 100 mg + Elbasvir 50 mg-8 wk
EXPERIMENTALGT1b participants receive Grazoprevir 100 mg tablet orally QD for 8 weeks and Elbasvir 50 mg capsule orally QD for 8 weeks
D1: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-12 wk
EXPERIMENTALGT3 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
D2: TN NC/GT3 Grazoprevir 100 mg + Elbasvir 50 mg + RBV-18 wk
EXPERIMENTALGT3 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
Interventions
100 mg tablet orally QD
Part A: 20 or 50 mg capsule orally QD Parts B, C, and D: 50 mg capsule orally QD
Placebo to Elbasvir 20 or 50 mg capsule, orally, once daily for 12 weeks to maintain blind (Part A only)
Oral capsules BID at a total daily dose from 800 to 1400 mg based on participant weight
Eligibility Criteria
You may qualify if:
- 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)
You may not qualify if:
- 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
- +17 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Related Publications (4)
Lawitz E, Gane E, Pearlman B, Tam E, Ghesquiere W, Guyader D, Alric L, Bronowicki JP, Lester L, Sievert W, Ghalib R, Balart L, Sund F, Lagging M, Dutko F, Shaughnessy M, Hwang P, Howe AY, Wahl J, Robertson M, Barr E, Haber B. Efficacy and safety of 12 weeks versus 18 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin for hepatitis C virus genotype 1 infection in previously untreated patients with cirrhosis and patients with previous null response with or without cirrhosis (C-WORTHY): a randomised, open-label phase 2 trial. Lancet. 2015 Mar 21;385(9973):1075-86. doi: 10.1016/S0140-6736(14)61795-5. Epub 2014 Nov 11.
PMID: 25467591BACKGROUNDSulkowski M, Hezode C, Gerstoft J, Vierling JM, Mallolas J, Pol S, Kugelmas M, Murillo A, Weis N, Nahass R, Shibolet O, Serfaty L, Bourliere M, DeJesus E, Zuckerman E, Dutko F, Shaughnessy M, Hwang P, Howe AY, Wahl J, Robertson M, Barr E, Haber B. Efficacy and safety of 8 weeks versus 12 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin in patients with hepatitis C virus genotype 1 mono-infection and HIV/hepatitis C virus co-infection (C-WORTHY): a randomised, open-label phase 2 trial. Lancet. 2015 Mar 21;385(9973):1087-97. doi: 10.1016/S0140-6736(14)61793-1. Epub 2014 Nov 11.
PMID: 25467560BACKGROUNDGane E, Nahass R, Luketic V, Asante-Appiah E, Hwang P, Robertson M, Wahl J, Barr E, Haber B. Efficacy of 12 or 18 weeks of elbasvir plus grazoprevir with ribavirin in treatment-naive, noncirrhotic HCV genotype 3-infected patients. J Viral Hepat. 2017 Oct;24(10):895-899. doi: 10.1111/jvh.12719. Epub 2017 Jun 23.
PMID: 28470815DERIVEDJacobson IM, Lawitz E, Kwo PY, Hezode C, Peng CY, Howe AYM, Hwang P, Wahl J, Robertson M, Barr E, Haber BA. Safety and Efficacy of Elbasvir/Grazoprevir in Patients With Hepatitis C Virus Infection and Compensated Cirrhosis: An Integrated Analysis. Gastroenterology. 2017 May;152(6):1372-1382.e2. doi: 10.1053/j.gastro.2017.01.050. Epub 2017 Feb 11.
PMID: 28193518DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Results Point of Contact* Name or Official Title Senior Vice President, Global Clinical Development
- Organization
- Merck Sharp & Dohme Corp.
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 26, 2012
First Posted
October 30, 2012
Study Start
February 7, 2013
Primary Completion
February 23, 2015
Study Completion
May 6, 2015
Last Updated
February 5, 2021
Results First Posted
May 30, 2016
Record last verified: 2021-01
Data Sharing
- IPD Sharing
- Will share
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf