Back to resultsPhase IIb Study to Evaluate the Efficacy and Safety of GFT505 Versus Placebo in Patients With Non-Alcoholic Steatohepatitis (NASH)
Primary Purpose
Non-Alcoholic Steatohepatitis (NASH)
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
GFT505 80mg
GFT505 120mg
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Non-Alcoholic Steatohepatitis (NASH) focused on measuring PPARs, NASH, Non-Alcoholic Steatohepatitis, Liver Diseases, Fibrosis
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.
Sites / Locations
- Site 920
- Site 903
- Site 911
- Site 912
- Site 924
- Site 917
- Site 909
- Site 921
- Site 902
- Site 927
- Site 908
- Site 919
- Site 916
- Site 913
- Site 923
- Site 906
- Site 931
- Site 930
- Site 901
- Site 205
- Site 201
- Site 204
- Site 202
- Site 203
- Site 106
- Site 102
- Site 114
- Site 103
- Site 113
- Site 111
- Site 108
- Site 104
- Site 109
- Site 112
- Site 101
- Site 107
- Site 405
- Site 404
- Site 507
- Site 503
- Site 504
- Site 501
- Site 303
- Site 302
- Site 603
- Site 601
- Site 602
- Site 703
- Site 707
- Site 705
- Site 706
- Site 701
- Site 802
- Site 808
- Site 801
- Site 803
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
GFT505 80mg
GFT505 120mg
Placebo
Arm Description
Hard gelatin capsules dosed at 40mg, oral administration, 3 capsules per day before breakfast with a glass of water.
Hard gelatin capsules dosed at 40mg, oral administration, 3 capsules per day before breakfast with a glass of water.
hard gelatin capsules, oral administration, 3 capsules per day before breakfast with a glass of water.
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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.
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).
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).
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).
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).
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.
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.
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
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).
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.
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).
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.
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).
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.
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).
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.
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.
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.
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.
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.
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.
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).
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.
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.
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)
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
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).
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.
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.
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.
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.
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.
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.
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).
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).
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).
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
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).
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).
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).
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).
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).
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.
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.
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.
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.
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.
Full Information
NCT ID
NCT01694849
First Posted
September 24, 2012
Last Updated
November 2, 2022
Sponsor
Genfit
Collaborators
Naturalpha, Premier Research Group plc
1. Study Identification
Unique Protocol Identification Number
NCT01694849
Brief Title
Phase IIb Study to Evaluate the Efficacy and Safety of GFT505 Versus Placebo in Patients With Non-Alcoholic Steatohepatitis (NASH)
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).
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Completed
Study Start Date
September 2012 (undefined)
Primary Completion Date
February 2015 (Actual)
Study Completion Date
December 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genfit
Collaborators
Naturalpha, Premier Research Group plc
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Alcoholic Steatohepatitis (NASH)
Keywords
PPARs, NASH, Non-Alcoholic Steatohepatitis, Liver Diseases, Fibrosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
275 (Actual)
8. Arms, Groups, and Interventions
Arm Title
GFT505 80mg
Arm Type
Experimental
Arm Description
Hard gelatin capsules dosed at 40mg, oral administration, 3 capsules per day before breakfast with a glass of water.
Arm Title
GFT505 120mg
Arm Type
Experimental
Arm Description
Hard gelatin capsules dosed at 40mg, oral administration, 3 capsules per day before breakfast with a glass of water.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
hard gelatin capsules, oral administration, 3 capsules per day before breakfast with a glass of water.
Intervention Type
Drug
Intervention Name(s)
GFT505 80mg
Intervention Type
Drug
Intervention Name(s)
GFT505 120mg
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Percentage of Responders With Disappearance of Steatohepatitis Without Worsening of Fibrosis (ie, Participants no Longer Meeting the Criteria for Steatohepatitis)
Description
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
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Secondary Outcome Measure Information:
Title
Change From Baseline to Week 52 in Non-alcoholic Fatty Liver Disease Activity Score
Description
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.
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Title
Number of Participants With Change From Baseline to Week 52 in Non-alcoholic Fatty Liver Disease Activity Score of at Least 2 Points
Description
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).
