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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)

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ClinicalTrials.gov Identifier: NCT03111108
Recruitment Status : Completed
First Posted : April 12, 2017
Results First Posted : November 11, 2019
Last Update Posted : November 11, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Hepatitis C Virus (HCV) Infection Drug: EBR/GZR (50 mg/100 mg) FDC Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 117 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : June 20, 2017
Actual Primary Completion Date : October 15, 2018
Actual Study Completion Date : October 15, 2018

Resource links provided by the National Library of Medicine


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 Name: 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 Name: MK-5172A




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03111108


Locations
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France
CHU Amiens-Picardie - Hopital Sud ( Site 0217)
Amiens, France
CHU Jean Minjoz ( Site 0213)
Besancon, France
CHU Henri Mondor ( Site 0206)
Creteil, France
CHU de Grenoble - Hopital Michallon ( Site 0208)
Genoble, France
CHU Dupuytren ( Site 0209)
Limoges, France
Hopital Saint Eloi ( Site 0207)
Montpellier, France
C.H.U. de Nice Hopital de l Archet 2 ( Site 0215)
Nice, France
Centre Hospitalier Regional du Orleans ( Site 0212)
Orleans, France
Hopital Beaujon ( Site 0201)
Paris, France
Hopital Cochin ( Site 0211)
Paris, France
Hopital Saint Antoine ( Site 0200)
Paris, France
CHU de Toulouse - Hopital Purpan ( Site 0216)
Toulouse, France
CHU de Nancy Hopital Brabois Adultes ( Site 0204)
Vandoeuvre les Nancy, France
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.
  Study Documents (Full-Text)

Documents provided by Merck Sharp & Dohme Corp.:

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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT03111108     History of Changes
Other Study ID Numbers: 5172-096
2016-001159-37 ( EudraCT Number )
MK-5172-096 ( Other Identifier: Merck Protocol Number )
First Posted: April 12, 2017    Key Record Dates
Results First Posted: November 11, 2019
Last Update Posted: November 11, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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MK-5172
Infection
Communicable Diseases
Hepatitis A
Hepatitis C
Hepatitis
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Antiviral Agents
Anti-Infective Agents