Efficacy and Safety of Elbasvir (MK-8742) + Grazoprevir (MK-5172) in Treatment-Naïve/Treatment-Experienced (TN/TE) French Participants With Hepatitis C Virus (HCV) Genotype 4 (GT4) Infection (MK-5172-096)

May 28, 2020 updated by: Merck Sharp & Dohme LLC

A Multi-Site, Open-Label, Partially-Randomized Trial of the Efficacy and Safety of Fixed Dose Elbasvir/Grazoprevir (EBR/GZR) Based Regimens in French Subjects With Chronic Hepatitis C Virus (HCV) Genotype 4 Infection

The purpose of this study was to evaluate the efficacy of 8 and 12 weeks of treatment with a fixed dose combination (FDC) of elbasvir (EBR) 50 mg + grazoprevir (GZR) 100 mg (i.e., MK-5172A) as assessed by the percentage of participants with hepatitis C virus (HCV) genotype (GT) 4 infection that achieve sustained virologic response (HCV ribonucleic acid [RNA] < Lower Limit of Quantification [LLOQ]) 12 weeks after the end of study therapy (SVR12). This study also evaluated the safety and tolerability of EBR/GZR.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

117

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Amiens, France
        • CHU Amiens-Picardie - Hopital Sud ( Site 0217)
      • Besancon, France
        • CHU Jean Minjoz ( Site 0213)
      • Creteil, France
        • CHU Henri Mondor ( Site 0206)
      • Genoble, France
        • CHU de Grenoble - Hopital Michallon ( Site 0208)
      • Limoges, France
        • CHU Dupuytren ( Site 0209)
      • Montpellier, France
        • Hopital Saint Eloi ( Site 0207)
      • Nice, France
        • C.H.U. de Nice Hopital de l Archet 2 ( Site 0215)
      • Orleans, France
        • Centre Hospitalier Regional du Orleans ( Site 0212)
      • Paris, France
        • Hopital Beaujon ( Site 0201)
      • Paris, France
        • Hopital Cochin ( Site 0211)
      • Paris, France
        • Hopital Saint Antoine ( Site 0200)
      • Toulouse, France
        • CHU de Toulouse - Hopital Purpan ( Site 0216)
      • Vandoeuvre les Nancy, France
        • CHU de Nancy Hopital Brabois Adultes ( Site 0204)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Be a current resident of France
  • Have HCV RNA (≥ 10,000 IU/mL in peripheral blood) at the time of screening
  • Have documented chronic HCV GT4 (with no evidence of non-typeable or mixed genotype) infection
  • Have liver biopsy performed within 24 months of Day 1 of this study (if participant has cirrhosis, there is no time restriction on biopsy), or have FibroScan® performed within 12 months of Day 1 of this study with interpretable result in kilopascals (kPa) as follows: Fibrosis score of F0-F2, Fibrosis score of F3, or Cirrhosis (F4)
  • Have a prior treatment history of either HCV TN or HCV TE with interferon (IFN) +/- ribavirin (RBV) +/- Sofosbuvir (SOF) (on-treatment failure, relapser, or other/intolerant)
  • Females who are of reproductive potential must agree to avoid becoming pregnant while receiving study drug and for 14 days after the last dose of study drug by complying with one of the following: (1) practice abstinence from heterosexual activity OR (2) use (or have her partner use) acceptable contraception during heterosexual activity
  • If Human Immunodeficiency Virus (HIV) co-infected, then have HIV-1 infection documented prior to screening

Exclusion Criteria:

