Non-Alcoholic Steatohepatitis (NASH)Phase 2NCT01694849
Phase IIb Study to Evaluate the Efficacy and Safety of GFT505 Versus Placebo in Patients With Non-Alcoholic Steatohepatitis (NASH)
A Phase 2 study testing GFT505 80mg and GFT505 120mg in people with Non-Alcoholic Steatohepatitis (NASH), run by Genfit at 56 sites in 9 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Non-Alcoholic Steatohepatitis (NASH)
- What is being tested?
- GFT505 80mg and GFT505 120mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 275 participants
- Where
- 56 sitesin 9 countries
- Study dates
- Sep 2012to Dec 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 16Show fewer
- 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.
Trial locations and contacts
56 sites in 9 countries.
56 sites in 9 countries
United States19 sites
Site 924
Atlanta, Georgia, GA 30303
Site 917
Atlanta, Georgia, GA 30322
Site 911
Aurora, Colorado, CO 80045
Site 930
Charlottesville, Virginia, VA 22908
Site 902
Detroit, Michigan, MI 48202
Site 908
Durham, North Carolina, NC 27710
Site 913
Fort Sam Houston, Texas, TX 78234
Site 920
Fresno, California, CA 9372
Site 912
Gainesville, Florida, FL 32610-0277
Site 923
Houston, Texas, TX 77030
Site 903
La Jolla, California, CA 92037
Site 916
Memphis, Tennessee, TN 38104
Site 909
New Orleans, Louisiana, LA 70112-2600
Site 927
New York, New York, NY 10029-6574
Site 919
Philadelphia, Pennsylvania, PA 19104
Site 901
Richmond, Virginia, VA 23298
Site 931
Salt Lake City, Utah, UT 84132
Site 906
San Antonio, Texas, TX 78215
Site 921
Worcester, Massachusetts, MA 01655
France12 sites
Site 106
Amiens, 80054
Site 102
Angers, 49933
Site 114
Clichy, 92110
Site 103
Lille, 59037
Site 113
Lyon, 69317
Site 111
Marseille, 13285
Site 108
Montpellier, 34295
Site 104
Nantes, 44093
Site 109
Nice, 06202
Site 112
Paris, 75571
Site 101
Paris, 75651
Site 107
Pessac, 33604
Belgium5 sites
Site 205
Brussels, 1070
Site 201
Edegem, B-2650
Site 204
Ghent, B-9000
Site 202
Haine-Saint-Paul, 7100
Site 203
Leuven, 3000
Spain5 sites
Site 703
Barcelona, 08036
Site 707
Majadahonda, 28222
Site 705
Málaga, 29010
Site 706
Santander, 39008
Site 701
Seville, 41014
Italy4 sites
Site 507
Milan, 20122
Site 503
Palermo, 90127
Site 504
Roma, 00133
Site 501
Torino, 10126
United Kingdom4 sites
Site 802
Camberley, GU16 7UJ
Site 808
Hull, HU3 2JZ
Site 801
Newcastle upon Tyne, NE7 7DN
Site 803
Nottingham, NG7 2UH
Romania3 sites
Site 603
Bucharest, 021105
Site 601
Bucharest, 022328
Site 602
Bucharest, 022328
About this study
Official title: A Multicentre, Randomized, Double Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of GFT505 Once Daily on Steatohepatitis in Patients With Non-Alcoholic Steatohepatitis (NASH).
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.
Read more
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.
Read the 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)
- Being tested
- GFT505 80mg, GFT505 120mg, Placebo
- Keywords
- PPARs, NASH, Non-Alcoholic Steatohepatitis, Liver Diseases, Fibrosis
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Liver Diseases, Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GFT505 80mgDrug
GFT505 120mgDrug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| GFT505 80mg | Experimental | Hard gelatin capsules dosed at 40mg, oral administration, 3 capsules per day before breakfast with a glass of water. Receives: 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. Receives: Drug: GFT505 120mg |
| Placebo | Placebo comparator | hard gelatin capsules, oral administration, 3 capsules per day before breakfast with a glass of water. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg the change from baseline to Week 52, in Non-alcoholic Fatty Liver Disease Activity Score (NAS score).
