Grazoprevir (MK-5172) and Elbasvir (MK-8742) Combination for Chronic Hepatitis C Virus (HCV) Genotypes 1, 4, and 6 (MK-5172-065)

• ClinicalTrials.gov Identifier: NCT02252016
• Recruitment Status: Completed
• First Posted: September 29, 2014
• Results First Posted: January 19, 2017
• Last Update Posted: October 3, 2018
• Sponsor: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

Tracking Information

• First Submitted Date: September 25, 2014
• First Posted Date: September 29, 2014
• Results First Submitted Date: November 22, 2016
• Results First Posted Date: January 19, 2017
• Last Update Posted Date: October 3, 2018
• Actual Study Start Date: October 22, 2014
• Actual Primary Completion Date: December 7, 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 25, 2017)

• Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After Completing Study Therapy (SVR12) [ Time Frame: 12 weeks after completing study therapy (Week 24) ]
  The percentage of participants in the both arms achieving SVR12 (i.e., HCV riboncleic acid [RNA] level below the lower limit of quantification [LLoQ] 12 weeks after completing study therapy) was determined. HCV RNA levels were measured using the Roche COBAS™ Taqman™ HCV Test v2.0 (High Pure System), which has a LLoQ of <15 IU/mL.
• Percentage of Participants Experiencing an Adverse Event (AE) [ Time Frame: Up to Week 14 ]
  An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment.
• Percentage of Participants Discontinuing From Study Treatment Due to an AE(s) [ Time Frame: Up to Week 12 ]
  An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment.

Original Primary Outcome Measures (submitted: September 25, 2014)

• Proportion of participants achieving SVR12 [ Time Frame: Week 24 ]
• Number of participants experiencing an adverse event (AE) [ Time Frame: Up to Week 52 ]
• Number of participants discontinuing from study treatment due to AEs [ Time Frame: Up to Week 12 ]

Current Secondary Outcome Measures (submitted: April 12, 2017)

Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Completing Study Therapy (SVR24) [ Time Frame: 24 weeks after completing study therapy (Week 36) ]

The percentage of participants in both arms achieving SVR24 (i.e., HCV RNA level below the LLoQ 24 weeks after completing study therapy) was determined. HCV RNA levels were measured using the Roche COBAS™ Taqman™ HCV Test v2.0 (High Pure System), which has a LLoQ of <15 IU/mL.

• Original Secondary Outcome Measures (submitted: September 25, 2014): Proportion of subjects achieving SVR24 [ Time Frame: Week 36 ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Grazoprevir (MK-5172) and Elbasvir (MK-8742) Combination for Chronic Hepatitis C Virus (HCV) Genotypes 1, 4, and 6 (MK-5172-065)
• Official Title: A Phase III Double Blind Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-5172 and MK-8742 in Subjects With Chronic HCV GT1, GT4 and GT6 Infection With Inherited Blood Disorders With and Without HIV Co-Infection
• Brief Summary: This is a randomized, multi-site, placebo-controlled trial of a fixed dose combination (FDC) of grazoprevir (MK-5172) 100 mg + elbasvir (MK-8742) 50 mg in participants with chronic Hepatitis C Virus (HCV) genotype (GT) 1, GT4 or GT6 with inherited blood disorders. The primary hypothesis is that the proportion of participants treated with grazoprevir+elbasvir achieving Sustained Virologic Response (SVR) 12 weeks after the end of all study therapy (SVR12) will be greater than the reference rate of 40%.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Hepatitis C

Intervention

• Drug: Grazoprevir + Elbasvir
  FDC tablet containing grazoprevir 100 mg + elbasvir 50 mg taken once daily by mouth.
• Drug: Placebo
  Placebo tablets matching grazoprevir + elbasvir FDC tablets taken once daily by mouth.

Study Arms

• Experimental: Immediate Treatment
  Participants will take grazoprevir 100 mg + elbasvir 50 mg once daily during the 12-week treatment period and then will be monitored for safety during a 24-week follow-up period.
  Intervention: Drug: Grazoprevir + Elbasvir
• Placebo Comparator: Deferred Treatment
  Participants will take placebo tablets once daily during the 12-week treatment period and will then be monitored for safety during a 4-week follow-up period. Participants will then begin open-label treatment with grazoprevir 100 mg + elbasvir 50 mg for a 12-week treatment period and will then be monitored for safety during a 24-week follow-up period.
  Interventions:

  • Drug: Grazoprevir + Elbasvir
  • Drug: Placebo

Publications *

• Hezode C, Colombo M, Bourliere M, Spengler U, Ben-Ari Z, Strasser SI, Lee WM, Morgan L, Qiu J, Hwang P, Robertson M, Nguyen BY, Barr E, Wahl J, Haber B, Chase R, Talwani R, Marco VD; C-EDGE IBLD Study Investigators. Elbasvir/Grazoprevir for Patients With Hepatitis C Virus Infection and Inherited Blood Disorders: A Phase III Study. Hepatology. 2017 Sep;66(3):736-745. doi: 10.1002/hep.29139. Epub 2017 Jul 20.
• Asselah T, Reesink H, Gerstoft J, de Ledinghen V, Pockros PJ, Robertson M, Hwang P, Asante-Appiah E, Wahl J, Nguyen BY, Barr E, Talwani R, Serfaty L. Efficacy of elbasvir and grazoprevir in participants with hepatitis C virus genotype 4 infection: A pooled analysis. Liver Int. 2018 Sep;38(9):1583-1591. doi: 10.1111/liv.13727. Epub 2018 Mar 31.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 2, 2015): 159
• Original Estimated Enrollment (submitted: September 25, 2014): 200
• Actual Study Completion Date: June 14, 2016
• Actual Primary Completion Date: December 7, 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• has HCV GT1, GT4, or GT6 with sickle cell anemia, thalassemia, or hemophilia/von Willebrand disease
• has cirrhosis or is non-cirrhotic
• is human immunodeficiency virus (HIV) coinfected or not infected with HIV
• is a female of non childbearing potential, or is male or female and uses an acceptable method(s) of contraception

Exclusion Criteria:

• has evidence of decompensated liver disease
• is coinfected with hepatitis B
• has had a malignancy ≤5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer
• has hepatocellular carcinoma (HCC) or is under evaluation for HCC
• has clinically-relevant drug or alcohol abuse within 12 months of screening

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided
• Removed Location Countries: Australia, Canada, France, Germany, Greece, Israel, Italy, Thailand, United Kingdom, United States

Administrative Information

• NCT Number: NCT02252016
• Other Study ID Numbers: 5172-065; 2014-002356-27 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

• Current Responsible Party: Merck Sharp & Dohme LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Merck Sharp & Dohme LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme LLC

• PRS Account: Merck Sharp & Dohme LLC
• Verification Date: September 2018