Phase IIb Study to Evaluate the Efficacy and Safety of GFT505 Versus Placebo in Patients With Non-Alcoholic Steatohepatitis (NASH)

NCT ID: NCT01694849

Last Updated: 2022-11-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 275 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-09-30
• Study Completion Date: 2015-12-31

Brief Summary

Abdominal obesity and type-2 Diabetes are associated with chronic liver disorders resulting from the accumulation of fat in the liver (steatosis), which may progress towards hepatitis and possibly lead to cirrhosis and liver cancer. NAFLD (Non Alcoholic Fatty Liver Disease) is considered as the most common form of chronic liver disease in adults in the United States, Australia, Asia and Europe. In the USA, the estimated prevalence of NAFLD is 20-30% of the adult population.

Non-alcoholic Steatohepatitis (NASH) is a progressing form of NAFLD, which corresponds to hepatic steatosis associated with inflammation and liver cell injury upon microscopic examination of a liver biopsy. This condition may lead to advanced fibrosis and cirrhosis and deserves serious medical management. Up to now, there is no effective drug which has clearly demonstrated therapeutic efficacy which may help lifestyle and dietary recommendations in the resolution of NASH.

In this context, GENFIT is developing a new liver targeted drug candidate, GFT505, for the treatment of NASH and the reduction of multiple cardiometabolic risk factors associated with the metabolic syndrome and type 2 Diabetes.

This phase IIb study will evaluate the efficacy and safety of GFT505 80mg and 120mg once daily for 52 weeks on the reversal of NASH without worsening of fibrosis, based on liver biopsy assessments.

Detailed Description

The study duration per patient will be 80 weeks. A screening period (from 4 to 16 weeks) will precede a 52-week double-blind treatment period and a 3 months follow-up period.

The study will be conducted in 270 patients (90 patients in the placebo arm, 90 patients in the GFT505 80mg arm, and 90 patients in the GFT505 120mg arm).

Enrollment will be performed in two phases: during the first phase, the patients will receive either GFT505 at a dose of 80 mg either the placebo. An independent expert committee will review the safety data when 45 patients receiving the dose at 80 mg will have been treated for 6 months. The committee approval will be necessary to start the second phase, while the patients will receive either GFT505 at a dose of 80 mg, or GFT505 at a dose of 120 mg or the placebo.

Conditions

Non-Alcoholic Steatohepatitis (NASH)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

GFT505 80mg

Hard gelatin capsules dosed at 40mg, oral administration, 3 capsules per day before breakfast with a glass of water.

Group Type: EXPERIMENTAL

GFT505 80mg

Intervention Type: DRUG

GFT505 120mg

Hard gelatin capsules dosed at 40mg, oral administration, 3 capsules per day before breakfast with a glass of water.

Group Type: EXPERIMENTAL

GFT505 120mg

Intervention Type: DRUG

Placebo

hard gelatin capsules, oral administration, 3 capsules per day before breakfast with a glass of water.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

GFT505 80mg

Intervention Type: DRUG

GFT505 120mg

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Males or females (females must be either of non-child bearing potential or using an efficient double contraception). For male participants, contraceptive measures must be taken during the study, either by the male participant or his female partner.
• Body Mass Index ≤ 45 kg/m².
• Patients agree to have one liver biopsy during the screening period for diagnostic purpose (if no historical biopsy within 6 months before randomization is available) and one at the end of the treatment period for assessment of the treatment effects.
• For hypertensive patients, hypertension must be controlled by stable dose of anti-hypertensive medication for at least 2 months prior to screening (and the stable dose can be maintained throughout the study).
• Patients treated with vitamin E (>400IU/d), or Polyunsaturated fatty acids (>2g/day)or Ursodeoxycholic acid can be included if drugs are stopped at least 3 months prior to diagnostic liver biopsy and up to the end of the study.
• Histological confirmation of steatohepatitis on a diagnostic liver biopsy. Histological diagnostic is confirmed by central reading of the slides (steatosis > 5% + lobular inflammation, any grade + ballooning, any amount).
• For patients with Type 2 Diabetes, glycemia must be controlled (Glycosylated Haemoglobin A1c ≤8.5%). If glycemia is controlled by anti-diabetic drugs, qualitative change is not permitted within 6 months prior to randomization and should be avoided during the study. Treatments with metformin, Dipeptidyl Peptidase 4 inhibitors, Glucagon-like peptide-1 agonists, sulfamides, insulin are authorized. Sulfamides and insulin are permitted if glycemia is self-monitored by the patient.

Exclusion Criteria

• Known heart failure (Grade I to IV of New York Heart Association classification).
• Weight loss of more than 5% within 6 months prior to randomization.
• History of bariatric surgery.
• Uncontrolled Blood Pressure.
• Type 1 diabetes patients.
• Patients who had an acute cardiovascular episode within the 6 months prior to screening, or with a history of coronary angioplasty, history of stroke, Transient Ischemic Attack, Coronary Heart Disease.
• Compensated and uncompensated cirrhosis. Notably, NASH patients with fibrosis stage = 4 according to the NASH CRN fibrosis staging system are excluded.
• Known alcohol and/or any other drug abuse or dependence in the last five years.
• Pregnant or lactating females.
• Other well documented causes of chronic liver disease
• Known intolerance or contra-indication to the list of excipients of GFT505.
• Evidence of any other unstable or, untreated clinically significant immunological, neoplastic, endocrine, haematological, gastrointestinal, neurological or psychiatric disorder.
• Positive HBsAg (Hepatitis B Surface Antigen), Positive anti-HIV, positive HCV-RNA (Hepatitis C Virus).
• Uncontrolled hypothyroidism defined as Thyroid Stimulating Hormone > 2X the upper limit of normal (ULN). Thyroid dysfunction controlled for at least 6 months prior to screening is permitted.
• Significant renal disease, including nephritic syndrome, chronic renal failure (defined as creatinine clearance < 60 mL/mn and serum creatinine >180 μmol/L).
• Unexplained serum creatine phosphokinase (CPK) > 3X the upper limit of normal (ULN). Patients with a reason for CPK elevation may have the measurement repeated prior to randomization; a CPK retest > 3X ULN leads to exclusion.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Naturalpha

INDUSTRY

Sponsor Role: collaborator

Premier Research Group plc

UNKNOWN

Sponsor Role: collaborator

Genfit

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rémy HANF, PhD

Role: STUDY_DIRECTOR

Development Director Genfit, France

Pr. Vlad RATZIU, M.D.

Role: STUDY_CHAIR

International Coordinator - La Pitié-Salpêtrière Hospital - Paris 13, France

Pr. Arun SANYAL, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Coordinator -Virginia Commonwealth University - Richmond - USA

Dr. Sven FRANCQUE, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Coordinator - UZA - Edegem - Belgium

Dr. Jost PH DRENTH, MD, Ph.D

Role: PRINCIPAL_INVESTIGATOR

National Coordinator - UMC St Radboud Nijmegen - Nijmegen - The Netherlands

Pr. Michael Manns, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Coordinator - Medical School of Hannover - Hannover - Germany

Pr. Elisabetha BUGIANESI, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Coordinator - University of Torino - S. Giovanni Battista Hospital - Torino - Italy

Pr. Mihai VOICULESCU, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Coordinator - Center of Internal Medicine, Fundeni Clinical Institute - Bucharest - Romania

Pr. Manuel ROMERO-GOMEZ, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Coordinator - Valme University hospital - Sevilla - Spain

Pr. Quentin M. ANSTEE, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Coordinator - Freeman Hospital - Newcastle - UK

Locations

Site 920

Fresno, California, United States

Site 903

La Jolla, California, United States

Site 911

Aurora, Colorado, United States

Site 912

Gainesville, Florida, United States

Site 924

Atlanta, Georgia, United States

Site 917

Atlanta, Georgia, United States

Site 909

New Orleans, Louisiana, United States

Site 921

Worcester, Massachusetts, United States

Site 902

Detroit, Michigan, United States

Site 927

New York, New York, United States

Site 908

Durham, North Carolina, United States

Site 919

Philadelphia, Pennsylvania, United States

Site 916

Memphis, Tennessee, United States

Site 913

Fort Sam Houston, Texas, United States

Site 923

Houston, Texas, United States

Site 906

San Antonio, Texas, United States

Site 931

Salt Lake City, Utah, United States

Site 930

Charlottesville, Virginia, United States

Site 901

Richmond, Virginia, United States

Site 205

Brussels, , Belgium

Site 201

Edegem, , Belgium

Site 204

Ghent, , Belgium

Site 202

Haine-Saint-Paul, , Belgium

Site 203

Leuven, , Belgium

Site 106

Amiens, , France

Site 102

Angers, , France

Site 114

Clichy, , France

Site 103

Lille, , France

Site 113

Lyon, , France

Site 111

Marseille, , France

Site 108

Montpellier, , France

Site 104

Nantes, , France

Site 109

Nice, , France

Site 112

Paris, , France

Site 101

Paris, , France

Site 107

Pessac, , France

Site 405

Bonn, , Germany

Site 404

Mainz, , Germany

Site 507

Milan, , Italy

Site 503

Palermo, , Italy

Site 504

Roma, , Italy

Site 501

Torino, , Italy

Site 303

Amsterdam, , Netherlands

Site 302

Nijmegen, , Netherlands

Site 603

Bucharest, , Romania

Site 601

Bucharest, , Romania

Site 602

Bucharest, , Romania

Site 703

Barcelona, , Spain

Site 707

Majadahonda, , Spain

Site 705

Málaga, , Spain

Site 706

Santander, , Spain

Site 701

Seville, , Spain

Site 802

Camberley, , United Kingdom

Site 808

Hull, , United Kingdom

Site 801

Newcastle upon Tyne, , United Kingdom

Site 803

Nottingham, , United Kingdom

Countries

United States; Belgium; France; Germany; Italy; Netherlands; Romania; Spain; United Kingdom

References

Ratziu V, Harrison SA, Francque S, Bedossa P, Lehert P, Serfaty L, Romero-Gomez M, Boursier J, Abdelmalek M, Caldwell S, Drenth J, Anstee QM, Hum D, Hanf R, Roudot A, Megnien S, Staels B, Sanyal A; GOLDEN-505 Investigator Study Group. Elafibranor, an Agonist of the Peroxisome Proliferator-Activated Receptor-alpha and -delta, Induces Resolution of Nonalcoholic Steatohepatitis Without Fibrosis Worsening. Gastroenterology. 2016 May;150(5):1147-1159.e5. doi: 10.1053/j.gastro.2016.01.038. Epub 2016 Feb 11.

Reference Type: DERIVED

PMID: 26874076 (View on PubMed)

Other Identifiers

2012-000295-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GFT505-212-7

Identifier Type: -

Identifier Source: org_study_id