NAS score is a composite score equal to the sum of the steatosis grade (0 to 3), lobular inflammation grade (0 to 3) and hepatocellular ballooning grade (0 to 2). The overall scale of the NAS is 0 to 8, with higher scores indicating more severe disease. The outcome measure, change from baseline in NAFLD Activity Score (NAS), has a possible range from -8 to +8, with negative values indicating a better outcome (improvement) and positive values indicating a worse outcome.
Measured: 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
To evaluate the number of participants with at least a 2 point decrease from baseline in Non-alcoholic Fatty Liver Disease Activity Score (NAS) after 52 weeks of daily administration of GFT505 80mg or 120mg. The NAS refers to the severity of ongoing liver injury as assessed by a liver biopsy and is used to assess the activity of the disease. It is based on the NASH CRN methodology for scoring the severity of steatosis (score of 0 to 3), inflammation (score of 0 to 3), and hepatocellular ballooning (score of 0 to 2), with a maximum score of 8. A total NAS score of five or greater correlates with the diagnosis of steatohepatitis.
In table below for raw "Mild (Nonalcoholic Fatty Liver Disease Activity Score 3)" and the column "GFT505 80mg" the result should be read as : 2 participants (out of 10 participants analysed with a baseline NAS at 3) had at Least 2 points decrease on their NAS after 52 weeks of daily administration of GFT505 80mg. It corresponds to 20% (2 out of 10).
Measured: 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
To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg, number of participants with a decrease in steatosis score of at least 1 point between baseline and Week 52.
Steatosis is assessed by a liver biopsy and evaluated on a scale of 0 to 3 with higher scores indicating more severe steatosis. A score of 0 indicating a lower severity with low parenchymal involvement (<5%), while a score of 3 is indicative of higher involvment/severity (> 66%).
In below table and for helping how results are reported, as an example for raw "Mild (Nonalcoholic Fatty Liver Disease Activity Score 3)" and the column "GFT505 80mg" the result should be read as : 1 participants (out of 10 participants analysed with a baseline NAS at 3) had at least 1 point decrease Steatosis Score after 52 weeks of daily administration of GFT505 80mg. It corresponds to 10% (1 out of 10).
Measured: 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
To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg, number of participants with a decrease in lobular inflammation score of at least 1 point between baseline and Week 52.
Lobular inflammation is assessed by a liver biopsy and evaluated on a scale of 0 to 3. A score of 0 indicating the absence of inflammation loci, while a score of 3 is indicative of a higher degree of inflammation with more than 4 inflammation loci 200 x field.
In below table and for helping how results are reported, as an example for raw "Mild (Nonalcoholic Fatty Liver Disease Activity Score 3)" and the column "GFT505 80mg" the result should be read as : 1 participants (out of 10 participants analysed with a baseline NAS at 3) had at least 1 point decrease of Lobular Inflammation Score after 52 weeks of daily administration of GFT505 80mg. It corresponds to 10% (1 out of 10).
Measured: 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
To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg, number of participants with a decrease in ballooning score of at least 1 point between baseline and Week 52.
Ballooning is assessed by a liver biopsy and evaluated on a scale of 0 to 2 with higher scores indicating more severe ballooning (0: No ballooned cells, 1: Few [rare but definite] ballooned hepatocytes; 2: Many ballooned cells/prominent ballooning).
In below table and for helping how results are reported, as an example for raw "Mild (Nonalcoholic Fatty Liver Disease Activity Score 3)" and the column "GFT505 80mg" the result should be read as : 4 participants (out of 10 participants analysed with a baseline NAS at 3) had at least 1 point decrease of Ballooning Score after 52 weeks of daily administration of GFT505 80mg. It corresponds to 10% (1 out of 10).
Measured: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in the Stages of Fibrosis
To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg, the changes from baseline to Week 52, in stages of fibrosis (based on Non-Alcoholic Steatohepatitis Clinical Research Network [NASH CRN] scoring).
Fibrosis is assessed on a scale of 0 to 4 with higher scores indicating more severe fibrosis.
Measured: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Visit 8 (Week 52) in Liver Enzymes
To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg the changes from baseline to week 52, in liver enzymes.
Measured: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Visit 8 (Week 52) in Aspartate Transaminase/Alanine Aminotransferase Ratio
To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg the changes from baseline to week 52, in aspartate transaminase/alanine aminotransferase ratio
Measured: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: CK 18-M65
To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg, the changes from baseline to week 52, in CK 18-M65 (non-invasive markers of fibrosis and steatosis).
Measured: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: CK18 M30
To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg, the changes from baseline to week 52, in CK18 M30 (non-invasive markers of fibrosis and steatosis).
Participants with missing data for CK18 M30 at baseline (Visit 2) or Visit 8 were not imputed in the analysis explaining the difference with the number of participants reported in the "Efficacy Evaluable Set" of the Participant Flow.
Measured: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Adiponectin
To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg, the changes from baseline to week 52, in adiponectin (non-invasive markers of fibrosis and steatosis).
Measured: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Ferritin
To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg, the changes from baseline to week 52, in ferritin (non-invasive markers of fibrosis and steatosis).
Participants with missing data for Ferritin at baseline (Visit 2) or Visit 8 were not imputed in the analysis explaining the difference with the number of participants reported in the "Efficacy Evaluable Set" of the Participant Flow.
Measured: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: FG19 and FG21
To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg, the changes from baseline to week 52, in FG19 and FG21 (non-invasive markers of fibrosis and steatosis).
Measured: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Alpha2 Macroglobulin
To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg, the changes from baseline to week 52, in alpha2 macroglobulin (a non-invasive marker of fibrosis and steatosis).
Participants with missing data for Alpha2 Macroglobulin at baseline (Visit 2) or Visit 8 were not imputed in the analysis explaining the difference with the number of participants reported in the "Efficacy Evaluable Set" of the Participant Flow.
Measured: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Hyaluronic Acid, N-terminal Pro-peptide of Collagen Type III (PIIINP), and Tissue Inhibitor of Matrix Metalloprotease-1 (TIMP-1)
To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg, the changes from baseline to week 52, in hyaluronic acid, N-terminal pro-peptide of collagen type III (PIIINP), and tissue inhibitor of matrix metalloprotease-1 (TIMP-1) (non-invasive markers of fibrosis and steatosis).
Measured: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Fibrotest
Fibrotest combines α2-macroglobulin (a2m), apolipoprotein A1 (aA1), total bilirubin (BIL), haptoglobin (h), GGT, and ALT with adjustment for age and gender. Fibrotest is calculated as: z = 4.467 x log(a2m) - 1.357 x log(h) + 1.017 x log(GGT) + 0.0281 x Age + 1.737 x log(BIL) - 1.184 x (aA1) + 0.301 x Gender - 5.54 where Gender = 1 for male and Gender = 0 for female. The score is then: 1/(1+e^-z). Calculated score range from 0 (no fibrosis) to 1 (severe fibrosis or cirrhosis) In below table for "Fibrotest" and for column "GFT505 80mg" the result should be read as: the mean of change from baseline to week 52 of Fibrotest calculated in 81 participants is -0.06 with a standard deviation of 0.08.
Measured: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Steatotest
SteatoTest combines α2-macroglobulin, haptoglobin, apolipoprotein A1, total bilirubin, GGT, fasting glucose, triglycerides, cholesterol, and ALT, adjusted for patient's age, sex, weight, and height. Patented formula. Calculated score range from 0 (no steatosis) to 1 (severe steatosis) In below table for "Steatotest" and for column "GFT505 80mg" the result should be read as: the mean of change from baseline to week 52 of Steatotest calculated in 81 participants is -0.09 with a standard deviation of 0.11.
Measured: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Angulo Index or Non-Alcoholic Fatty Liver Disease Fibrosis Score
Angulo Index or Non-Alcoholic Fatty Liver Disease Fibrosis Score is based on age, hyperglycemia, BMI, platelet count, albumin level, and AST/ALT ratio. Score is calculated using the following formula: -1.675 + 0.037 × age (years) + 0.094 × BMI (kg/m^2) + 1.13 × IFG/diabetes (yes = 1, no = 0) + 0.99 × AST/ALT ratio - 0.013 × platelet (×10^9/l) - 0.66 × albumin (g/dl). A score of <-1.455 indicates no advanced fibrosis and a score of >0.676 indicates liver fibrosis.
In below table for "Angulo index" and for column "GFT505 80mg" the result should be read as: the mean of change from baseline to week 52 of Angulo index calculated in 82 participants is 0.06 with a standard deviation of 0.53.
Measured: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Enhanced Liver Fibrosis (ELF)
Enhanced Liver Fibrosis (ELF) combines measurements of tissue inhibitor of metalloprotein-ases-1 (TIMP-1), amino-terminal propeptide of type III procollagen (PIIINP), and hyaluronic acid (HA) . The ELF score is calculated as : 2.278 + 0.851 ln (HA) + 0.751 ln (PIIINP) + 0.394 ln (TIMP-1). ELF score range from An ELF score of less than 7.7 indicates no fibrosis. An ELF score greater than or equal to 9.8 indicates severe fibrosis. An ELF score of 11.3 or greater indicates cirrhosis. A decrease in ELF score represents a positive outcome In below table for "Enhanced Liver Fibrosis" and for column "GFT505 80mg" the result should be read as : the mean of change from baseline to week 52 of Enhanced Liver Fibrosis calculated in 81 analysed participants is -0.01 with a standard deviation of 0.54.
Measured: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Fatty Liver Index (FLI)
The Fatty Liver Index (FLI) combines triglycerides, BMI, GGT and Waist circumference. FLI is calculated as : (e0.953×loge[triglycerides]+0.139× Body Mass Index[BMI]+0.718×loge Gamma- Glutamyl Transferase [GGT]+0.053×waistcircumference-15.745)/ (1 +e0.953×loge[triglycerides]+0.139×BMI+0.718×loge [GGT]+0.053×waistcircumference-15.745) × 100. Calculated index range from 0 to 100. FLI score below 30 indicate absence of Fatty Liver and FLI Score of 60 and above indicates presence of Fatty Liver.
In below table for "Fatty Liver Index" and for column "GFT505 80mg" the result should be read as : the mean of change from baseline to week 52 of Fatty Liver Index calculated in 82 analysed participants is -7.94 with a standard deviation of 11.74.
Measured: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Fibrometer
Fibrometer combines Platelets, AST, ALT, ferritin, glucose (fasting plasma), Weight and gender. Patented formula. Score ranges from 0 (no fibrosis) to 1 (severe fibrosis or cirrhosis) In below table for "Fibrometer" and for column "GFT505 80mg" the result should be read as : the mean of change from baseline to week 52 of Fibrometer calculated in 81 analysed participants is 0.04 with a standard deviation of 0.23.
Measured: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Total Bilirubin and Conjugated Bilirubin
To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg, the changes from baseline to week 52, in total bilirubin and conjugated bilirubin (non-invasive markers of fibrosis and steatosis).
Measured: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Prothrombin Ratio
To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg, the changes from baseline to week 52, in prothrombin ratio (non-invasive marker of fibrosis and steatosis).
The Prothrombin ratio is the ratio of a participants measured prothrombin time (in seconds) to the normal laboratory reference prothrombin time.
Participants with missing data for Prothrombin ratio at baseline (Visit 2) or Visit 8 were not imputed in the analysis explaining the difference with the number of participants reported in the "Efficacy Evaluable Set" of the Participant Flow.
Measured: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: International Normalized Ratio (INR)
To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg, the changes from baseline to week 52, in international normalized ratio (INR; non-invasive marker of fibrosis and steatosis).
Participants with missing data for International Normalized Ratio (INR) at baseline (Visit 2) or Visit 8 were not imputed in the analysis explaining the difference with the number of participants reported in the "Efficacy Evaluable Set" of the Participant Flow.
Measured: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Lipid Parameters (Cardiovascular Risk Profile)
To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg the changes from baseline to week 52, in lipid parameters (used to assess cardiovascular risk)
Measured: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Outcomes Related to Biochemistry
To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg the changes from baseline to week 52, in secondary outcomes related to biochemistry
Measured: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Insulin Resistance: Leptin
To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg, the changes from baseline to Week 52, in leptin (to assess insulin resistance).
Measured: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Insulin Resistance: Insulin
To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg, the changes from baseline to Week 52, in insulin (to assess insulin resistance).