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Title
Number of Participants With Decrease in Steatosis Score of at Least 1 Point Between Baseline and Week 52
Description
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).
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Title
Number of Participants With Decrease in Lobular Inflammation Score of at Least 1 Point Between Baseline and Week 52
Description
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).
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Title
Title: Number of Participants With Decrease in Ballooning Score of at Least 1 Point Between Baseline and Week 52
Description
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).
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Title
Changes From Baseline to Week 52 in the Stages of Fibrosis
Description
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.
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Title
Changes From Baseline to Visit 8 (Week 52) in Liver Enzymes
Description
To evaluate after 52 weeks of daily administration of GFT505 80mg or GFT505 120mg the changes from baseline to week 52, in liver enzymes.
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Title
Changes From Baseline to Visit 8 (Week 52) in Aspartate Transaminase/Alanine Aminotransferase Ratio
Description
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
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Title
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: CK 18-M65
Description
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).
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Title
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: CK18 M30
Description
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.
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Title
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Adiponectin
Description
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).
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Title
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Ferritin
Description
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.
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Title
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: FG19 and FG21
Description
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).
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Title
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Alpha2 Macroglobulin
Description
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.
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Title
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)
Description
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).
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Title
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Fibrotest
Description
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.
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Title
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Steatotest
Description
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.
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Title
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Angulo Index or Non-Alcoholic Fatty Liver Disease Fibrosis Score
Description
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.
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Title
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Enhanced Liver Fibrosis (ELF)
Description
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.
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Title
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Fatty Liver Index (FLI)
Description
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.
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Title
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Fibrometer
Description
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.
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Title
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Total Bilirubin and Conjugated Bilirubin
Description
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).
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Title
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: Prothrombin Ratio
Description
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.
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Title
Changes From Baseline to Week 52 in Non-invasive Markers of Fibrosis and Steatosis: International Normalized Ratio (INR)
Description
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.
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Title
Changes From Baseline to Week 52 in Lipid Parameters (Cardiovascular Risk Profile)
Description
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)
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Title
Changes From Baseline to Week 52 in Outcomes Related to Biochemistry
Description
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
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Title
Changes From Baseline to Week 52 in Insulin Resistance: Leptin
Description
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).
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Title
Changes From Baseline to Week 52 in Insulin Resistance: Insulin
Description
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.
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Title
Changes From Baseline to Week 52 in Insulin Resistance: C Peptide
Description
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.
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Title
Changes From Baseline to Week 52 in Insulin Resistance: Homeostatic Model Assessment-insulin Resistance (HOMA-IR)
Description
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.
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Title
Changes From Baseline to Week 52 in Insulin Resistance: Free Fatty Acids (FFA)
Description
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.
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Title
Changes From Baseline to Week 52 in Insulin Resistance: Plasma Glucose
Description
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.
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Title
Changes From Baseline to Week 52 in Insulin Resistance: Glycosylated Haemoglobin A1c (HbA1c)
Description
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.
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Title
Changes From Baseline to Week 52 in Insulin Resistance: Fructosamine
Description
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).
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Title
Changes From Baseline to Week 52 in Inflammatory Markers: Fibrinogen and Haptoglobin
Description
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).
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Title
Changes From Baseline to Week 52 in Inflammatory Markers: Tumour Necrosis Factor Alpha and Interleukine 6
Description
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).
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Title
Changes From Baseline to Week 52 in Inflammatory Markers: Plasminogen Activator Inhibitor 1 (PAI-1)
Description
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
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Title
Changes From Baseline to Week 52 in Inflammatory Markers: C-Reactive Protein (CRP)
Description
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).
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Title
Changes From Baseline to Week 52 in Safety Markers: Creatinine (Renal Function Parameter)
Description
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).
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Title
Changes From Baseline to Week 52 in Safety Markers: Creatinine Clearance (Renal Function Parameter)
Description
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).
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Title
Changes From Baseline to Week 52 in Safety Markers: Uric Acid (Renal Function Parameter)
Description
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).
