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

NCT01694849 | Completed Phase 2 Results DMC

• 2 other identifiers: GFT505-212-72012-000295-42
• Study Type: interventional
• Target: 275
• Locations: 9 countries
• Sites: 56

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.

Conditions

Non-Alcoholic Steatohepatitis (NASH)

Keywords

PPARs; NASH; Non-Alcoholic Steatohepatitis; Liver Diseases; Fibrosis

Outcome Measures

Primary Outcomes (1)

• Percentage of Responders With Disappearance of Steatohepatitis Without Worsening of Fibrosis (ie, Participants no Longer Meeting the Criteria for Steatohepatitis)

  Percentage of responders from baseline to Week 52 defined by the disappearance of steatohepatitis (ie, participants no longer meeting the criteria for steatohepatitis) without worsening of fibrosis. Worsening of fibrosis was evaluated using Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) fibrosis staging system and defined as: * Progression to stage 3 or 4 for participants at stage 0, 1 or 2 on diagnostic liver biopsy * Progression to stage 4 for participants at stage 3 on diagnostic liver biopsy

  Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

Secondary Outcomes (47)

• Change From Baseline to Week 52 in Non-alcoholic Fatty Liver Disease Activity Score

  Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

• Number of Participants With Change From Baseline to Week 52 in Non-alcoholic Fatty Liver Disease Activity Score of at Least 2 Points

  Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

• Number of Participants With Decrease in Steatosis Score of at Least 1 Point Between Baseline and Week 52

  Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

• Number of Participants With Decrease in Lobular Inflammation Score of at Least 1 Point Between Baseline and Week 52

  Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

• Title: Number of Participants With Decrease in Ballooning Score of at Least 1 Point Between Baseline and Week 52

  Baseline (Visit 2; Week 0) to Visit 8 (Week 52)

Study Arms (3)

GFT505 80mg

EXPERIMENTAL

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

Drug: GFT505 80mg

GFT505 120mg

EXPERIMENTAL

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

Drug: GFT505 120mg

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

GFT505 80mg DRUG

GFT505 80mg

GFT505 120mg DRUG

GFT505 120mg

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Genfit: lead
• Naturalpha: collaborator
• Premier Research: collaborator

Study Sites (56)

Site 920

Fresno, California, CA 9372, United States

Location

Site 903

La Jolla, California, CA 92037, United States

Location

Site 911

Aurora, Colorado, CO 80045, United States

Location

Site 912

Gainesville, Florida, FL 32610-0277, United States

Location

Site 924

Atlanta, Georgia, GA 30303, United States

Location

Site 917

Atlanta, Georgia, GA 30322, United States

Location

Site 909

New Orleans, Louisiana, LA 70112-2600, United States

Location

Site 921

Worcester, Massachusetts, MA 01655, United States

Location

Site 902

Detroit, Michigan, MI 48202, United States

Location

Site 927

New York, New York, NY 10029-6574, United States

Location

Site 908

Durham, North Carolina, NC 27710, United States

Location

Site 919

Philadelphia, Pennsylvania, PA 19104, United States

Location

Site 916

Memphis, Tennessee, TN 38104, United States

Location

Site 913

Fort Sam Houston, Texas, TX 78234, United States

Location

Site 923

Houston, Texas, TX 77030, United States

Location

Site 906

San Antonio, Texas, TX 78215, United States

Location

Site 931

Salt Lake City, Utah, UT 84132, United States

Location

Site 930

Charlottesville, Virginia, VA 22908, United States

Location

Site 901

Richmond, Virginia, VA 23298, United States

Location

Site 205

Brussels, 1070, Belgium

Location

Site 201

Edegem, B-2650, Belgium

Location

Site 204

Ghent, B-9000, Belgium

Location

Site 202

Haine-Saint-Paul, 7100, Belgium

Location

Site 203

Leuven, 3000, Belgium

Location

Site 106

Amiens, 80054, France

Location

Site 102

Angers, 49933, France

Location

Site 114

Clichy, 92110, France

Location

Site 103

Lille, 59037, France

Location

Site 113

Lyon, 69317, France

Location

Site 111

Marseille, 13285, France

Location

Site 108

Montpellier, 34295, France

Location

Site 104

Nantes, 44093, France

Location

Site 109

Nice, 06202, France

Location

Site 112

Paris, 75571, France

Location

Site 101

Paris, 75651, France

Location

Site 107

Pessac, 33604, France

Location

Site 405

Bonn, 53127, Germany

Location

Site 404

Mainz, 55131, Germany

Location

Site 507

Milan, 20122, Italy

Location

Site 503

Palermo, 90127, Italy

Location

Site 504

Roma, 00133, Italy

Location

Site 501

Torino, 10126, Italy

Location

Site 303

Amsterdam, 1100, Netherlands

Location

Site 302

Nijmegen, 6500, Netherlands

Location

Site 603

Bucharest, 021105, Romania

Location

Site 601

Bucharest, 022328, Romania

Location

Site 602

Bucharest, 022328, Romania

Location

Site 703

Barcelona, 08036, Spain

Location

Site 707

Majadahonda, 28222, Spain

Location

Site 705

Málaga, 29010, Spain

Location

Site 706

Santander, 39008, Spain

Location

Site 701

Seville, 41014, Spain

Location

Site 802

Camberley, GU16 7UJ, United Kingdom

Location

Site 808

Hull, HU3 2JZ, United Kingdom

Location

Site 801

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Site 803

Nottingham, NG7 2UH, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 26874076 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Liver Diseases; Fibrosis

Interventions

2-(2,6-dimethyl-4-(3-(4-(methylthio)phenyl)-3-oxo-1-propenyl)phenoxyl)-2-methylpropanoic acid

Condition Hierarchy (Ancestors)

Fatty Liver; Digestive System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Carol Addy, MD MMSc
• Organization: GENFIT

+01 6179536469

Study Officials

• Rémy HANF, PhD

  Development Director Genfit, France

  STUDY DIRECTOR

• Pr. Vlad RATZIU, M.D.

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

  STUDY CHAIR

• Pr. Arun SANYAL, M.D.

  National Coordinator -Virginia Commonwealth University - Richmond - USA

  PRINCIPAL INVESTIGATOR

• Dr. Sven FRANCQUE, M.D.

  National Coordinator - UZA - Edegem - Belgium

  PRINCIPAL INVESTIGATOR

• Dr. Jost PH DRENTH, MD, Ph.D

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

  PRINCIPAL INVESTIGATOR

• Pr. Michael Manns, M.D.

  National Coordinator - Medical School of Hannover - Hannover - Germany

  PRINCIPAL INVESTIGATOR

• Pr. Elisabetha BUGIANESI, M.D.

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

  PRINCIPAL INVESTIGATOR

• Pr. Mihai VOICULESCU, M.D.

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

  PRINCIPAL INVESTIGATOR

• Pr. Manuel ROMERO-GOMEZ, M.D.

  National Coordinator - Valme University hospital - Sevilla - Spain

  PRINCIPAL INVESTIGATOR

• Pr. Quentin M. ANSTEE, M.D.

  National Coordinator - Freeman Hospital - Newcastle - UK

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2012
• First Posted: September 27, 2012
• Study Start: September 1, 2012
• Primary Completion: February 1, 2015
• Study Completion: December 1, 2015
• Last Updated: November 3, 2022
• Results First Posted: November 3, 2022

Record last verified: 2022-11

Locations

DE (2); FR (12); US (19); IT (4); NL (2); RO (3); ES (5); GB (4); BE (5)