Clinical trial NCT03111108: 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)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hepatitis C Virus (HCV) Infection
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2017-04-12
Enrollment: 117
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After End of Treatment (SVR12)
timeFrame: 12 weeks after completing study treatment (Arm 1: Week 20 / Arm 2: Week 24)
measure: Number of Participants With ≥ 1 Adverse Events (AEs)
timeFrame: Up to 14 weeks
measure: Number of Participants Who Discontinued From Study Treatment Due to an AE
timeFrame: Up to Study Week 12
Secondary outcomes:
measure: Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After End of Treatment (SVR24)
timeFrame: 24 weeks after completing study treatment (Arm 1: Week 32 / Arm 2: Week 36)
measure: Prevalence of Baseline NS3 Resistance-Associated Substitutions (RASs) to EBR or GZR
timeFrame: Day 1
measure: Prevalence of Baseline NS5A RASs to EBR or GZR
timeFrame: Day 1
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU Amiens-Picardie - Hopital Sud ( Site 0217)
city: Besancon
country: France
facility: CHU Jean Minjoz ( Site 0213)
city: Creteil
country: France
facility: CHU Henri Mondor ( Site 0206)
city: Genoble
country: France
facility: CHU de Grenoble - Hopital Michallon ( Site 0208)
city: Limoges
country: France
facility: CHU Dupuytren ( Site 0209)
city: Montpellier
country: France
facility: Hopital Saint Eloi ( Site 0207)
city: Nice
country: France
facility: C.H.U. de Nice Hopital de l Archet 2 ( Site 0215)
city: Orleans
country: France
facility: Centre Hospitalier Regional du Orleans ( Site 0212)
city: Paris
country: France
facility: Hopital Beaujon ( Site 0201)
city: Paris
country: France
facility: Hopital Cochin ( Site 0211)
city: Paris
country: France
facility: Hopital Saint Antoine ( Site 0200)
city: Toulouse
country: France
facility: CHU de Toulouse - Hopital Purpan ( Site 0216)
city: Vandoeuvre les Nancy
country: France
facility: CHU de Nancy Hopital Brabois Adultes ( Site 0204)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.