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CompletedNCT03008070NATIVEUpdated Jul 19, 2023Results posted

Phase 2b Study in NASH to Assess IVA337

A Phase 2 interventional study of IVA337 and IVA337 in Non-Alcoholic Steatohepatitis (NASH), sponsored by Inventiva Pharma. Completed at 85 sites in 16 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-07-19.

Sponsored by Inventiva Pharma · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
247
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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).

02

Conditions studied

  • Non-Alcoholic Steatohepatitis (NASH)

Keywords

  • Non-Alcoholic Steatohepatitis
  • NASH
  • peroxisome proliferator-activated receptor (PPAR)
  • Liver Diseases
  • Fibrosis
  • Fatty Liver
  • Non-alcoholic Fatty Liver Disease
  • Digestive System Diseases
  • IVA337
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
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

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.
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
247 participants (actual)

Study arms

  • Experimental
    IVA337 1200mg

    IVA337 400mg, once a day (Quaque Die, QD) with food

    Drug: IVA337

  • Experimental
    IVA337 800mg

    IVA337 400mg, once a day (Quaque Die, QD) with food

    Drug: IVA337

  • Placebo comparator
    Placebo

    Placebo to match, once a day (Quaque Die, QD) with food

    Drug: Placebo

Interventions

  • DrugIVA337

    1200mg

  • DrugIVA337

    800mg

  • DrugPlacebo

    Placebo to match

05

What researchers measure

Primary outcomes

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

    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

Secondary outcomes

  1. NASH Improvement

    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

  2. NASH Resolution and no Worsening of Fibrosis

    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

  3. Improvement of Fibrosis by at Least 1 Stage and no Worsening of NASH

    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

  4. Activity (SAF-A) Improvement

    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

  5. Steatosis (CRN-S) Improvement

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

    Time frame: 24 weeks

  6. Lobular Inflammation (CRN-I) Improvement

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

    Time frame: 24 weeks

  7. Hepatocyte Balooning (CRN-B) Improvement

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

    Time frame: 24 weeks

  8. Fibrosis (CRN-F) Improvement

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

    Time frame: 24 weeks

  9. Modified ISHAK Fibrosis (ISHAK-F) Improvement

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

    Time frame: 24 weeks

  10. Absolute Change in ALT

    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

  11. Absolute Change in AST

    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

  12. Absolute Change in GGT

    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

  13. Absolute Change in Fibrinogen

    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

  14. Absolute Change in Hs-CRP

    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

  15. Absolute Change in Alpha2 Macroglobulin

    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

  16. Absolute Change in Haptoglobulin

    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

  17. Absolute Change of Fasting Plasma Glucose

    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

  18. Absolute Change in Insulin

    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

  19. Absolute Change in HOMA Index

    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

  20. Absolute Change in HbA1c

    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

  21. Absolute Change in Total Cholesterol

    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

  22. Absolute Change of HDL-Cholesterol

    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

  23. Absolute Change of LDL-Cholesterol

    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

  24. Absolute Change in Triglycerides

    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

  25. Absolute Change in Apo A1

    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

  26. Absolute Change in Adiponectin

    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

  27. Resolution of NASH and Improvement of Fibrosis by at Least 1 Stage

    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.

06

Results

Posted Apr 12, 2021

Participant flow

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.

Participant flow — Overall Study
MilestoneLanifibranor 1200mgLanifibranor 800mgPlacebo
Started838381
Completed777774
Not completed667
Withdrew: Adverse event333
Withdrew: Lost to follow-up110
Withdrew: Non compliance011
Withdrew: Withdrawal by patient and adverse event non fatal010
Withdrew: Withdrawal by subject201
Withdrew: Use of prohibited drug002

Outcome measures

PrimarySAF Activity Score (SAF-A) Decrease of at Least 2 Points With no Worsening of the CRN Fibrosis Score (CRN-F)

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
Reported as:
Count of participants · Participants
SAF Activity Score (SAF-A) Decrease of at Least 2 Points With no Worsening of the CRN Fibrosis Score (CRN-F)
ParticipantsIVA337 1200mgIVA337 800mgPlacebo
Yes413422
No424959
Statistical analysis
  • IVA337 800mg vs Placebo · Cochran-Mantel-Haenszel · p = =0.061 · Risk ratio (rr): 1.52 · 95% CI 0.98 to 2.12
  • IVA337 1200mg vs Placebo · Cochran-Mantel-Haenszel · p = =0.004 · Risk ratio (rr): 1.82 · 95% CI 1.24 to 2.4
SecondaryNASH Improvement