Participants with missing data for Insulin at baseline (Visit 2) or Visit 8 were not imputed in the analysis explaining the difference with the number of participants reported in the "Efficacy Evaluable Set" of the Participant Flow.
Measured: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Insulin Resistance: C Peptide
To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg, the changes from baseline to Week 52, in C peptide (to assess insulin resistance).
Participants with missing data for C Peptide at baseline (Visit 2) or Visit 8 were not imputed in the analysis explaining the difference with the number of participants reported in the "Efficacy Evaluable Set" of the Participant Flow.
Measured: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Insulin Resistance: Homeostatic Model Assessment-insulin Resistance (HOMA-IR)
To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg, the changes from baseline to Week 52, in homeostatic model assessment-insulin resistance (HOMA-IR; to assess insulin resistance).
The HOMA-IR is expressed as the following: HOMA-IR = fasting serum insulin (μU/ml) x fasting plasma glucose (mmol/l) / 22.5
A decrease in HOMA-IR indicates a positive outcome. HOMA-IR values of greater than 1.9 indicates early insulin resistance and levels above 2.9 indicate significant insulin resistance.
Participants with missing data for HOMA-IR at baseline (Visit 2) or Visit 8 were not imputed in the analysis explaining the difference with the number of participants reported in the "Efficacy Evaluable Set" of the Participant Flow.
Measured: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Insulin Resistance: Free Fatty Acids (FFA)
To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg, the changes from baseline to Week 52, in free fatty acids (FFA; to assess insulin resistance).
Participants with missing data for Free Fatty Acids (FFA) at baseline (Visit 2) or Visit 8 were not imputed in the analysis explaining the difference with the number of participants reported in the "Efficacy Evaluable Set" of the Participant Flow.
Measured: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Insulin Resistance: Plasma Glucose
To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg, the changes from baseline to Week 52, in plasma glucose (to assess insulin resistance).
Participants with missing data for Plasma Glucose at baseline (Visit 2) or Visit 8 were not imputed in the analysis explaining the difference with the number of participants reported in the "Efficacy Evaluable Set" of the Participant Flow.
Measured: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Insulin Resistance: Glycosylated Haemoglobin A1c (HbA1c)
To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg, the changes from baseline to Week 52, in glycosylated haemoglobin A1c (HbA1c; to assess insulin resistance).
Participants with missing data for Haemoglobin A1c (HbA1c) at baseline (Visit 2) or Visit 8 were not imputed in the analysis explaining the difference with the number of participants reported in the "Efficacy Evaluable Set" of the Participant Flow.
Measured: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Insulin Resistance: Fructosamine
To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg, the changes from baseline to Week 52, in Fructosamine (to assess insulin resistance).
Measured: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Inflammatory Markers: Fibrinogen and Haptoglobin
To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg the changes from baseline to Week 52, in fibrinogen and haptoglobin (inflammatory markers).
Measured: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Inflammatory Markers: Tumour Necrosis Factor Alpha and Interleukine 6
To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg the changes from baseline to Week 52, in tumour necrosis factor alpha and interleukine 6 (inflammatory markers).
Measured: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Inflammatory Markers: Plasminogen Activator Inhibitor 1 (PAI-1)
To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg the changes from baseline to Week 52, in plasminogen activator inhibitor 1 (PAI-1; inflammatory marker).
Participants with missing data for Plasminogen Activator Inhibitor 1 (PAI-1) at baseline (Visit 2) or Visit 8 were not imputed in the analysis explaining the difference with the number of participants reported in the "Efficacy Evaluable Set" of the Participant Flow
Measured: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Inflammatory Markers: C-Reactive Protein (CRP)
To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg the changes from baseline to Week 52, in C-Reactive Protein (CRP; inflammatory marker).
Measured: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Safety Markers: Creatinine (Renal Function Parameter)
To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg, the changes from baseline to week 52, in creatinine (safety markers; renal function parameter).
Measured: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Safety Markers: Creatinine Clearance (Renal Function Parameter)
To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg, the changes from baseline to week 52, in creatinine clearance (safety marker; renal function parameter).
Measured: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Safety Markers: Uric Acid (Renal Function Parameter)
To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg, the changes from baseline to week 52, in uric acid (safety marker; renal function parameter).
