Study to Investigate the Efficacy of Elbasvir/Grazoprevir Fixed-Dose Combination for 8 Weeks in Treatment-Naïve, HCV GT1b-Infected Patients, With Non-severe Fibrosis

NCT02973503 | Completed Phase 3 Results

• 2 other identifiers: CHU-02852016-001363-37
• Study Type: interventional
• Target: 117
• Locations: 1 country
• Sites: 1

Brief Summary

A Phase 3, Global, Multicenter, Open-Label Study to Investigate the Efficacy of Elbasvir/Grazoprevir Fixed-Dose Combination for 8 Weeks in Treatment-Naïve, HCV GT1b-Infected Patients, with non-severe fibrosis The primary objectives of this study are as follows:

• To evaluate the efficacy of Elbasvir/Grazoprevir Fixed-Dose Combination for 8 Weeks in Treatment-Naïve, HCV GT1b-Infected Patients, with non- severe fibrosis as measured by the proportion of subjects with sustained viral response 12 weeks after cessation of treatment (SVR 12).
• To evaluate the safety and tolerability of EBV/GZR treatment The secondary objectives of this study are as follows:
• To determine the proportion of subjects who attain SVR at 4 and 24 weeks after cessation of treatment (SVR4 and SVR24)
• To evaluate the proportion of subjects with virologic failure
• To evaluate the kinetics of circulating HCV RNA during treatment and after cessation of treatment.
• To evaluate the emergence of viral resistance to EBV/GZR during treatment and after cessation of treatment

Conditions

Chronic HCV Infection

Keywords

Hepatitis C; Genotype 1B; Non Severe Fibrosis; Treatment Naïve; 8 Weeks of Treatment; Elbasvir/Grazoprevir Combination

Outcome Measures

Primary Outcomes (1)

• Evaluation of the Efficacy of of Elbasvir/Grazoprevir Fixed-Dose Combination for 8 Weeks in Treatment-Naïve as Measured by the Proportion of Subjects With Sustained Viral Response 12 Weeks After Cessation of Treatment (SVR 12).

  Blood samples for HCV RNA determination were collected 12 weeks after cessation of treatment and analysed by local laboratories tests

  at 12 weeks post-treatment

Secondary Outcomes (7)

• Evaluation of the Safety and Tolerability of EBV/GZR Treatment by Number of Patients With Treatment-related Asthenia Reported

  Between the first day of treatment to 24 weeks after the end of treatment, an average of 32 weeks

• Evaluation of the Safety and Tolerability of EBV/GZR Treatment by Number of Patients With Treatment-related Headache Reported

  between the first day of treatment to 24 weeks after the end of treatment, an average of 32 weeks

• Evaluation of the Safety and Tolerability of EBV/GZR Treatment by Number of Patients With Treatment-related Digestive Disorders Reported

  Between the first day of treatment to 24 weeks after the end of treatment, an average of 32 weeks

• Percentage of Subjects Who Attain SVR at 4 Weeks After Cessation of Treatment (SVR4)

  at 4 weeks after cessation of treatment

• Percentage of Subjects Who Attain SVR 24 Weeks After Cessation of Treatment (SVR 24)

  at 24 weeks after cessation of treatment

Study Arms (1)

Elbasvir/Grazoprevir

EXPERIMENTAL

evaluate the efficacy of Elbasvir/Grazoprevir Fixed-Dose Combination for 8 Weeks in Treatment-Naïve, HCV GT1b-Infected Patients, with non- severe fibrosis as measured by the proportion of subjects with sustained viral response 12 weeks after cessation of treatment (SVR 12).

Drug: Elbasvir/Grazoprevir Fixed Dose Combination

Interventions

Elbasvir/Grazoprevir Fixed Dose Combination DRUG

Evaluate the efficacy of Elbasvir/Grazoprevir Fixed-Dose Combination for 8 Weeks in Treatment-Naïve, HCV GT1b-Infected Patients, with non- severe fibrosis as measured by the proportion of subjects with sustained viral response 12 weeks after cessation of treatment (SVR 12).

Elbasvir/Grazoprevir

Eligibility Criteria

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

You may qualify if:

