NATIVE: Phase 2b Study in NASH to Assess IVA337

• Sponsor: Inventiva Pharma (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03008070
• Collaborator: (none)
• Enrollment: 247
• Locations: 85
• Arms: 3
• Actual Duration (Months): 37.2
• Patients Per Site: 2.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Non-alcoholic steatohepatitis, abbreviated as NASH, is a chronic liver disease that may progress to cirrhosis. The disease is mostly associated with obesity and type 2 diabetes mellitus, or insulin resistance and is very common. However, Treatment of NASH is a significant unmet clinical need.

IVA337 (lanifibranor) is a next generation pan-PPAR (peroxisome proliferator-activated receptors) agonist addressing the pathophysiology of NASH : metabolic, inflammatory and fibrotic.

The purpose of this research is to evaluate the efficacy and the safety of two doses of IVA337 (800mg, 1200 mg) per day for 24 weeks versus placebo in adult NASH patients with liver steatosis and moderate to severe necroinflammation without cirrhosis.

Condition or Disease	Intervention/Treatment	Phase
Non-Alcoholic Steatohepatitis (NASH)	Drug: IVA337; Drug: IVA337; Drug: Placebo	Phase 2

Detailed Description

Randomized (stratified on diabetes), placebo-controlled, double-blind, parallel-assignment, dose-range multicenter study

There are 3 parallel treatment groups: placebo, IVA337 800mg once a day (Quaque Die, QD) and IVA337 1200mg QD (identical tablets of 400mg IVA337 or placebo). Both, patient and investigator are blinded.

For each patient, the study duration will be an overall of 6 to 8 months (with a 10-day to 4-week selection period, a 24-week treatment period and a 4-week follow-up period).

Study Design

• Study Type: Interventional
• Actual Enrollment: 247 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-controlled, Multicenter, Dose-range, Proof-of-concept, 24-week Treatment Study of IVA337 in Adult Subjects With Nonalcoholic Steatohepatitis (NASH)
• Actual Study Start Date: Feb 7, 2017
• Actual Primary Completion Date: Feb 20, 2020
• Actual Study Completion Date: Mar 16, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IVA337 1200mg IVA337 400mg, once a day (Quaque Die, QD) with food	Drug: IVA337; 1200mg
Experimental: IVA337 800mg IVA337 400mg, once a day (Quaque Die, QD) with food	Drug: IVA337; 800mg
Placebo Comparator: Placebo Placebo to match, once a day (Quaque Die, QD) with food	Drug: Placebo; Placebo to match

Outcome Measures

Primary Outcome Measures

1. SAF Activity Score (SAF-A) Decrease of at Least 2 Points With no Worsening of the CRN Fibrosis Score (CRN-F) [24 weeks]

   SAF-A is the activity part of the Steatosis Activity Fibrosis [SAF] histological score, calculated as the sum of lobular inflamation score and balloning score. No worsening of fibrosis means that the CRN fibrosis score (CRN-F) remains stable or decreases.

Secondary Outcome Measures

1. NASH Improvement [24 weeks]

   NASH improvement is defined as a decrease of at least 2 points in NAS score (sum of CRN Steatosis, Inflammation and Ballooning scores) without worsening of CRN Fibrosis score.

2. NASH Resolution and no Worsening of Fibrosis [24 weeks]

   Resolution of NASH is defined as a CRN Inflammation score equal to 0 or 1, and a CRN Ballooning score equal to 0. No worsening of fibrosis means that the CRN fibrosis score remains stable or decreases.

3. Improvement of Fibrosis by at Least 1 Stage and no Worsening of NASH [24 weeks]

   Improvement of fibrosis is defined as a decrease of at least one stage in CRN Fibrosis score. No worsening of NASH is defined as no increase of CRN Steatosis score, no increase of CRN Inflammation score ans no increase of CRN Ballooning score.

4. Activity (SAF-A) Improvement [24 weeks]

   SAF-A is the activity part of the Steatosis Activity Fibrosis [SAF] histological score, calculated as the sum of lobular inflamation score and balloning score. Improvement of SAF-A is defined as a decrease of at least 1 point.

5. Steatosis (CRN-S) Improvement [24 weeks]

   Improvement of CRN Steatosis score (CRN-S) is defined as a decrease of at least 1 point.

6. Lobular Inflammation (CRN-I) Improvement [24 weeks]

   Improvement of CRN Lobular inflammation score (CRN-I) is defined as a decrease of at least 1 point.

7. Hepatocyte Balooning (CRN-B) Improvement [24 weeks]

   Improvement of CRN Ballooning (CRN-B) is defined as a decrease of at least 1 point.

8. Fibrosis (CRN-F) Improvement [24 weeks]

   Improvement of CRN Fibrosis score (CRN-F) is defined as a decrease of at least 1 point.

9. Modified ISHAK Fibrosis (ISHAK-F) Improvement [24 weeks]

   Improvement of Modified ISHAK Fibrosis (ISHAK-F) is defined as a decrease of at least 1 point.

10. Absolute Change in ALT [24 weeks]

    Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start.

11. Absolute Change in AST [24 weeks]

    Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start.

12. Absolute Change in GGT [24 weeks]

    Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start.

13. Absolute Change in Fibrinogen [24 weeks]

    Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start.