Measured: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Safety Markers: Blood Urea Nitrogen (BUN; Renal Function Parameter)
To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg, the changes from baseline to week 52, in blood urea nitrogen (BUN; safety marker; renal function parameter).
Measured: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Safety Markers: Cystatin C (Renal Function Parameter)
To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg, the changes from baseline to week 52, in cystatin C (safety marker; renal function parameter).
Participants with missing data for Cystatin C at baseline (Visit 2) or Visit 8 were not imputed in the analysis explaining the difference with the number of participants reported in the "Efficacy Evaluable Set" of the Participant Flow.
Measured: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Safety Markers: Beta2-microglobulin (Renal Function Parameter)
To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg, the changes from baseline to week 52, in beta2-microglobulin (safety marker; renal function parameter).
Participants with missing data for Beta2-microglobulin at baseline (Visit 2) or Visit 8 were not imputed in the analysis explaining the difference with the number of participants reported in the "Efficacy Evaluable Set" of the Participant Flow.
Measured: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Safety Markers: N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP; Cardiac Function Parameter)
To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg, the changes from baseline to week 52, in N-terminal prohormone of brain natriuretic peptide (NT-proBNP; safety marker; cardiac function parameter).
Participants with missing data for NT-proBNP at baseline (Visit 2) or Visit 8 were not imputed in the analysis explaining the difference with the number of participants reported in the "Efficacy Evaluable Set" of the Participant Flow.
Measured: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Safety Markers: Troponin T (Cardiac Function Parameter)
To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg, the changes from baseline to week 52, in troponin T (safety marker; cardiac function parameter).
Participants with missing data for Troponin T at baseline (Visit 2) or Visit 8 were not imputed in the analysis explaining the difference with the number of participants reported in the "Efficacy Evaluable Set" of the Participant Flow.
Measured: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Body Weight
To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg, the changes from baseline to Week 52, in body weight.
Measured: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Sep 2012 (estimated)
- Study startSep 2012
- Primary completionFeb 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non-Alcoholic Steatohepatitis (NASH)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 275 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genfit
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Naturalpha, Premier Research
- Responsible party
- Sponsor
- Investigators
- Rémy HANF, PhD, Study director, Development Director Genfit, FrancePr. Vlad RATZIU, M.D., Study chair, International Coordinator - La Pitié-Salpêtrière Hospital - Paris 13, FrancePr. Arun SANYAL, M.D., Principal investigator, National Coordinator -Virginia Commonwealth University - Richmond - USADr. Sven FRANCQUE, M.D., Principal investigator, National Coordinator - UZA - Edegem - BelgiumDr. Jost PH DRENTH, MD, Ph.D, Principal investigator, National Coordinator - UMC St Radboud Nijmegen - Nijmegen - The NetherlandsPr. Michael Manns, M.D., Principal investigator, National Coordinator - Medical School of Hannover - Hannover - GermanyPr. Elisabetha BUGIANESI, M.D., Principal investigator, National Coordinator - University of Torino - S. Giovanni Battista Hospital - Torino - ItalyPr. Mihai VOICULESCU, M.D., Principal investigator, National Coordinator - Center of Internal Medicine, Fundeni Clinical Institute - Bucharest - Romania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01694849
- Sponsor's protocol ID
- GFT505-212-7
- Other IDs
- 2012-000295-42
- Status last verified
- Nov 2022
- First submitted
- 24 Sep 2012
- Last updated
- 3 Nov 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 26874076
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicentre, Randomized, Double Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of GFT505 Once Daily on Steatohepatitis in Patients With Non-Alcoholic Steatohepatitis (NASH).