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
Reported as:
Count of participants · Participants
NASH Improvement
ParticipantsIVA337 1200mgIVA337 800mgPlacebo
Yes534326
No304055
SecondaryNASH Resolution and no Worsening of Fibrosis

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
Reported as:
Count of participants · Participants
NASH Resolution and no Worsening of Fibrosis
ParticipantsIVA337 1200mgIVA337 800mgPlacebo
Yes372715
No465666
SecondaryImprovement of Fibrosis by at Least 1 Stage and no Worsening of NASH

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
Reported as:
Count of participants · Participants
Improvement of Fibrosis by at Least 1 Stage and no Worsening of NASH
ParticipantsIVA337 1200mgIVA337 800mgPlacebo
Yes352319
No486062
SecondaryActivity (SAF-A) Improvement

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
Reported as:
Count of participants · Participants
Activity (SAF-A) Improvement
ParticipantsIVA337 1200mgIVA337 800mgPlacebo
Yes625440
No212941
SecondarySteatosis (CRN-S) Improvement

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

Time frame:
24 weeks
Reported as:
Count of participants · Participants
Steatosis (CRN-S) Improvement
ParticipantsIVA337 1200mgIVA337 800mgPlacebo
Yes544621
No293760
SecondaryLobular Inflammation (CRN-I) Improvement

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

Time frame:
24 weeks
Reported as:
Count of participants · Participants
Lobular Inflammation (CRN-I) Improvement
ParticipantsIVA337 1200mgIVA337 800mgPlacebo
Yes433430
No404951
SecondaryHepatocyte Balooning (CRN-B) Improvement

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

Time frame:
24 weeks
Reported as:
Count of participants · Participants
Hepatocyte Balooning (CRN-B) Improvement
ParticipantsIVA337 1200mgIVA337 800mgPlacebo
Yes605437
No232944
SecondaryFibrosis (CRN-F) Improvement

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

Time frame:
24 weeks
Reported as:
Count of participants · Participants
Fibrosis (CRN-F) Improvement
ParticipantsIVA337 1200mgIVA337 800mgPlacebo
Yes362822
No475559
SecondaryModified ISHAK Fibrosis (ISHAK-F) Improvement

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

Time frame:
24 weeks
Reported as:
Count of participants · Participants
Modified ISHAK Fibrosis (ISHAK-F) Improvement
ParticipantsIVA337 1200mgIVA337 800mgPlacebo
Yes413225
No425156
SecondaryAbsolute Change in ALT

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
Reported as:
Mean · U/L
Absolute Change in ALT
U/LIVA337 1200mgIVA337 800mgPlacebo
Absolute Change in ALT-24.54 ± 3.82-26.08 ± 3.85-1.4 ± 3.88
SecondaryAbsolute Change in AST

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
Reported as:
Mean · U/L
Absolute Change in AST
U/LIVA337 1200mgIVA337 800mgPlacebo
Absolute Change in AST-12.04 ± 3.17-15.11 ± 3.2-0.08 ± 3.22
SecondaryAbsolute Change in GGT

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
Reported as:
Mean · U/L
Absolute Change in GGT
U/LIVA337 1200mgIVA337 800mgPlacebo
Absolute Change in GGT-27.87 ± 5.57-43.38 ± 5.614.41 ± 5.65
SecondaryAbsolute Change in Fibrinogen

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
Reported as:
Mean · g/L
Absolute Change in Fibrinogen
g/LIVA337 1200mgIVA337 800mgPlacebo
Absolute Change in Fibrinogen-0.14 ± 0.81-0.10 ± 0.610.02 ± 0.67
SecondaryAbsolute Change in Hs-CRP

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
Reported as:
Mean · mg/L
Absolute Change in Hs-CRP
mg/LIVA337 1200mgIVA337 800mgPlacebo
Absolute Change in Hs-CRP-1.37 ± 0.46-2.05 ± 0.470.11 ± 0.47
SecondaryAbsolute Change in Alpha2 Macroglobulin

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
Reported as:
Mean · g/L
Absolute Change in Alpha2 Macroglobulin
g/LIVA337 1200mgIVA337 800mgPlacebo
Absolute Change in Alpha2 Macroglobulin0.13 ± 0.380.15 ± 0.400.05 ± 0.35
SecondaryAbsolute Change in Haptoglobulin

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
Reported as:
Mean · g/L
Absolute Change in Haptoglobulin
g/LIVA337 1200mgIVA337 800mgPlacebo
Absolute Change in Haptoglobulin-0.099 ± 0.378-0.053 ± 0.2560.074 ± 0.291
SecondaryAbsolute Change of Fasting Plasma Glucose