14. Absolute Change in Hs-CRP [24 weeks]

    Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start.

15. Absolute Change in Alpha2 Macroglobulin [24 weeks]

    Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start.

16. Absolute Change in Haptoglobulin [24 weeks]

    Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start.

17. Absolute Change of Fasting Plasma Glucose [24 weeks]

    Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start. Only fasting values were considered.

18. Absolute Change in Insulin [24 weeks]

    Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start. Only fasting values were considered.

19. Absolute Change in HOMA Index [24 weeks]

    Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start. Only fasting values were considered.

20. Absolute Change in HbA1c [24 weeks]

    Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start. Only fasting values were considered.

21. Absolute Change in Total Cholesterol [24 weeks]

    Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start. Only fasting values were considered.

22. Absolute Change of HDL-Cholesterol [24 weeks]

    Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start. Only fasting values were considered.

23. Absolute Change of LDL-Cholesterol [24 weeks]

    Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start. Only fasting values were considered.

24. Absolute Change in Triglycerides [24 weeks]

    Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start. Only fasting values were considered.

25. Absolute Change in Apo A1 [24 weeks]

    Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start. Only fasting values were considered.

26. Absolute Change in Adiponectin [24 weeks]

    Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start. Only fasting values were considered.

27. Resolution of NASH and Improvement of Fibrosis by at Least 1 Stage [From baseline to Week 24.]

    Resolution of NASH is defined as a CRN Inflammation score equel to 0 or 1, and a CRN ballooning score equal to 0. Improvement of firbosis is defined as a decrease of at least one stage in CRN Fibrosis score.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Adult subjects, age ≥18 years.

• NASH histological diagnosis according to the currently accepted definition of both EASL and AASLD, requiring the combined presence of steatosis (any degree ≥ 5%) + lobular inflammation of any degree + liver cell ballooning of any amount, on a liver biopsy performed ≤ 6 months before screening in the study or at screening and confirmed by central reading during the screening period and

• SAF Activity score of 3 or 4 (>2)

• SAF Steatosis score ≥ 1

• SAF Fibrosis score < 4

• Subject agrees to have a liver biopsy performed after 24 weeks of treatment.

• Compensated liver disease

• No other causes of chronic liver disease (autoimmune, primary biliary cholangitis, Hepatitis B virus (HBV), hepatitis C virus (HCV), Wilson's, α-1-antitrypsin deficiency, hemochromatosis, etc…).

• If applicable, have a stable type 2 diabetes, defined as HbA1c ≤ 8.5% and fasting glycemia <10 mmol/L, no changes in medication in the previous 6 months, and no new symptoms associated with decompensated diabetes in the previous 3 months.

• Have a stable weight since the liver biopsy was performed defined by no more than a 5 % loss of initial body weight.

• Negative pregnancy test or post-menopausal. Women with childbearing potential (i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile) must be using a highly effective method of contraception (i.e. combined (estrogen and progestogen containing) hormonal/ progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomised partner). The contraceptive method will have to be followed for at least one menstruation cycle after the end of the study

• Subjects having given her/his written informed consent.

Exclusion Criteria:

• Evidence of another form of liver disease.

• History of sustained excess alcohol ingestion: daily alcohol consumption > 30 g/day (3 drinks per day) for males and > 20 g/day (2 drinks per day) for females.

• Unstable metabolic condition: Weight change > 5kg in the last three months, diabetes with poor glycemic control (HbA1c > 8.5%), introduction of an antidiabetic or of an anti-obesity drug/malabsorptive or restrictive bariatric (weight loss) surgery in the past 6 months prior to screening.

• History of gastrointestinal malabsorptive bariatric surgery within less than 5 years or ingestion of drugs known to produce hepatic steatosis including corticosteroids, high-dose estrogens, methotrexate, tetracycline or amiodarone in the previous 6 months.

• Significant systemic or major illnesses other than liver disease, including congestive heart failure (class C and D of the American Heart Association , AHA), unstable coronary artery disease, cerebrovascular disease, pulmonary disease, renal failure, organ transplantation, serious psychiatric disease, malignancy that, in the opinion of the investigator, would preclude treatment with IVA337 and/or adequate follow up.

• HB antigen >0, HCV Polymerase chain reaction (PCR) tests >0 (patients with a history of HCV infection can be included if HCV PCR is negative since more than 3 years), HIV infection.

• Pregnancy/lactation or inability to adhere to adequate contraception in women of child-bearing potential.

• Active malignancy except cutaneous basocellular carcinoma.

• Any other condition which, in the opinion of the investigator would impede competence or compliance or possibly hinder completion of the study.

• Body mass index (BMI) >45 kg/m2.

• Type 1 diabetes and type 2 diabetic patient on insulin.

• Diabetic ketoacidosis

• Fasting Triglycerides > 300 mg/dL.

• Hemostasis disorders or current treatment with anticoagulants.

• Contra-indication to liver biopsy.

• History of, or current cardiac dysrhythmias and/or a history of cardiovascular disease event, including myocardial infarction, except patients with only well controlled hypertension. Any clinically significant ECG abnormality reported by central ECG reading.

• Participation in any other clinical study within the previous 3 months.

• Have a known hypersensitivity to any of the ingredients or excipients of the Investigational medicinal product (IMP)

• Be possibly dependent on the Investigator or the sponsor (e.g., including, but not limited to, affiliated employee).

• Creatine phosphokinase (CPK)>5 x ULN

• Osteopenia or any other well documented Bone disease. Patient without well documented osteopenia treated with vitamin D and/or Calcium based supplements for preventive reasons can be included.

(The criteria below are applicable only for patients who will undergo a MRI/LMS in selected centers)

• Claustrophobia to a degree that prevents tolerance of MRI scanning procedure. Sedation is permitted at discretion of investigator.

• Metallic implant of any sort that prevents MRI examination including, but not limited to: aneurysm clips, metallic foreign body, vascular grafts or cardiac implants, neural stimulator, metallic contraceptive device, tattoo, body piercing that cannot be removed, cochlear implant; or any other contraindication to MRI examination.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	North Alabama GI Research Center	Madison	Alabama	United States	35758
2	ACTRI	La Jolla	California	United States	92037
3	National Research Institute	Los Angeles	California	United States	90057
4	Palmetto Research, LLC	Hialeah	Florida	United States	33016
5	Florida Digestive Health Specialists, LLP	Lakewood Ranch	Florida	United States	34211
6	Northeast GI Research Division	Concord	Massachusetts	United States	29027
7	Duke University Medical Center	Durham	North Carolina	United States	27710
8	Carolina's Center for Liver Disease/CHG	Huntersville	North Carolina	United States	28078
9	Jefferson University hospital	Philadelphia	Pennsylvania	United States	19107
10	Digestive Health Research, LLC	Hermitage	Tennessee	United States	37076
11	The Texas Liver Institute	San Antonio	Texas	United States	78215
12	Digestive Health Research, LLC	San Antonio	Texas	United States	78229
13	University of Virginia Health System	Charlottesville	Virginia	United States	22908
14	Virginia Commonwealth University	Richmond	Virginia	United States	23298
15	Flinders Medical Centre Department of Hepatology	Bedford Park		Australia	SA 5042
16	Monash Medical Centre	Clayton		Australia	3168
17	Lyell McEwin Hospital & The University of Adelaide	Elizabeth Vale		Australia	SA 5112
18	Royal Brisbane and Women's Hospital	Herston		Australia
19	Fiona Stanley Hospital	Murdoch		Australia	WA 6150
20	Medical University Vienna	Vienna		Austria	1090
21	Hopital Erasme	Brussels		Belgium	1070
22	Clinique Universitaire Saint-luc	Brussels		Belgium	1200
23	Antwerp University Hospital	Edegem		Belgium	2650
24	Ziekenhuis Oost Limburg	Genk		Belgium
25	UZ Gent	Gent		Belgium
26	"DCC Alexandrovska", EOOD	Sofia		Bulgaria
27	Acibadem City Clinic Tokuda Hospital	Sofia		Bulgaria
28	Acibadem City Clinic University Hospital EOOD	Sofia		Bulgaria
29	MHAT "Sveta Anna" Sofia	Sofia		Bulgaria
30	Military Medical Academy - MHAT	Sofia		Bulgaria
31	UMHAT "Sv. Ivan Rilski"	Sofia		Bulgaria
32	UMHAT "Tsaritsa Yoanna-ISUL"	Sofia		Bulgaria
33	University of Calgary	Calgary		Canada
34	The Bailey Health Clinic	Edmonton		Canada
35	CISSS de la Montérégie Centre	Greenfield Park		Canada
36	University of Western Ontario, London Health Sciences Centre	London		Canada
37	McGill University Health Centre (MUHC)	Montréal		Canada
38	Medpharmgene, Inc	Montréal		Canada
39	LAIR Centre	Vancouver		Canada
40	Researchsite S.R.O.	Plzen		Czechia	30100
41	Klin Med S.R.O.	Praha		Czechia	1200
42	Institut klinické a experimentální medicíny, IKEM	Praha		Czechia	14021
43	CHU Angers	Angers		France	49933
44	CHRU Besançon	Besancon		France	25000
45	Centre Hospitalier de Bordeaux	Bordeaux		France
46	CHU Henri Mondor	Créteil		France
47	CHU de Grenoble	Grenoble		France
48	Hôpital de La Croix Rousse	Lyon		France
49	Centre Hospitalier Régional Universitaire de Montpellier	Montpellier		France
50	CHU de Nice	Nice		France	06202
51	Hôpital Saint Antoine	Paris		France	75012
52	Hôpital La Pitié Salpétrière	Paris		France	75013
53	Hôpital Beaujon	Paris		France
54	Centre Hospitalier Universitaire de Rennes	Rennes		France
55	Hôpital de Hautepierre	Strasbourg		France
56	Hôpital Purpan - Centre Hospitalier Universitaire (CHU) de Toulouse	Toulouse		France
57	RWTH University Hospital	Aachen		Germany	52074
58	Innere Medizin II - Universitätsklinik Freiburg	Freiburg		Germany
59	Medizinischen Klinik IV	Heidelberg		Germany	69120
60	Universitätsmedizin Mainz, I. Med. Klinik	Mainz		Germany	55131
61	Universitätsklinikum Münster	Münster		Germany
62	University Hospital Würzburg	Wurzburg		Germany	97080
63	Ospedali Riuniti di Ancona-Università Politecnica delle Marche	Ancona		Italy	60126
64	Granda Ospedale Maggiore Policlinico - Università di Milano	Milano		Italy	20122
65	Pol. Giaccone	Palermo		Italy	90127
66	Fondazione Policlinico Agostino Gemelli	Roma		Italy	00168
67	Poliambulatorio Giovanni Paolo II	San Giovanni Rotondo		Italy
68	A.O. Città della Salute e della Scienza di Torino	Torino		Italy	10126
69	CAP Research	Quatre Bornes		Mauritius
70	Oddzial Gastroenterologii Hepatologii UCK	Katowice		Poland
71	Katedra i Klinika Chorób Zakaźnych i Hepatologii Uniwersytetu Medycznego w Łodzi	Lodz		Poland	91-347
72	Klinika Chorób Zakaźnych	Lublin		Poland	20-081
73	Centrum Badan Klinicznych	Wrocław		Poland
74	General hospital Celje	Celje		Slovenia
75	General Hospital Murska Sobota	Murska Sobota		Slovenia
76	Vall d'Hebron Hospital	Barcelona		Spain
77	Hospital Puerta de Hierro MAJADAHONDA	Madrid		Spain	28222
78	Virgen de la Victoria University Hospital	Malaga		Spain	29010
79	Hospital Universitario Marqués de Valdecilla	Santander		Spain	39008
80	Hospital Virgen del Rocío	Sevilla		Spain	41013
81	Universitätsklinik für Viszerale Chirurgie und Medizin	Bern		Switzerland
82	Epatocentro Ticino	Lugano		Switzerland	6900
83	Kings College Hospital NHS Foundation Trust	London		United Kingdom
84	Freeman Hospital, Newcastle University	Newcastle		United Kingdom	NE7 7DN
85	Nottingham University Hospitals NHS Trust	Nottingham		United Kingdom

Sponsors and Collaborators

• Inventiva Pharma

Investigators

• Principal Investigator: Sven FRANCQUE, MD, PhD, Division of Gastroenterology and Hepatology, Antwerp University Hospital, Wilrijkstraat 10, B-2650 Edegem, Belgium

Study Documents (Full-Text)

• Statistical Analysis Plan - May 13, 2020
• Study Protocol - Mar 25, 2020

More Information

Publications

None provided.

• Responsible Party: Inventiva Pharma
• ClinicalTrials.gov Identifier: NCT03008070
• Other Study ID Numbers: IVA_01_337_HNAS_16_002; 2016-001979-70
• First Posted: Jan 2, 2017
• Last Update Posted: Apr 12, 2021
• Last Verified: Mar 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Inventiva Pharma: Non-Alcoholic Steatohepatitis; NASH; peroxisome proliferator-activated receptor (PPAR); Liver Diseases; Fibrosis; Fatty Liver; Non-alcoholic Fatty Liver Disease; Digestive System Diseases; IVA337
• Additional relevant MeSH terms: Fatty Liver; Non-alcoholic Fatty Liver Disease

Study Results

Participant Flow

Recruitment Details	Recruitment of patients started in February 2017, and last patient was recruited on March 2019. A total of 868 patients were screened for the study.
Pre-assignment Detail	Patients were invited to participate into the study by their referent doctor according to the patient's medical records. Patients had to fulfil all the inclusion and none of the exclusion criteria to be eligible. A total of 247 patients were randomised, and 621 were not randomised.Main reason for non randomization was inclusion/exclusion criteria not met (470 - 76%).

Arm/Group Title	Lanifibranor 1200mg	Lanifibranor 800mg	Placebo
Arm/Group Description	Lanifibranor 400mg, once a day (Quaque Die, QD) with food Lanifibranor: 1200mg	Lanifibranor 400mg, once a day (Quaque Die, QD) with food Lanifibranor: 800mg	Placebo to match, once a day (Quaque Die, QD) with food Placebo: Placebo to match
Period Title: Overall Study
STARTED	83	83	81
COMPLETED	77	77	74
NOT COMPLETED	6	6	7

