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)

NCT03111108 | Completed Phase 4 Results

• 3 other identifiers: 5172-0962016-001159-37MK-5172-096
• Study Type: interventional
• Target: 117
• Locations: 1 country
• Sites: 13

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.

Conditions

Hepatitis C Virus (HCV) Infection

Outcome Measures

Primary Outcomes (3)

• Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After End of Treatment (SVR12)

  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)

  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

  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 Outcomes (3)

• Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After End of Treatment (SVR24)

  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

  Day 1

• Prevalence of Baseline NS5A RASs to EBR or GZR

  Day 1

Study Arms (2)

Arm 1: EBR/GZR for 8 Weeks

EXPERIMENTAL

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

Arm 2: EBR/GZR for 12 Weeks

EXPERIMENTAL

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

Interventions

EBR/GZR (50 mg/100 mg) FDC DRUG

One FDC tablet taken once daily by mouth for 8 or 12 weeks depending upon randomization.

Also known as: MK-5172A

Arm 1: EBR/GZR for 8 Weeks; Arm 2: EBR/GZR for 12 Weeks

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (13)

CHU Amiens-Picardie - Hopital Sud ( Site 0217)

Amiens, France

Location

CHU Jean Minjoz ( Site 0213)

Besançon, France

Location

CHU Henri Mondor ( Site 0206)

Créteil, France

Location

CHU de Grenoble - Hopital Michallon ( Site 0208)

Genoble, France

Location

CHU Dupuytren ( Site 0209)

Limoges, France

Location

Hopital Saint Eloi ( Site 0207)

Montpellier, France

Location

C.H.U. de Nice Hopital de l Archet 2 ( Site 0215)

Nice, France

Location

Centre Hospitalier Regional du Orleans ( Site 0212)

Orléans, France

Location

Hopital Beaujon ( Site 0201)

Paris, France

Location

Hopital Cochin ( Site 0211)

Paris, France

Location

Hopital Saint Antoine ( Site 0200)

Paris, France

Location

CHU de Toulouse - Hopital Purpan ( Site 0216)

Toulouse, France

Location

CHU de Nancy Hopital Brabois Adultes ( Site 0204)

Vandœuvre-lès-Nancy, France

Location

Related Publications (1)

• Asselah T, Pol S, Hezode C, Loustaud-Ratti V, Leroy V, Ahmed SNS, Ozenne V, Bronowicki JP, Larrey D, Tran A, Alric L, Nguyen-Khac E, Robertson MN, Hanna GJ, Brown D, Asante-Appiah E, Su FH, Hwang P, Hall JD, Guidoum A, Hagen K, Haber BA, Talwani R, Serfaty L. Efficacy and safety of elbasvir/grazoprevir for 8 or 12 weeks for hepatitis C virus genotype 4 infection: A randomized study. Liver Int. 2020 May;40(5):1042-1051. doi: 10.1111/liv.14313. Epub 2020 Mar 22.

  PMID: 31765046 RESULT

MeSH Terms

Conditions

Hepatitis C; Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 6, 2017
• First Posted: April 12, 2017
• Study Start: June 20, 2017
• Primary Completion: October 15, 2018
• Study Completion: October 15, 2018
• Last Updated: June 9, 2020
• Results First Posted: November 12, 2019

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will share

Locations

FR (13)