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

NCT02647632 | Completed Phase 2

• 1 other identifier: ANRS HC34 REVENGE
• Study Type: interventional
• Target: 26
• Locations: 0 countries
• Sites: N/A

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

Keywords

HCV genotype 1 or 4; failure to DAA

Outcome Measures

Primary Outcomes (1)

• 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.

  The primary endpoint is the rate of the Sustained Virological Response defined as HCV RNA \< LLOQ (either TD\[u\] or TND) 12 weeks after the end of the therapy associating Grazoprevir/Elbasvir, Sofosbuvir and Ribavirin (SVR12), i.e. at W28 or W36 for treatment duration of 16 weeks and 24 weeks respectively.

  Week 28 (W28) or Week 36 (W36)

Secondary Outcomes (11)

• 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).

  Week 20 (W20) or Week 28 (W28), and W40 or W48

• HCV viral load assessment

  from Day 0 (D0) to Week 40 (W40) or Week 48 (W48)

• Assessment of HCV subtypic distribution at baseline

  Pre-inclusion

• Numbers and proportions of patients presenting variants of resistance (RAV) at baseline

  Pre-inclusion

• Assessment of liver fibrosis by Hepatic impulse elastometry (Fibroscan®), or biological parameters (FibroMeter® or Fibrotest®)

  Pre-inclusion, Week 40 or Week 48

Study Arms (2)

16 weeks of treatment

EXPERIMENTAL

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

Drug: Grazoprevir/Elbasvir; Drug: Sofosbuvir; Drug: Ribavirin

24 weeks of treatment

EXPERIMENTAL

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

Drug: Grazoprevir/Elbasvir; Drug: Sofosbuvir; Drug: Ribavirin

Interventions

Grazoprevir/Elbasvir DRUG

Also known as: Grazoprevir/Elbasvir is also known as MK-5172A or Zepatier

16 weeks of treatment; 24 weeks of treatment

Sofosbuvir DRUG

Also known as: Sofosbuvir is also known as Sovaldi

16 weeks of treatment; 24 weeks of treatment

Ribavirin DRUG

Also known as: Ribavirin is also known as Rebetol

16 weeks of treatment; 24 weeks of treatment

Eligibility Criteria

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

You may qualify if:

• Adult ≥18 years
• 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
• Patients with Health insurance (Sécurité Sociale or Couverture Médicale Universelle)

You may not qualify if:

• 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
• 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
• Patient under guardianship, trusteeship or judicial protection
• 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)

Sponsors & Collaborators

• ANRS, Emerging Infectious Diseases: lead

Related Publications (1)

• 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.

  PMID: 29077864 DERIVED

MeSH Terms

Conditions

Hepatitis C

Interventions

elbasvir-grazoprevir drug combination; grazoprevir; Sofosbuvir; Ribavirin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Uridine Monophosphate; Uracil Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides; Ribonucleosides; Nucleosides

Study Officials

• Victor DE LEDINGHEN

  Hôpital de Haut-Lévêque, CHU de Bordeaux

  PRINCIPAL INVESTIGATOR

• Eric BELLISSANT

  Centre de Méthodologie et de Gestion, CHU de Rennes

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2015
• First Posted: January 6, 2016
• Study Start: January 1, 2016
• Primary Completion: January 1, 2017
• Study Completion: April 1, 2017
• Last Updated: June 29, 2017

Record last verified: 2017-06