Baseline Characteristics

Arm/Group Title	IVA337 1200mg	IVA337 800mg	Placebo	Total
Arm/Group Description	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 1200mg	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 800mg	Placebo to match, once a day (Quaque Die, QD) with food Placebo: Placebo to match	Total of all reporting groups
Overall Participants	83	83	81	247
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	67 80.7%	69 83.1%	63 77.8%	199 80.6%
>=65 years	16 19.3%	14 16.9%	18 22.2%	48 19.4%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52.2 (13.8)	55 (10.4)	53.4 (13.1)	53.6 (12.5)
Sex: Female, Male (Count of Participants)
Female	49 59%	54 65.1%	41 50.6%	144 58.3%
Male	34 41%	29 34.9%	40 49.4%	103 41.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	2 2.5%	2 0.8%
Asian	2 2.4%	1 1.2%	2 2.5%	5 2%
Native Hawaiian or Other Pacific Islander	0 0%	1 1.2%	0 0%	1 0.4%
Black or African American	3 3.6%	1 1.2%	3 3.7%	7 2.8%
White	78 94%	80 96.4%	74 91.4%	232 93.9%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	13 15.7%	11 13.3%	12 14.8%	36 14.6%
Czechia	3 3.6%	2 2.4%	3 3.7%	8 3.2%
United Kingdom	3 3.6%	2 2.4%	2 2.5%	7 2.8%
Mauritius	2 2.4%	3 3.6%	2 2.5%	7 2.8%
Switzerland	0 0%	3 3.6%	1 1.2%	4 1.6%
Spain	3 3.6%	4 4.8%	5 6.2%	12 4.9%
Canada	3 3.6%	1 1.2%	4 4.9%	8 3.2%
Austria	0 0%	1 1.2%	0 0%	1 0.4%
Belgium	10 12%	11 13.3%	11 13.6%	32 13%
Poland	1 1.2%	2 2.4%	3 3.7%	6 2.4%
Italy	3 3.6%	1 1.2%	1 1.2%	5 2%
Slovenia	0 0%	1 1.2%	0 0%	1 0.4%
Australia	3 3.6%	7 8.4%	3 3.7%	13 5.3%
Bulgaria	17 20.5%	16 19.3%	22 27.2%	55 22.3%
France	15 18.1%	15 18.1%	9 11.1%	39 15.8%
Germany	7 8.4%	3 3.6%	3 3.7%	13 5.3%

Outcome Measures

1. Primary Outcome

Title	SAF Activity Score (SAF-A) Decrease of at Least 2 Points With no Worsening of the CRN Fibrosis Score (CRN-F)
Description	SAF-A is the activity part of the Steatosis Activity Fibrosis [SAF] histological score, calculated as the sum of lobular inflamation score and balloning score. No worsening of fibrosis means that the CRN fibrosis score (CRN-F) remains stable or decreases.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IVA337 1200mg	IVA337 800mg	Placebo
Arm/Group Description	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 1200mg	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 800mg	Placebo to match, once a day (Quaque Die, QD) with food Placebo: Placebo to match
Measure Participants	83	83	81
Yes	41 49.4%	34 41%	22 27.2%
No	42 50.6%	49 59%	59 72.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IVA337 800mg, Placebo
	Comments	The primary endpoint was a binary outcome (Yes/No). Responders rates were compared between the placebo and lanifibranor 800 mg at the end of the treatment period (week 24) using a Cochran Mantel Haenzel test stratified on diabetic status at baseline (that was the stratified factors in the randomisation). The CMH risk ratio is used to estimate the effect size. Patients with missing data are considered as non-responders.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	=0.061
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.52
	Confidence Interval	(2-Sided) 95%; 0.98 to 2.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	IVA337 1200mg, Placebo
	Comments	The primary endpoint was a binary outcome (Yes/No). Responders rates were compared between the placebo and lanifibranor 1200 mg at the end of the treatment period (week 24) using a Cochran Mantel Haenzel test stratified on diabetic status at baseline (that was the stratified factors in the randomisation). The CMH risk ratio is used to estimate the effect size. Patients with missing data are considered as non-responders.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	=0.004
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.82
	Confidence Interval	(2-Sided) 95%; 1.24 to 2.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	NASH Improvement
Description	NASH improvement is defined as a decrease of at least 2 points in NAS score (sum of CRN Steatosis, Inflammation and Ballooning scores) without worsening of CRN Fibrosis score.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IVA337 1200mg	IVA337 800mg	Placebo
Arm/Group Description	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 1200mg	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 800mg	Placebo to match, once a day (Quaque Die, QD) with food Placebo: Placebo to match
Measure Participants	83	83	81
Yes	53 63.9%	43 51.8%	26 32.1%
No	30 36.1%	40 48.2%	55 67.9%

3. Secondary Outcome

Title	NASH Resolution and no Worsening of Fibrosis
Description	Resolution of NASH is defined as a CRN Inflammation score equal to 0 or 1, and a CRN Ballooning score equal to 0. No worsening of fibrosis means that the CRN fibrosis score remains stable or decreases.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IVA337 1200mg	IVA337 800mg	Placebo
Arm/Group Description	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 1200mg	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 800mg	Placebo to match, once a day (Quaque Die, QD) with food Placebo: Placebo to match
Measure Participants	83	83	81
Yes	37 44.6%	27 32.5%	15 18.5%
No	46 55.4%	56 67.5%	66 81.5%

4. Secondary Outcome

Title	Improvement of Fibrosis by at Least 1 Stage and no Worsening of NASH
Description	Improvement of fibrosis is defined as a decrease of at least one stage in CRN Fibrosis score. No worsening of NASH is defined as no increase of CRN Steatosis score, no increase of CRN Inflammation score ans no increase of CRN Ballooning score.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IVA337 1200mg	IVA337 800mg	Placebo
Arm/Group Description	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 1200mg	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 800mg	Placebo to match, once a day (Quaque Die, QD) with food Placebo: Placebo to match
Measure Participants	83	83	81
Yes	35 42.2%	23 27.7%	19 23.5%
No	48 57.8%	60 72.3%	62 76.5%