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
Reported as:
Mean · mmol/L
Absolute Change of Fasting Plasma Glucose
mmol/LIVA337 1200mgIVA337 800mgPlacebo
Absolute Change of Fasting Plasma Glucose-0.6 ± 0.12-0.78 ± 0.120.24 ± 0.12
SecondaryAbsolute Change in Insulin

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
Reported as:
Mean · pmol/L
Absolute Change in Insulin
pmol/LIVA337 1200mgIVA337 800mgPlacebo
Absolute Change in Insulin-114.91 ± 11.75-118.66 ± 11.66-35.7 ± 11.6
SecondaryAbsolute Change in HOMA Index

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
Reported as:
Mean · index
Absolute Change in HOMA Index
indexIVA337 1200mgIVA337 800mgPlacebo
Absolute Change in HOMA Index-5.46 ± 0.58-5.79 ± 0.58-1.47 ± 0.57
SecondaryAbsolute Change in HbA1c

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
Reported as:
Mean · percentage
Absolute Change in HbA1c
percentageIVA337 1200mgIVA337 800mgPlacebo
Absolute Change in HbA1c-0.41 ± 0.05-0.38 ± 0.050.07 ± 0.05
SecondaryAbsolute Change in Total Cholesterol

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
Reported as:
Mean · mmol/L
Absolute Change in Total Cholesterol
mmol/LIVA337 1200mgIVA337 800mgPlacebo
Absolute Change in Total Cholesterol-0.07 ± 0.07-0.02 ± 0.080.01 ± 0.08
SecondaryAbsolute Change of HDL-Cholesterol

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
Reported as:
Mean · mmol/L
Absolute Change of HDL-Cholesterol
mmol/LIVA337 1200mgIVA337 800mgPlacebo
Absolute Change of HDL-Cholesterol0.11 ± 0.020.16 ± 0.020.01 ± 0.02
SecondaryAbsolute Change of LDL-Cholesterol

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
Reported as:
Mean · mmol/L
Absolute Change of LDL-Cholesterol
mmol/LIVA337 1200mgIVA337 800mgPlacebo
Absolute Change of LDL-Cholesterol0.03 ± 0.070.03 ± 0.070.01 ± 0.07
SecondaryAbsolute Change in Triglycerides

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
Reported as:
Mean · mmol/L
Absolute Change in Triglycerides
mmol/LIVA337 1200mgIVA337 800mgPlacebo
Absolute Change in Triglycerides-0.44 ± 0.09-0.49 ± 0.090.06 ± 0.09
SecondaryAbsolute Change in Apo A1

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
Reported as:
Mean · mg/dL
Absolute Change in Apo A1
mg/dLIVA337 1200mgIVA337 800mgPlacebo
Absolute Change in Apo A1-4.39 ± 2.16-0.29 ± 2.190.03 ± 2.18
SecondaryAbsolute Change in Adiponectin

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
Reported as:
Mean · microgram/mL
Absolute Change in Adiponectin
microgram/mLIVA337 1200mgIVA337 800mgPlacebo
Absolute Change in Adiponectin17.12 ± 1.4411.95 ± 1.51-0.35 ± 1.44
SecondaryResolution of NASH and Improvement of Fibrosis by at Least 1 Stage

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.
Reported as:
Count of participants · Participants
Resolution of NASH and Improvement of Fibrosis by at Least 1 Stage
ParticipantsLanifibranor 1200mgLanifibranor 800mgPlacebo
Yes26176
No576675

Adverse events

Collected over On or after the first dose of treatment up to 30 days post last dose.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
IVA337 1200mg0/83 (0%)7/83 (8.4%)60/83 (72.3%)
IVA337 800mg0/83 (0%)3/83 (3.6%)48/83 (57.8%)
Placebo0/81 (0%)3/81 (3.7%)30/81 (37%)
Most frequent serious events
Showing 10 of 13
Most frequent serious events
EventIVA337 1200mgIVA337 800mgPlacebo
Post procedural haematomaInjury, poisoning and procedural complications2/831/831/81
Wrist fractureInjury, poisoning and procedural complications0/830/831/81
Cardiac failureCardiac disorders0/830/831/81
UrticariaSkin and subcutaneous tissue disorders0/830/831/81
Post procedural haemorrhageInjury, poisoning and procedural complications1/830/830/81
Procedural painInjury, poisoning and procedural complications1/830/830/81
Angina unstableCardiac disorders1/830/830/81
GastroenteritisInfections and infestations1/830/830/81
PyelonephritisInfections and infestations1/830/830/81
PancreatitisGastrointestinal disorders0/831/830/81
Most frequent other events
Most frequent other events
EventIVA337 1200mgIVA337 800mgPlacebo
FatigueGeneral disorders11/833/838/81
DiarrhoeaGastrointestinal disorders10/838/831/81
Weight increasedInvestigations7/838/830/81
NauseaGastrointestinal disorders7/838/833/81
HeadacheNervous system disorders7/834/834/81
Oedema peripheralGeneral disorders7/835/832/81
ConstipationGastrointestinal disorders5/833/836/81
DizzinessNervous system disorders6/832/833/81
Viral upper respiratory tract infectionInfections and infestations3/833/835/81
Transaminases increasedInvestigations3/835/831/81