- ClinicalTrials.gov ID
- NCT01694849
- Acronym / sponsor ID
- GFT505-212-7
- Conditions
- Non-Alcoholic Steatohepatitis (NASH)
- Keywords
- PPARs, NASH, Non-Alcoholic Steatohepatitis, Liver Diseases, Fibrosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 275 participants (actual)
- Lead sponsor
- GenfitIndustry (pharma, biotech, devices)
- Collaborators
- Naturalpha, Premier Research
- Study start
- Sep 2012
- Primary completion
- Feb 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 27 Sep 2012 (estimated)
- Results
- Posted 3 Nov 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| GFT505 80mg | Experimental | Drug: GFT505 80mgHard gelatin capsules dosed at 40mg, oral administration, 3 capsules per day before breakfast with a glass of water. |
| GFT505 120mg | Experimental | Drug: GFT505 120mgHard gelatin capsules dosed at 40mg, oral administration, 3 capsules per day before breakfast with a glass of water. |
| Placebo | Placebo comparator | Drug: Placebohard gelatin capsules, oral administration, 3 capsules per day before breakfast with a glass of water. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GFT505 80mg | Drug | GFT505 80mg |
| GFT505 120mg | Drug | GFT505 120mg |
| Placebo | Drug | Placebo |
Primary outcome
Percentage of Responders With Disappearance of Steatohepatitis Without Worsening of Fibrosis (ie, Participants no Longer Meeting the Criteria for Steatohepatitis)
Time frame: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
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
47 secondary outcomes
Change From Baseline to Week 52 in Non-alcoholic Fatty Liver Disease Activity Score
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in the Stages of Fibrosis
Time frame: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Visit 8 (Week 52) in Liver Enzymes
Time frame: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Visit 8 (Week 52) in Aspartate Transaminase/Alanine Aminotransferase Ratio
Time frame: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: CK 18-M65
Time frame: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: CK18 M30
Time frame: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Adiponectin
Time frame: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Ferritin
Time frame: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: FG19 and FG21
Time frame: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Alpha2 Macroglobulin
Time frame: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Hyaluronic Acid, N-terminal Pro-peptide of Collagen Type III (PIIINP), and Tissue Inhibitor of Matrix Metalloprotease-1 (TIMP-1)
Time frame: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Fibrotest
Time frame: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Steatotest
Time frame: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Angulo Index or Non-Alcoholic Fatty Liver Disease Fibrosis Score
Time frame: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Enhanced Liver Fibrosis (ELF)
Time frame: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Fatty Liver Index (FLI)
Time frame: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Fibrometer
Time frame: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Total Bilirubin and Conjugated Bilirubin
Time frame: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Prothrombin Ratio
Time frame: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: International Normalized Ratio (INR)
Time frame: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Lipid Parameters (Cardiovascular Risk Profile)
Time frame: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Outcomes Related to Biochemistry
Time frame: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Insulin Resistance: Leptin
Time frame: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Insulin Resistance: Insulin
Time frame: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Insulin Resistance: C Peptide
Time frame: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Insulin Resistance: Homeostatic Model Assessment-insulin Resistance (HOMA-IR)
Time frame: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Insulin Resistance: Free Fatty Acids (FFA)
Time frame: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Insulin Resistance: Plasma Glucose
Time frame: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Insulin Resistance: Glycosylated Haemoglobin A1c (HbA1c)
Time frame: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Insulin Resistance: Fructosamine
Time frame: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Inflammatory Markers: Fibrinogen and Haptoglobin
Time frame: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Inflammatory Markers: Tumour Necrosis Factor Alpha and Interleukine 6
Time frame: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Inflammatory Markers: Plasminogen Activator Inhibitor 1 (PAI-1)
Time frame: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Inflammatory Markers: C-Reactive Protein (CRP)
Time frame: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Safety Markers: Creatinine (Renal Function Parameter)
Time frame: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Changes From Baseline to Week 52 in Safety Markers: Creatinine Clearance (Renal Function Parameter)
Time frame: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26874076Ratziu 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rémy HANF, PhD study director
Development Director Genfit, France
Pr. Vlad RATZIU, M.D. study chair
International Coordinator - La Pitié-Salpêtrière Hospital - Paris 13, France
Pr. Arun SANYAL, M.D. principal investigator
National Coordinator -Virginia Commonwealth University - Richmond - USA
56 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing GFT505 80mg and GFT505 120mg in people with Non-Alcoholic Steatohepatitis (NASH), run by Genfit at 56 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 56 sites in United States, France, Belgium, Spain, Italy and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Nov 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Responders With Disappearance of Steatohepatitis Without Worsening of Fibrosis (ie, Participants no Longer Meeting the Criteria for Steatohepatitis) (time frame: Baseline (Visit 2; Week 0) to Visit 8 (Week 52)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01694849, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2022.