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A Study to Evaluate the Efficacy and Safety of GFT505 Once Daily on Steatohepatitis in Patients With Non-Alcoholic Steatohepatitis (NASH). A Multicentre, Randomized, Double Blind, Placebo-Controlled Study, With an Adaptive Design to Allow for Initial GFT505 80mg Dosing Versus Placebo, Followed by a Second Phase Including GFT505 120mg Dose, After Review of 6-month Safety Analysis of the 80mg Data on at Least 50% of Patients.


Phase 2
18 Years
75 Years
Open (Enrolling)
Both
Non-Alcoholic Steatohepatitis (NASH)

Thank you

Trial Information

A Study to Evaluate the Efficacy and Safety of GFT505 Once Daily on Steatohepatitis in Patients With Non-Alcoholic Steatohepatitis (NASH). A Multicentre, Randomized, Double Blind, Placebo-Controlled Study, With an Adaptive Design to Allow for Initial GFT505 80mg Dosing Versus Placebo, Followed by a Second Phase Including GFT505 120mg Dose, After Review of 6-month Safety Analysis of the 80mg Data on at Least 50% of Patients.


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.


Inclusion Criteria:



- Males or females (females must be either of non-child bearing potential or using an
efficient double contraception).

- 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 authorised. 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,
neoplasic, 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.

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Outcome Measure:

Percentage of responders defined by the disappearance of steatohepatitis without worsening of fibrosis

Outcome Description:

To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg, the percentage of responders from baseline to Week 52, defined by the disappearance of steatohepatitis (i.e. patients no longer meeting the criteria for steatohepatitis) without worsening of fibrosis. Worsening of fibrosis is evaluated using NASH CRN (Clinical Research Network) fibrosis staging system and defined as: Progression to stage 3 or 4 for patients at stage 0, 1 or 2 on diagnostic liver biopsy Progression to stage 4 for patients at stage 3 on diagnostic liver biopsy

Outcome Time Frame:

52 weeks

Safety Issue:

Yes

Principal Investigator

Rémy HANF, PhD

Investigator Role:

Study Director

Investigator Affiliation:

Development Director Genfit, France

Authority:

United States: Food and Drug Administration

Study ID:

GFT505-212-7

NCT ID:

NCT01694849

Start Date:

September 2012

Completion Date:

January 2015

Related Keywords:

  • Non-Alcoholic Steatohepatitis (NASH)
  • PPARs
  • NASH
  • Non-Alcoholic Steatohepatitis
  • Liver Diseases
  • Fibrosis
  • Fatty Liver

Name

Location

Site 920Fresno, California  CA 9372
Site 903La Jolla, California  CA 92037
Site 911Aurora, Colorado  CO 80045
Site 912Gainesville, Florida  FL 32610-0277
Site 909New Orleans, Louisiana  LA 70112-2600
Site 902Detroit, Michigan  MI 48202
Site 922St. Louis, Missouri  MO 63110
Site 908Durham, North Carolina  NC 27710
Site 919Philadelphia, Pennsylvania  PA 19104
Site 925Charleston, South Carolina  SC 29425
Site 913Fort Sam Houston, Texas  TX 78234
Site 923Houston, Texas  TX 77030
Site 906San Antonio, Texas  TX 78215
Site 901Richmond, Virginia  VA 23298