5. Secondary Outcome

Title	Activity (SAF-A) Improvement
Description	SAF-A is the activity part of the Steatosis Activity Fibrosis [SAF] histological score, calculated as the sum of lobular inflamation score and balloning score. Improvement of SAF-A is defined as a decrease of at least 1 point.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IVA337 1200mg	IVA337 800mg	Placebo
Arm/Group Description	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 1200mg	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 800mg	Placebo to match, once a day (Quaque Die, QD) with food Placebo: Placebo to match
Measure Participants	83	83	81
Yes	62 74.7%	54 65.1%	40 49.4%
No	21 25.3%	29 34.9%	41 50.6%

6. Secondary Outcome

Title	Steatosis (CRN-S) Improvement
Description	Improvement of CRN Steatosis score (CRN-S) is defined as a decrease of at least 1 point.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IVA337 1200mg	IVA337 800mg	Placebo
Arm/Group Description	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 1200mg	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 800mg	Placebo to match, once a day (Quaque Die, QD) with food Placebo: Placebo to match
Measure Participants	83	83	81
Yes	54 65.1%	46 55.4%	21 25.9%
No	29 34.9%	37 44.6%	60 74.1%

7. Secondary Outcome

Title	Lobular Inflammation (CRN-I) Improvement
Description	Improvement of CRN Lobular inflammation score (CRN-I) is defined as a decrease of at least 1 point.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IVA337 1200mg	IVA337 800mg	Placebo
Arm/Group Description	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 1200mg	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 800mg	Placebo to match, once a day (Quaque Die, QD) with food Placebo: Placebo to match
Measure Participants	83	83	81
Yes	43 51.8%	34 41%	30 37%
No	40 48.2%	49 59%	51 63%

8. Secondary Outcome

Title	Hepatocyte Balooning (CRN-B) Improvement
Description	Improvement of CRN Ballooning (CRN-B) is defined as a decrease of at least 1 point.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IVA337 1200mg	IVA337 800mg	Placebo
Arm/Group Description	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 1200mg	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 800mg	Placebo to match, once a day (Quaque Die, QD) with food Placebo: Placebo to match
Measure Participants	83	83	81
Yes	60 72.3%	54 65.1%	37 45.7%
No	23 27.7%	29 34.9%	44 54.3%

9. Secondary Outcome

Title	Fibrosis (CRN-F) Improvement
Description	Improvement of CRN Fibrosis score (CRN-F) is defined as a decrease of at least 1 point.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IVA337 1200mg	IVA337 800mg	Placebo
Arm/Group Description	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 1200mg	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 800mg	Placebo to match, once a day (Quaque Die, QD) with food Placebo: Placebo to match
Measure Participants	83	83	81
Yes	36 43.4%	28 33.7%	22 27.2%
No	47 56.6%	55 66.3%	59 72.8%

10. Secondary Outcome

Title	Modified ISHAK Fibrosis (ISHAK-F) Improvement
Description	Improvement of Modified ISHAK Fibrosis (ISHAK-F) is defined as a decrease of at least 1 point.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IVA337 1200mg	IVA337 800mg	Placebo
Arm/Group Description	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 1200mg	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 800mg	Placebo to match, once a day (Quaque Die, QD) with food Placebo: Placebo to match
Measure Participants	83	83	81
Yes	41 49.4%	32 38.6%	25 30.9%
No	42 50.6%	51 61.4%	56 69.1%

11. Secondary Outcome

Title	Absolute Change in ALT
Description	Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IVA337 1200mg	IVA337 800mg	Placebo
Arm/Group Description	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 1200mg	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 800mg	Placebo to match, once a day (Quaque Die, QD) with food Placebo: Placebo to match
Measure Participants	74	72	72
Mean (Standard Error) [U/L]	-24.54 (3.82)	-26.08 (3.85)	-1.4 (3.88)

12. Secondary Outcome

Title	Absolute Change in AST
Description	Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IVA337 1200mg	IVA337 800mg	Placebo
Arm/Group Description	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 1200mg	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 800mg	Placebo to match, once a day (Quaque Die, QD) with food Placebo: Placebo to match
Measure Participants	74	72	72
Mean (Standard Error) [U/L]	-12.04 (3.17)	-15.11 (3.2)	-0.08 (3.22)

13. Secondary Outcome

Title	Absolute Change in GGT
Description	Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IVA337 1200mg	IVA337 800mg	Placebo
Arm/Group Description	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 1200mg	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 800mg	Placebo to match, once a day (Quaque Die, QD) with food Placebo: Placebo to match
Measure Participants	74	72	73
Mean (Standard Error) [U/L]	-27.87 (5.57)	-43.38 (5.61)	4.41 (5.65)

14. Secondary Outcome

Title	Absolute Change in Fibrinogen
Description	Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IVA337 1200mg	IVA337 800mg	Placebo
Arm/Group Description	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 1200mg	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 800mg	Placebo to match, once a day (Quaque Die, QD) with food Placebo: Placebo to match
Measure Participants	73	69	73
Mean (Standard Error) [g/L]	-0.14 (0.81)	-0.10 (0.61)	0.02 (0.67)

15. Secondary Outcome

Title	Absolute Change in Hs-CRP
Description	Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IVA337 1200mg	IVA337 800mg	Placebo
Arm/Group Description	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 1200mg	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 800mg	Placebo to match, once a day (Quaque Die, QD) with food Placebo: Placebo to match
Measure Participants	74	72	72
Mean (Standard Error) [mg/L]	-1.37 (0.46)	-2.05 (0.47)	0.11 (0.47)