• Willing and able to provide written informed consent
• Male or female, age ≥ 18 years
• Body Mass Index (BMI) ≥ 18 kg/m2
• HCV RNA ≥ 100 000 IU/mL at Screening
• Chronic HCV infection (≥ 6 months) documented by prior medical history or liver biopsy, only genotype 1b virus. (Positive for anti HCV antibody, HCV RNA, or an HCV genotype)
• Treatment-naïve with no prior exposure to any IFN, RBV, or approved or experimental HCV-specific DAA
• Non severe fibrosis (F\<2) according to combination of this two tests :
• Fibroscan lower than 9.5kPa and Fibrotest lower than 0.59
• Females of childbearing potential (as defined in protocol Appendix 4) must have a negative serum pregnancy test at screening and a negative urine pregnancy test on Day 1 prior to enrollment
• Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use 2 effective method(s) of contraception from at least two weeks prior to Day 1 through 14 days after the last dose of study drugs.
• If acceptable by local regulatory agencies, methods of birth control allowed in the study are: intrauterine device (IUD), diaphragm with spermicide, hormonal contraceptives (e.g., birth control pills, transdermal patch, or injectables), contraceptive sponge, female condom, male condom with spermicide or vasectomy.
• Note: Periodic abstinence (e.g., abstinence only on certain calendar days, abstinence only during ovulation period, use of symptothermal methods, use of post-ovulation methods and withdrawal) are not acceptable methods of contraception.
• A female subject who is not of reproductive potential is eligible without requiring the use of contraception. A female subjects who is not of reproductive potentials is defined as one who has either 1) reached natural menopause (defined as 12 months with no menses without an alternative medical cause), 2) 6 weeks post surgical bilateral oophorectomy with or without hysterectomy, or 3) bilateral tubal ligation.
• A male subject who is not of reproductive potential is eligible without requiring the use of contraception. A male subject who is not of reproductive potential is defined as: one who has undergone a successful vasectomy. A successful vasectomy is defined as: (1) microscopic documentation of azoospermia, or (2) a vasectomy more than 2 years ago with no resultant pregnancy despite sexual activity post vasectomy.
• Lactating females must agree to discontinue nursing before starting study drug

You may not qualify if:

• Is under the age of legal consent, is mentally or legally incapacitated, has significant emotional problems at the time of pre-study screening visit or expected during the conduct of the study or has a history of a clinically significant psychiatric disorder which, in the opinion of the investigator, would interfere with the study procedures.
• Current or prior history of any of the following:
• Clinically significant illness (other than HCV) or any other major medical disorder that may interfere with subject treatment, assessment or compliance with the protocol; subjects currently under evaluation for a potentially clinically significant illness (other than HCV) are also excluded
• Gastrointestinal disorder or post-operative condition that could interfere with the absorption of the study drug
• Difficulty with blood collection and/or poor venous access for the purposes of phlebotomy
• History of decompensation (e.g., clinical ascites, encephalopathy, and/or variceal hemorrhage)
• Solid organ transplantation (including hematopoietic stem cell transplants) other than kidney, cornea and hair.
• Significant cardiac disease
• Unstable psychiatric condition including hospitalization, suicidal attempt, and/or a period of disability as a result of their psychiatric illness within 2 years prior to Screening
• Malignancy within the 5 years prior to Screening, with the exception of specific cancers that have been cured by surgical resection (e.g., basal cell skin cancer, etc.). Subjects under evaluation for possible malignancy are not eligible
• Significant drug allergy (e.g., hepatotoxicity)
• Subject has the following laboratory parameters at Screening:
• ALT \> 10 x the upper limit of normal (ULN)
• AST \> 10 x ULN
• Direct bilirubin \> 1.5 x ULN

Sponsors & Collaborators

• University Hospital, Clermont-Ferrand: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

CHU Clermont-Ferrand

Clermont-Ferrand, 63003, France

Location

MeSH Terms

Conditions

Hepatitis C

Interventions

elbasvir; grazoprevir

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

Limitations and Caveats

5 patients were non genotype 1b so they were excluded from the analysis. Patients must have genotype 1b and non severe fibrosis to be treated by 8 weeks elbasvir grazoprevir

Results Point of Contact

• Title: Armand Abergel
• Organization: CHU Clermont-Ferrand

aabergel@chu-clermontferrand.fr

+33473750523

Study Officials

• Armand ABERGEL

  University Hospital, Clermont-Ferrand

  PRINCIPAL INVESTIGATOR

• Isabelle FOUCHART-HUBERT

  University Hospital, Angers

  PRINCIPAL INVESTIGATOR

• Vincent DI MARTINO

  Centre Hospitalier Universitaire de Besancon

  PRINCIPAL INVESTIGATOR

• Véronique LOUSTAUD RATTI

  CHU LIMOGES

  PRINCIPAL INVESTIGATOR

• Jérôme GOURNAY

  Nantes University Hospital

  PRINCIPAL INVESTIGATOR

• Tarik ASSELAH

  Hôpital Beaujon

  PRINCIPAL INVESTIGATOR

• Didier SAMUEL

  Hôpital Paul Brousse

  PRINCIPAL INVESTIGATOR

• Dominique LARREY

  University Hospital, Montpellier

  PRINCIPAL INVESTIGATOR

• Sophie METIVIER

  CHU Toulouse Hopital Purpan

  PRINCIPAL INVESTIGATOR

• Christophe HEZODE

  CHU Henri Mondor

  PRINCIPAL INVESTIGATOR

• Albert TRAN

  CHU Nice hopital Archet II

  PRINCIPAL INVESTIGATOR

• François BAILLY

  Hospice civils de Lyon, hopital de la croix Rousse

  PRINCIPAL INVESTIGATOR

• Stanislas POL

  AP-HP Hopital Cochin

  PRINCIPAL INVESTIGATOR

• Valérie CANVA

  CHU de Lille

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2016
• First Posted: November 25, 2016
• Study Start: January 11, 2017
• Primary Completion: November 10, 2018
• Study Completion: April 1, 2019
• Last Updated: October 1, 2020
• Results First Posted: September 7, 2020

Record last verified: 2020-09

Locations

FR (1)