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Title
Changes From Baseline to Week 52 in Safety Markers: Blood Urea Nitrogen (BUN; Renal Function Parameter)
Description
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).
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Title
Changes From Baseline to Week 52 in Safety Markers: Cystatin C (Renal Function Parameter)
Description
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.
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Title
Changes From Baseline to Week 52 in Safety Markers: Beta2-microglobulin (Renal Function Parameter)
Description
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.
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Title
Changes From Baseline to Week 52 in Safety Markers: N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP; Cardiac Function Parameter)
Description
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.
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Title
Changes From Baseline to Week 52 in Safety Markers: Troponin T (Cardiac Function Parameter)
Description
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.
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
Title
Changes From Baseline to Week 52 in Body Weight
Description
To evaluate after 52 weeks of daily administration of GFT505 80mg, or GFT505 120mg, the changes from baseline to Week 52, in body weight.
Time Frame
Baseline (Visit 2; Week 0) to Visit 8 (Week 52)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rémy HANF, PhD
Organizational Affiliation
Development Director Genfit, France
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Pr. Vlad RATZIU, M.D.
Organizational Affiliation
International Coordinator - La Pitié-Salpêtrière Hospital - Paris 13, France
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Pr. Arun SANYAL, M.D.
Organizational Affiliation
National Coordinator -Virginia Commonwealth University - Richmond - USA
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Dr. Sven FRANCQUE, M.D.
Organizational Affiliation
National Coordinator - UZA - Edegem - Belgium
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Dr. Jost PH DRENTH, MD, Ph.D
Organizational Affiliation
National Coordinator - UMC St Radboud Nijmegen - Nijmegen - The Netherlands
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Pr. Michael Manns, M.D.
Organizational Affiliation
National Coordinator - Medical School of Hannover - Hannover - Germany
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Pr. Elisabetha BUGIANESI, M.D.
Organizational Affiliation
National Coordinator - University of Torino - S. Giovanni Battista Hospital - Torino - Italy
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Pr. Mihai VOICULESCU, M.D.
Organizational Affiliation
National Coordinator - Center of Internal Medicine, Fundeni Clinical Institute - Bucharest - Romania
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Pr. Manuel ROMERO-GOMEZ, M.D.
Organizational Affiliation
National Coordinator - Valme University hospital - Sevilla - Spain
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Pr. Quentin M. ANSTEE, M.D.
Organizational Affiliation
National Coordinator - Freeman Hospital - Newcastle - UK
Official's Role
Principal Investigator
Facility Information:
Facility Name
Site 920
City
Fresno
State/Province
California
ZIP/Postal Code
CA 9372
Country
United States
Facility Name
Site 903
City
La Jolla
State/Province
California
ZIP/Postal Code
CA 92037
Country
United States
Facility Name
Site 911
City
Aurora
State/Province
Colorado
ZIP/Postal Code
CO 80045
Country
United States
Facility Name
Site 912
City
Gainesville
State/Province
Florida
ZIP/Postal Code
FL 32610-0277
Country
United States
Facility Name
Site 924
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
GA 30303
Country
United States
Facility Name
Site 917
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
GA 30322
Country
United States
Facility Name
Site 909
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
LA 70112-2600
Country
United States
Facility Name
Site 921
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
MA 01655
Country
United States
Facility Name
Site 902
City
Detroit
State/Province
Michigan
ZIP/Postal Code
MI 48202