  • Had prior treatment (defined as 1 dose or more) with direct-acting antiviral (DAA) therapy
  • Has evidence of decompensated liver disease manifested by the presence of or history of ascites, esophageal or gastric variceal bleeding, hepatic encephalopathy, or other signs or symptoms of active advanced liver disease
  • Classified as Child-Pugh B or C or has a Child Pugh-Turcotte score (CPT) > 6
  • Has cirrhosis and liver imaging within 6 months of Day 1 showing evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC
  • Hepatitis B virus surface antigen (HBsAg) positive at screening. Participants who are HBsAg negative and hepatitis B core antibody (anti-HBc) positive at screening may be included
  • Under evaluation for active or suspected malignancy, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer Currently participating or has 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 such study during the course of this study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm 1: EBR/GZR for 8 Weeks
Treatment-naïve participants with stage 0-2 fibrosis (F0-F2) receive FDC of EBR/GZR (50 mg/100 mg) for 8 weeks, with 24 weeks of follow-up.
Drug: EBR/GZR (50 mg/100 mg) FDC
One FDC tablet taken once daily by mouth for 8 or 12 weeks depending upon randomization.
Other Names:
  • MK-5172A
Experimental: Arm 2: EBR/GZR for 12 Weeks
Treatment-naïve participants with F0-F2 stage fibrosis, treatment-naïve participants with F3-F4 stage fibrosis, and treatment-experienced participants with F0-F4 stage fibrosis receive FDC of EBR/GZR (50 mg/100 mg) for 12 weeks, with 24 weeks of follow-up.
Drug: EBR/GZR (50 mg/100 mg) FDC
One FDC tablet taken once daily by mouth for 8 or 12 weeks depending upon randomization.
Other Names:
  • MK-5172A

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After End of Treatment (SVR12)
Time Frame: 12 weeks after completing study treatment (Arm 1: Week 20 / Arm 2: Week 24)
The percentage of participants to achieve SVR12 was determined for each arm (SVR12 was defined as HCV ribonucleic acid [RNA] < lower limit of quantification [LLOQ] at 12 weeks after the end of all study therapy). Plasma HCV RNA was measured using the COBAS™ AmpliPrep/COBAS™ TaqMan HCV Test, v2.0®, which has a LLOQ of 15 IU/mL.
12 weeks after completing study treatment (Arm 1: Week 20 / Arm 2: Week 24)
Number of Participants With ≥ 1 Adverse Events (AEs)
Time Frame: Up to 14 weeks
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Up to 14 weeks
Number of Participants Who Discontinued From Study Treatment Due to an AE
Time Frame: Up to Study Week 12
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Up to Study Week 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After End of Treatment (SVR24)
Time Frame: 24 weeks after completing study treatment (Arm 1: Week 32 / Arm 2: Week 36)
The percentage of participants to achieve SVR24 was determined for each arm (SVR24 was defined as HCV RNA < LLOQ at 24 weeks after the end of all study therapy). Plasma HCV RNA was measured using the COBAS™ AmpliPrep/COBAS™ TaqMan HCV Test, v2.0®, which has a LLOQ of 15 IU/mL.
24 weeks after completing study treatment (Arm 1: Week 32 / Arm 2: Week 36)
Prevalence of Baseline NS3 Resistance-Associated Substitutions (RASs) to EBR or GZR
Time Frame: Day 1
Blood samples for viral resistance assays were collected at Baseline (Day 1) and analyzed for substitutions in the NS3 gene region. Results are pooled for all participants with baseline sequencing data available, and the number of participants with RASs is reported according HCV genotype. Resistance-associated substitutions are defined as amino acid substitutions that confer reduced susceptibility to a direct-acting antiviral (DAA) and may contribute to virologic failure. The prevalence of baseline substitutions in participants infected with HCV GT4 subtypes was assessed by evaluating amino acid substitutions in NS3.
Day 1
Prevalence of Baseline NS5A RASs to EBR or GZR
Time Frame: Day 1
Blood samples for viral resistance assays were collected at Baseline (Day 1) and analyzed for substitutions in the NS5A gene region. Results are pooled for all participants with baseline sequencing data available, and the number of participants with RASs is reported according HCV genotype. Resistance-associated substitutions are defined as amino acid substitutions that confer reduced susceptibility to a DAA and may contribute to virologic failure. The prevalence of baseline substitutions in participants infected with HCV GT4 subtypes was assessed by evaluating amino acid substitutions in NS5A.
Day 1

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck Sharp & Dohme LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 20, 2017

Primary Completion (Actual)

October 15, 2018

Study Completion (Actual)

October 15, 2018

Study Registration Dates

First Submitted

April 6, 2017

First Submitted That Met QC Criteria

April 6, 2017

First Posted (Actual)

April 12, 2017

Study Record Updates

Last Update Posted (Actual)

June 9, 2020

Last Update Submitted That Met QC Criteria

May 28, 2020

Last Verified

May 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 5172-096
  • 2016-001159-37 (EudraCT Number)
  • MK-5172-096 (Other Identifier: Merck Protocol Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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