Overview

This trial is active, not recruiting.

Condition hepatitis c
Treatments grazoprevir/elbasvir, sofosbuvir, ribavirin
Phase phase 2
Sponsor French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Start date January 2016
End date October 2016
Trial size 26 participants
Trial identifier NCT02647632, ANRS HC34 REVENGE

Summary

The primary objective of this study is to estimate, in HCV genotype 1 or 4-infected patients who failed a prior DAA bitherapy with Sofosbuvir, the efficacy of a treatment with Grazoprevir/Elbasvir, Sofosbuvir and Ribavirin in the two treatment groups and compare the rate of sustained virological response (SVR) 12 weeks after 16 or 24 weeks of this treatment. SVR12 is defined as HCV RNA < LLOQ (either TD[u] or TND).

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Drug : Grazoprevir/Elbasvir + Sofosbuvir + Ribavirin during 16 weeks
grazoprevir/elbasvir Grazoprevir/Elbasvir is also known as MK-5172A or Zepatier
sofosbuvir Sofosbuvir is also known as Sovaldi
ribavirin Ribavirin is also known as Rebetol
(Experimental)
Drug : Grazoprevir/Elbasvir + Sofosbuvir + Ribavirin during 24 weeks
grazoprevir/elbasvir Grazoprevir/Elbasvir is also known as MK-5172A or Zepatier
sofosbuvir Sofosbuvir is also known as Sovaldi
ribavirin Ribavirin is also known as Rebetol

Primary Outcomes

Measure
rate of the Sustained Virological Response 12 weeks after the end of the therapy (SVR12), i.e. at W28 or W36 for treatment duration of 16 weeks and 24 weeks respectively.
time frame: Week 28 (W28) or Week 36 (W36)

Secondary Outcomes

Measure
SVR rate 4 weeks after the end of treatment (i.e. at week 20 or week 28 for treatment duration of 16 weeks and 24 weeks respectively) and 24 weeks after the end of treatment (i.e. at week 40 or week 48).
time frame: Week 20 (W20) or Week 28 (W28), and W40 or W48
HCV viral load assessment
time frame: from Day 0 (D0) to Week 40 (W40) or Week 48 (W48)
Assessment of HCV subtypic distribution at baseline
time frame: Pre-inclusion
Numbers and proportions of patients presenting variants of resistance (RAV) at baseline
time frame: Pre-inclusion
Assessment of liver fibrosis by Hepatic impulse elastometry (Fibroscan®)
time frame: Pre-inclusion, Week 40 or Week 48
For cirrhotic patients, description of the risk of cirrhosis evolution (decompensation, hepatocarcinoma)
time frame: Pre-inclusion, Day 0 (D0), Week 16 (W16), W20, W24, W28, W36, W40 or W48
For cirrhotic patients, description of the risk of cirrhosis evolution (decompensation, hepatocarcinoma)
time frame: Pre-inclusion, Day 0 (D0), Week 16 (W16), W20, W24, W28, W36, W40 or W48
Clinical and biological adverse events occurring during the treatment and until 24 weeks after the end of the treatment
time frame: from Day 0(D0) to Week 40 (W40) or W48
Numbers and proportions of patients who interrupted the treatments of the study
time frame: from Day 0 (D0) to Week 40 (W40) or W48
Patient's reported outcomes evaluation with questionnaires
time frame: Day 0 (D0), Week 4 (W4), W16, W28, W40 or D0, W4, W16, W24, W36, W48 (24 weeks treatment-arm))
Patient's reported outcomes evaluation with questionnaires
time frame: Day 0 (D0), Week 4 (W4), W16, W28, W40 or D0, W4, W16, W24, W36, W48 (24 weeks treatment-arm))

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Adult ≥18 years - Infection with HCV genotype 1 or 4, confirmed by detectable HCV RNA at pre-inclusion - Failure to a prior therapy with Sofosbuvir +/- Ribavirin associated with Simeprevir or Daclatasvir or Ledipasvir, with documented presence of NS5A or NS3/4A RAVs (Resistance Associated Variants) at the time of failure (presence of RAVs on at least one sample since the time of failure). The proportion of patients previously treated with Simeprevir will be limited to a third of all patients included. - Fibrosis at any stage - Men and women of child-bearing age and their heterosexual partners must use adequate contraceptions from 15 days before their inclusion in the study up to 7 months after the end of treatment for men and up to 4 months after the end of treatment for women - Written informed consent signed by the patient and the investigator (on the day of the pre-inclusion at the latest and before any examination required by the study) (article L1122-1-1 Public Health Code) - Patients with Health insurance (Sécurité Sociale or Couverture Médicale Universelle) Exclusion Criteria: - Child B or C cirrhosis (or Child A patients with history of Child B) - Patients with documented presence of RAVs conferring resistance to sofosbuvir - Positive HBs Antigen - Confirmed HIV-1 or HIV-2 infection - Pregnant or breast-feeding women or men whose female partners are pregnant - Transplant recipients - Any evolutive ongoing malignant disease, including hepatocellular carcinoma, which will be specifically screened for before inclusion - History of severe rhythm disorders or cardiac disease (coronary artery disease, heart failure, arteriopathy,…): the opinion of a cardiologist is compulsory (< 6 months) - Consumption of alcohol which, in the investigator's opinion, will be an obstacle to the patient's participation and to his/her remaining in the study - Drug addiction which, in the investigator's opinion, will be an obstacle to the patient's participation and to his/her remaining in the study. Patients included in a programme of substitution with methadone or buprenorphine could be included. The opinion of an addictology consultant is recommended for patients presenting with current drug use or drug use in the past year - Patients taking part in another clinical trial within 30 days prior to inclusion - Patient under guardianship, trusteeship or judicial protection Non-inclusion biological criteria - Hemoglobin < 11 g/dL - Platelets < 50 000/mm3 - INR > 1.5 unless subject has known hemophilia or is stable on an anticoagulant regimen affecting INR - ALT or AST > 10xULN - Direct bilirubin > 1.5xULN - Creatinine clearance < 50 mL/mn (MDRD formula) - Albumin < 30 g/L - HbA1c > 10% (only in diabetic patients) Criteria related to study drugs - Contra-indication to treatment with Grazoprevir/Elbasvir, Sofosbuvir or Ribavirin including a history of hypersensitivity to one of their excipients - Patients with a non-compliance history, who will be at risk of not complying with the study follow-up timetable - Treatment with contra-indicated associated drugs

Additional Information

Official title Study to Assess Efficacy and Safety of Grazoprevir/Elbasvir Associated With Sofosbuvir and Ribavirin in HCV Genotype 1 or 4-infected Patients Who Failed Direct Acting Antivirals (DAA) Bitherapy With Sofosbuvir
Principal investigator Victor DE LEDINGHEN
Trial information was received from ClinicalTrials.gov and was last updated in July 2016.
Information provided to ClinicalTrials.gov by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS).