Phase III, Multicenter Open-Label Study to Investigate the Efficacy of Elbasvir and Grazoprevir Fixed-Dose Combination for Eight Weeks in Treatment-Naïve, HCV GT1b-Infected Patients, with Non-Severe Fibrosis

Abstract

Background: Genotype 1b is the most common HCV genotype worldwide, accounting for the largest proportion of infections in Europe, Russia, Latin America and Asia. Reducing treatment duration can improve adherence, reduce drug exposure and cost. Accordingly, we evaluated the efficacy of eight weeks fixed dose combination of grazoprevir-elbasvir in treatment-naive patients, with non-severe fibrosis. Methods: HCV mono-infected and treatment naive patients with non-severe fibrosis (Fibroscan®<9·5kPa and Fibrotest®<0·59) were enrolled in a study which included 117 patients. Genotyping by sequencing identified five patients with non-1b genotype (two GT1a, one GT1h, one GT1e and one GT1l). Thus, we included in the final analysis 112 GT1b patients. The primary end point was the proportion of patients with HCVRNA below the lower limit of quantification 12 weeks after treatment (SVR12). Findings: Mean age was 54 ± 13 years, 31% were male, viral load was higher than 800.000 IU/ml in 70 out of 112 patients (63%). Using Fibroscan®, 100 had F0-1 fibrosis score. FIB-4 lower than 1·45 and APRI less than one was found in 74/112 (66%) and 107/112 (95%) patients respectively. Relapse occurred in three patients by week 12. These three patients had a viral load higher than 6 million IU/mL and NS5A Y93H RAS (resistance associated substitution). Then, modified intention-to-treat SVR12 for patients with genotype 1b was 109/112 (97%). By week 24; five relapses were observed and all had the Y93H RAS at relapse. SVR12 was achieved in 100% of patients with a baseline viral load below 6 million and decreased to 98% (98/100) by follow-up week 24. Interpretation: Naive patients with genotype 1b and non-severe fibrosis can achieve an SVR12 of 97% and an SVR24 of 95%. Then, these patients can be treated with grazoprevir-elbasvir for eight weeks. Funding Statement: The CHU of Clermont-Ferrand has received a grant of MSD to conduct the study. MSD has financed the cost of the treatment. The data were managed by the research assistants and the delegation a la recherche Clinique all in Clermont-Ferrand. Declaration of Interests: A Abergel : Clinical Investigator/Speaker: AbbVie, Gilead Sciences, Merck Sharp & Dohme, Intercept; T Asselah : Clinical Investigator/Speaker/Consultant: AbbVie, Bristol-Myers Squibb, Gilead Sciences, Janssen Pharmaceuticals, Merck Sharp & Dohme, and Roche; A Mallat : no conflict of interest; B Chanteranne : no conflict of interest; F Faure : no conflict of interest; D Larrey : Clinical Investigator/Speaker: AbbVie, Gilead Sciences, Merck Sharp & Dohme; J Gournay : personal fees from Gilead and Abbvie, grants and personal fees from Intercept; V Loustaud-Ratti : Clinical Investigator/Speaker: Abbvie, Gilead Sciences, Janssen Pharmaceuticals, Merck Sharp & Dohme; V Di Martino : personal fees from Abbvie and MSD; I Fouchard-Hubert : grants from Gilead and Abbvie outside the submitted work; S Pol has received consulting and lecturing fees from Bristol-Myers Squibb, Janssen, Gilead, Roche, MSD, Myr Pharma, Shionogi, Biotest and Abbvie, and grants from Bristol-Myers Squibb, Gilead, Roche and MSD; F Bailly : personal fees and non-financial support from MSD; personal fees and non-financial support from Gilead; personal fees and non-financial support from Abbvie; personal fees and non-financial support from Intercept; D Samuel : personnal fees from Intercept, Biotest, Abbvie, Gilead Sciences; A Tran : Clinical Investigator/Speaker/Consultant: AbbVie, Gilead Sciences, Merck Sharp & Dohme; M Dodel : no conflict of interest; N Andant : no conflict of interest; G Lamblin : no conflict of interest; L Muti : no conflict of interest; M Reymond : no conflict of interest; C Teilhet : no conflict of interest; B Pereira : no conflict of interest; B Buchard : no conflict of interest. Ethics Approval Statement: The study was approved by the ethical committee (CPP Sud-Est) on September 26, 2016 and met the ethical principles of the Declaration of Helsinki and Good Clinical Practice guidelines. All patients provides written informed consent.