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

NCT ID: NCT02647632

Last Updated: 2017-06-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-31
• Study Completion Date: 2017-04-30

Brief 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).

Conditions

Hepatitis C

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

16 weeks of treatment

Drug : Grazoprevir/Elbasvir + Sofosbuvir + Ribavirin during 16 weeks

Group Type: EXPERIMENTAL

Grazoprevir/Elbasvir

Intervention Type: DRUG

Sofosbuvir

Intervention Type: DRUG

Ribavirin

Intervention Type: DRUG

24 weeks of treatment

Drug : Grazoprevir/Elbasvir + Sofosbuvir + Ribavirin during 24 weeks

Group Type: EXPERIMENTAL

Grazoprevir/Elbasvir

Intervention Type: DRUG

Sofosbuvir

Intervention Type: DRUG

Ribavirin

Intervention Type: DRUG

Interventions

Grazoprevir/Elbasvir

Intervention Type: DRUG

Sofosbuvir

Intervention Type: DRUG

Ribavirin

Intervention Type: DRUG

Other Intervention Names

Grazoprevir/Elbasvir is also known as MK-5172A or Zepatier; Sofosbuvir is also known as Sovaldi; Ribavirin is also known as Rebetol

Eligibility Criteria

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
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ANRS, Emerging Infectious Diseases

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Victor DE LEDINGHEN

Role: PRINCIPAL_INVESTIGATOR

Hôpital de Haut-Lévêque, CHU de Bordeaux

Eric BELLISSANT

Role: STUDY_CHAIR

Centre de Méthodologie et de Gestion, CHU de Rennes

References

de Ledinghen V, Laforest C, Hezode C, Pol S, Renault A, Alric L, Larrey D, Metivier S, Tran A, Jezequel C, Samuel D, Zoulim F, Tual C, Pailhe A, Gibowski S, Bourliere M, Bellissant E, Pawlotsky JM. Retreatment With Sofosbuvir Plus Grazoprevir/Elbasvir Plus Ribavirin of Patients With Hepatitis C Virus Genotype 1 or 4 Who Previously Failed an NS5A- or NS3-Containing Regimen: The ANRS HC34 REVENGE Study. Clin Infect Dis. 2018 Mar 19;66(7):1013-1018. doi: 10.1093/cid/cix916.

Reference Type: DERIVED

PMID: 29077864 (View on PubMed)

Other Identifiers

ANRS HC34 REVENGE

Identifier Type: -

Identifier Source: org_study_id