16. Secondary Outcome

Title	Absolute Change in Alpha2 Macroglobulin
Description	Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IVA337 1200mg	IVA337 800mg	Placebo
Arm/Group Description	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 1200mg	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 800mg	Placebo to match, once a day (Quaque Die, QD) with food Placebo: Placebo to match
Measure Participants	72	68	71
Mean (Standard Error) [g/L]	0.13 (0.38)	0.15 (0.40)	0.05 (0.35)

17. Secondary Outcome

Title	Absolute Change in Haptoglobulin
Description	Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IVA337 1200mg	IVA337 800mg	Placebo
Arm/Group Description	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 1200mg	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 800mg	Placebo to match, once a day (Quaque Die, QD) with food Placebo: Placebo to match
Measure Participants	74	72	72
Mean (Standard Error) [g/L]	-0.099 (0.378)	-0.053 (0.256)	0.074 (0.291)

18. Secondary Outcome

Title	Absolute Change of Fasting Plasma Glucose
Description	Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start. Only fasting values were considered.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IVA337 1200mg	IVA337 800mg	Placebo
Arm/Group Description	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 1200mg	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 800mg	Placebo to match, once a day (Quaque Die, QD) with food Placebo: Placebo to match
Measure Participants	73	71	72
Mean (Standard Error) [mmol/L]	-0.6 (0.12)	-0.78 (0.12)	0.24 (0.12)

19. Secondary Outcome

Title	Absolute Change in Insulin
Description	Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start. Only fasting values were considered.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IVA337 1200mg	IVA337 800mg	Placebo
Arm/Group Description	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 1200mg	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 800mg	Placebo to match, once a day (Quaque Die, QD) with food Placebo: Placebo to match
Measure Participants	65	68	66
Mean (Standard Error) [pmol/L]	-114.91 (11.75)	-118.66 (11.66)	-35.7 (11.6)

20. Secondary Outcome

Title	Absolute Change in HOMA Index
Description	Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start. Only fasting values were considered.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IVA337 1200mg	IVA337 800mg	Placebo
Arm/Group Description	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 1200mg	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 800mg	Placebo to match, once a day (Quaque Die, QD) with food Placebo: Placebo to match
Measure Participants	63	64	65
Mean (Standard Error) [index]	-5.46 (0.58)	-5.79 (0.58)	-1.47 (0.57)

21. Secondary Outcome

Title	Absolute Change in HbA1c
Description	Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start. Only fasting values were considered.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IVA337 1200mg	IVA337 800mg	Placebo
Arm/Group Description	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 1200mg	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 800mg	Placebo to match, once a day (Quaque Die, QD) with food Placebo: Placebo to match
Measure Participants	74	72	72
Mean (Standard Error) [percentage]	-0.41 (0.05)	-0.38 (0.05)	0.07 (0.05)

22. Secondary Outcome

Title	Absolute Change in Total Cholesterol
Description	Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start. Only fasting values were considered.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IVA337 1200mg	IVA337 800mg	Placebo
Arm/Group Description	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 1200mg	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 800mg	Placebo to match, once a day (Quaque Die, QD) with food Placebo: Placebo to match
Measure Participants	74	72	73
Mean (Standard Error) [mmol/L]	-0.07 (0.07)	-0.02 (0.08)	0.01 (0.08)

23. Secondary Outcome

Title	Absolute Change of HDL-Cholesterol
Description	Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start. Only fasting values were considered.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IVA337 1200mg	IVA337 800mg	Placebo
Arm/Group Description	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 1200mg	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 800mg	Placebo to match, once a day (Quaque Die, QD) with food Placebo: Placebo to match
Measure Participants	74	71	73
Mean (Standard Error) [mmol/L]	0.11 (0.02)	0.16 (0.02)	0.01 (0.02)

24. Secondary Outcome

Title	Absolute Change of LDL-Cholesterol
Description	Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start. Only fasting values were considered.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IVA337 1200mg	IVA337 800mg	Placebo
Arm/Group Description	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 1200mg	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 800mg	Placebo to match, once a day (Quaque Die, QD) with food Placebo: Placebo to match
Measure Participants	73	71	69
Mean (Standard Error) [mmol/L]	0.03 (0.07)	0.03 (0.07)	0.01 (0.07)

25. Secondary Outcome

Title	Absolute Change in Triglycerides
Description	Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start. Only fasting values were considered.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IVA337 1200mg	IVA337 800mg	Placebo
Arm/Group Description	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 1200mg	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 800mg	Placebo to match, once a day (Quaque Die, QD) with food Placebo: Placebo to match
Measure Participants	74	71	72
Mean (Standard Error) [mmol/L]	-0.44 (0.09)	-0.49 (0.09)	0.06 (0.09)

26. Secondary Outcome

Title	Absolute Change in Apo A1
Description	Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start. Only fasting values were considered.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IVA337 1200mg	IVA337 800mg	Placebo
Arm/Group Description	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 1200mg	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 800mg	Placebo to match, once a day (Quaque Die, QD) with food Placebo: Placebo to match
Measure Participants	73	72	72
Mean (Standard Error) [mg/dL]	-4.39 (2.16)	-0.29 (2.19)	0.03 (2.18)