Country
United States
Facility Name
Site 927
City
New York
State/Province
New York
ZIP/Postal Code
NY 10029-6574
Country
United States
Facility Name
Site 908
City
Durham
State/Province
North Carolina
ZIP/Postal Code
NC 27710
Country
United States
Facility Name
Site 919
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
PA 19104
Country
United States
Facility Name
Site 916
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
TN 38104
Country
United States
Facility Name
Site 913
City
Fort Sam Houston
State/Province
Texas
ZIP/Postal Code
TX 78234
Country
United States
Facility Name
Site 923
City
Houston
State/Province
Texas
ZIP/Postal Code
TX 77030
Country
United States
Facility Name
Site 906
City
San Antonio
State/Province
Texas
ZIP/Postal Code
TX 78215
Country
United States
Facility Name
Site 931
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
UT 84132
Country
United States
Facility Name
Site 930
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
VA 22908
Country
United States
Facility Name
Site 901
City
Richmond
State/Province
Virginia
ZIP/Postal Code
VA 23298
Country
United States
Facility Name
Site 205
City
Brussels
ZIP/Postal Code
1070
Country
Belgium
Facility Name
Site 201
City
Edegem
ZIP/Postal Code
B-2650
Country
Belgium
Facility Name
Site 204
City
Gent
ZIP/Postal Code
B-9000
Country
Belgium
Facility Name
Site 202
City
Haine-Saint-Paul
ZIP/Postal Code
7100
Country
Belgium
Facility Name
Site 203
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Site 106
City
Amiens
ZIP/Postal Code
80054
Country
France
Facility Name
Site 102
City
Angers
ZIP/Postal Code
49933
Country
France
Facility Name
Site 114
City
Clichy
ZIP/Postal Code
92110
Country
France
Facility Name
Site 103
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
Site 113
City
Lyon
ZIP/Postal Code
69317
Country
France
Facility Name
Site 111
City
Marseille
ZIP/Postal Code
13285
Country
France
Facility Name
Site 108
City
Montpellier
ZIP/Postal Code
34295
Country
France
Facility Name
Site 104
City
Nantes
ZIP/Postal Code
44093
Country
France
Facility Name
Site 109
City
Nice
ZIP/Postal Code
06202
Country
France
Facility Name
Site 112
City
Paris
ZIP/Postal Code
75571
Country
France
Facility Name
Site 101
City
Paris
ZIP/Postal Code
75651
Country
France
Facility Name
Site 107
City
Pessac
ZIP/Postal Code
33604
Country
France
Facility Name
Site 405
City
Bonn
ZIP/Postal Code
53127
Country
Germany
Facility Name
Site 404
City
Mainz
ZIP/Postal Code
55131
Country
Germany
Facility Name
Site 507
City
Milano
ZIP/Postal Code
20122
Country
Italy
Facility Name
Site 503
City
Palermo
ZIP/Postal Code
90127
Country
Italy
Facility Name
Site 504
City
Roma
ZIP/Postal Code
00133
Country
Italy
Facility Name
Site 501
City
Torino
ZIP/Postal Code
10126
Country
Italy
Facility Name
Site 303
City
Amsterdam
ZIP/Postal Code
1100
Country
Netherlands
Facility Name
Site 302
City
Nijmegen
ZIP/Postal Code
6500
Country
Netherlands
Facility Name
Site 603
City
Bucharest
ZIP/Postal Code
021105
Country
Romania
Facility Name
Site 601
City
Bucharest
ZIP/Postal Code
022328
Country
Romania
Facility Name
Site 602
City
Bucharest
ZIP/Postal Code
022328
Country
Romania
Facility Name
Site 703
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Site 707
City
Majadahonda
ZIP/Postal Code
28222
Country
Spain
Facility Name
Site 705
City
Malaga
ZIP/Postal Code
29010
Country
Spain
Facility Name
Site 706
City
Santander
ZIP/Postal Code
39008
Country
Spain
Facility Name
Site 701
City
Sevilla
ZIP/Postal Code
41014
Country
Spain
Facility Name
Site 802
City
Camberley
ZIP/Postal Code
GU16 7UJ
Country
United Kingdom
Facility Name
Site 808
City
Hull
ZIP/Postal Code
HU3 2JZ
Country
United Kingdom
Facility Name
Site 801
City
Newcastle Upon Tyne
ZIP/Postal Code
NE7 7DN
Country
United Kingdom
Facility Name
Site 803
City
Nottingham
ZIP/Postal Code
NG7 2UH
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
26874076
Citation
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. Erratum In: Gastroenterology. 2017 Jun;152(8):2084.
Results Reference
derived
Learn more about this trial
Phase IIb Study to Evaluate the Efficacy and Safety of GFT505 Versus Placebo in Patients With Non-Alcoholic Steatohepatitis (NASH)
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