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Trial record 21 of 82 for:    GRAZOPREVIR ANHYDROUS AND ELBASVIR

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

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ClinicalTrials.gov Identifier: NCT02647632
Recruitment Status : Completed
First Posted : January 6, 2016
Last Update Posted : June 29, 2017
Sponsor:
Information provided by (Responsible Party):
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)

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).

Condition or disease Intervention/treatment Phase
Hepatitis C Drug: Grazoprevir/Elbasvir Drug: Sofosbuvir Drug: Ribavirin Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 26 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : January 2016
Actual Primary Completion Date : January 2017
Actual Study Completion Date : April 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hepatitis

Arm Intervention/treatment
Experimental: 16 weeks of treatment
Drug : Grazoprevir/Elbasvir + Sofosbuvir + Ribavirin during 16 weeks
Drug: Grazoprevir/Elbasvir
Other Name: Grazoprevir/Elbasvir is also known as MK-5172A or Zepatier

Drug: Sofosbuvir
Other Name: Sofosbuvir is also known as Sovaldi

Drug: Ribavirin
Other Name: Ribavirin is also known as Rebetol

Experimental: 24 weeks of treatment
Drug : Grazoprevir/Elbasvir + Sofosbuvir + Ribavirin during 24 weeks
Drug: Grazoprevir/Elbasvir
Other Name: Grazoprevir/Elbasvir is also known as MK-5172A or Zepatier

Drug: Sofosbuvir
Other Name: Sofosbuvir is also known as Sovaldi

Drug: Ribavirin
Other Name: Ribavirin is also known as Rebetol




Primary Outcome Measures :
  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. [ Time Frame: Week 28 (W28) or Week 36 (W36) ]
    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.


Secondary Outcome Measures :
  1. 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 ]
  2. HCV viral load assessment [ Time Frame: from Day 0 (D0) to Week 40 (W40) or Week 48 (W48) ]
  3. Assessment of HCV subtypic distribution at baseline [ Time Frame: Pre-inclusion ]
  4. Numbers and proportions of patients presenting variants of resistance (RAV) at baseline [ Time Frame: Pre-inclusion ]
    The numbers and proportions of patients presenting variants of resistance (RAV) and their characteristics will be studied

  5. Assessment of liver fibrosis by Hepatic impulse elastometry (Fibroscan®), or biological parameters (FibroMeter® or Fibrotest®) [ Time Frame: Pre-inclusion, Week 40 or Week 48 ]
  6. 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 ]
    Cirrhosis evaluation (Child-Pugh)

  7. 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 ]
    Cirrhosis evaluation (MELD score)

  8. 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 ]
  9. Numbers and proportions of patients who interrupted the treatments of the study [ Time Frame: from Day 0 (D0) to Week 40 (W40) or W48 ]
  10. 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)) ]
    Evaluation of patient's quality of life

  11. 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)) ]
    Evaluation of perceived symptoms (ANRS questionnaire)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02647632


Sponsors and Collaborators
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Investigators
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Principal Investigator: Victor DE LEDINGHEN Hôpital de Haut-Lévêque, CHU de Bordeaux
Study Chair: Eric BELLISSANT Centre de Méthodologie et de Gestion, CHU de Rennes

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
ClinicalTrials.gov Identifier: NCT02647632     History of Changes
Other Study ID Numbers: ANRS HC34 REVENGE
First Posted: January 6, 2016    Key Record Dates
Last Update Posted: June 29, 2017
Last Verified: June 2017
Keywords provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):
HCV genotype 1 or 4
failure to DAA
Additional relevant MeSH terms:
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MK-5172
Hepatitis C
Hepatitis
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Flaviviridae Infections
RNA Virus Infections
Ribavirin
Antiviral Agents
Sofosbuvir
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Anti-Infective Agents