27. Secondary Outcome

Title	Absolute Change in Adiponectin
Description	Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start. Only fasting values were considered.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IVA337 1200mg	IVA337 800mg	Placebo
Arm/Group Description	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 1200mg	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 800mg	Placebo to match, once a day (Quaque Die, QD) with food Placebo: Placebo to match
Measure Participants	73	66	72
Mean (Standard Error) [microgram/mL]	17.12 (1.44)	11.95 (1.51)	-0.35 (1.44)

28. Secondary Outcome

Title	Resolution of NASH and Improvement of Fibrosis by at Least 1 Stage
Description	Resolution of NASH is defined as a CRN Inflammation score equel to 0 or 1, and a CRN ballooning score equal to 0. Improvement of firbosis is defined as a decrease of at least one stage in CRN Fibrosis score.
Time Frame	From baseline to Week 24.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lanifibranor 1200mg	Lanifibranor 800mg	Placebo
Arm/Group Description	Lanifibranor 400mg, once a day (Quaque Die, QD) with food Lanifibranor: 1200mg	Lanifibranor 400mg, once a day (Quaque Die, QD) with food Lanifibranor: 800mg	Placebo to match, once a day (Quaque Die, QD) with food Placebo: Placebo to match
Measure Participants	83	83	81
Yes	26 31.3%	17 20.5%	6 7.4%
No	57 68.7%	66 79.5%	75 92.6%

Adverse Events

Time Frame	On or after the first dose of treatment up to 30 days post last dose.
Arm/Group Title	IVA337 1200mg		IVA337 800mg		Placebo
Arm/Group Description	IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 1200mg		IVA337 400mg, once a day (Quaque Die, QD) with food IVA337: 800mg		Placebo to match, once a day (Quaque Die, QD) with food Placebo: Placebo to match
All Cause Mortality
	IVA337 1200mg		IVA337 800mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/83 (0%)		0/83 (0%)		0/81 (0%)
Serious Adverse Events
	IVA337 1200mg		IVA337 800mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/83 (8.4%)		3/83 (3.6%)		3/81 (3.7%)
Cardiac disorders
Angina unstable	1/83 (1.2%)	1	0/83 (0%)	0	0/81 (0%)	0
Cardiac failure	0/83 (0%)	0	0/83 (0%)	0	1/81 (1.2%)	1
Gastrointestinal disorders
Pancreatitis	0/83 (0%)	0	1/83 (1.2%)	1	0/81 (0%)	0
Hepatobiliary disorders
Pneumobilia	1/83 (1.2%)	1	0/83 (0%)	0	0/81 (0%)	0
Infections and infestations
Gastroenteritis	1/83 (1.2%)	1	0/83 (0%)	0	0/81 (0%)	0
Pyelonephritis	1/83 (1.2%)	1	0/83 (0%)	0	0/81 (0%)	0
Injury, poisoning and procedural complications
Post procedural haematoma	2/83 (2.4%)	2	1/83 (1.2%)	1	1/81 (1.2%)	1
Post procedural haemorrhage	1/83 (1.2%)	1	0/83 (0%)	0	0/81 (0%)	0
Procedural pain	1/83 (1.2%)	1	0/83 (0%)	0	0/81 (0%)	0
Wrist fracture	0/83 (0%)	0	0/83 (0%)	0	1/81 (1.2%)	1
Musculoskeletal and connective tissue disorders
Undifferentiated connective tissue disease	0/83 (0%)	0	1/83 (1.2%)	1	0/81 (0%)	0
Skin and subcutaneous tissue disorders
Urticaria	0/83 (0%)	0	0/83 (0%)	0	1/81 (1.2%)	1
Surgical and medical procedures
Foot operation	1/83 (1.2%)	1	0/83 (0%)	0	0/81 (0%)	0
Other (Not Including Serious) Adverse Events
	IVA337 1200mg		IVA337 800mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	60/83 (72.3%)		48/83 (57.8%)		30/81 (37%)
Gastrointestinal disorders
Diarrhoea	10/83 (12%)	11	8/83 (9.6%)	8	1/81 (1.2%)	2
Nausea	7/83 (8.4%)	7	8/83 (9.6%)	8	3/81 (3.7%)	3
Constipation	5/83 (6%)	5	3/83 (3.6%)	3	6/81 (7.4%)	6
General disorders
Fatigue	11/83 (13.3%)	11	3/83 (3.6%)	3	8/81 (9.9%)	8
Oedema peripheral	7/83 (8.4%)	7	5/83 (6%)	5	2/81 (2.5%)	2
Infections and infestations
Viral upper respiratory tract infection	3/83 (3.6%)	5	3/83 (3.6%)	4	5/81 (6.2%)	5
Investigations
Weight increased	7/83 (8.4%)	7	8/83 (9.6%)	8	0/81 (0%)	0
Transaminases increased	3/83 (3.6%)	3	5/83 (6%)	5	1/81 (1.2%)	1
Nervous system disorders
Headache	7/83 (8.4%)	7	4/83 (4.8%)	6	4/81 (4.9%)	5
Dizziness	6/83 (7.2%)	6	2/83 (2.4%)	3	3/81 (3.7%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.