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)IVA337 1200mgIVA337 800mgPlaceboTotal
<=18 years0000
Between 18 and 65 years676963199
>=65 years16141848
Age, Continuous
Age, Continuous(years)IVA337 1200mgIVA337 800mgPlaceboTotal
Mean52.2 ± 13.855 ± 10.453.4 ± 13.153.6 ± 12.5
Sex: Female, Male
Sex: Female, Male(Participants)IVA337 1200mgIVA337 800mgPlaceboTotal
Female495441144
Male342940103
Race (NIH/OMB)
Race (NIH/OMB)(Participants)IVA337 1200mgIVA337 800mgPlaceboTotal
American Indian or Alaska Native0022
Asian2125
Native Hawaiian or Other Pacific Islander0101
Black or African American3137
White788074232
More than one race0000
Unknown or Not Reported0000
Region of Enrollment
Region of Enrollment(participants)IVA337 1200mgIVA337 800mgPlaceboTotal
United States13111236
Czechia3238
United Kingdom3227
Mauritius2327
Switzerland0314
Spain34512
Canada3148
Austria0101
Belgium10111132
Poland1236
Italy3115
Slovenia0101
Australia37313
Bulgaria17162255
France1515939
Germany73313
07

Study locations

85 sites
  • North Alabama GI Research Center
    Madison, Alabama 35758, United States
  • ACTRI
    La Jolla, California 92037, United States
  • National Research Institute
    Los Angeles, California 90057, United States
  • Palmetto Research, LLC
    Hialeah, Florida 33016, United States
  • Florida Digestive Health Specialists, LLP
    Lakewood Ranch, Florida 34211, United States
  • Northeast GI Research Division
    Concord, Massachusetts 29027, United States
  • Duke University Medical Center
    Durham, North Carolina 27710, United States
  • Carolina's Center for Liver Disease/CHG
    Huntersville, North Carolina 28078, United States
  • Jefferson University hospital
    Philadelphia, Pennsylvania 19107, United States
  • Digestive Health Research, LLC
    Hermitage, Tennessee 37076, United States
  • The Texas Liver Institute
    San Antonio, Texas 78215, United States
  • Digestive Health Research, LLC
    San Antonio, Texas 78229, United States
  • University of Virginia Health System
    Charlottesville, Virginia 22908, United States
  • Virginia Commonwealth University
    Richmond, Virginia 23298, United States
  • Flinders Medical Centre Department of Hepatology
    Bedford Park, SA 5042, Australia
  • Monash Medical Centre
    Clayton, 3168, Australia
  • Lyell McEwin Hospital & The University of Adelaide
    Elizabeth Vale, SA 5112, Australia
  • Royal Brisbane and Women's Hospital
    Herston, Australia
  • Fiona Stanley Hospital
    Murdoch, WA 6150, Australia
  • Medical University Vienna
    Vienna, 1090, Austria
  • Hopital Erasme
    Brussels, 1070, Belgium
  • Clinique Universitaire Saint-luc
    Brussels, 1200, Belgium
  • Antwerp University Hospital
    Edegem, 2650, Belgium
  • Ziekenhuis Oost Limburg
    Genk, Belgium
  • UZ Gent
    Gent, Belgium
  • "DCC Alexandrovska", EOOD
    Sofia, Bulgaria
  • Acibadem City Clinic Tokuda Hospital
    Sofia, Bulgaria
  • Acibadem City Clinic University Hospital EOOD
    Sofia, Bulgaria
  • MHAT "Sveta Anna" Sofia
    Sofia, Bulgaria
  • Military Medical Academy - MHAT
    Sofia, Bulgaria
  • UMHAT "Sv. Ivan Rilski"
    Sofia, Bulgaria
  • UMHAT "Tsaritsa Yoanna-ISUL"
    Sofia, Bulgaria
  • University of Calgary
    Calgary, Canada
  • The Bailey Health Clinic
    Edmonton, Canada
  • CISSS de la Montérégie Centre
    Greenfield Park, Canada
  • University of Western Ontario, London Health Sciences Centre
    London, Canada
  • McGill University Health Centre (MUHC)
    Montréal, Canada
  • Medpharmgene, Inc
    Montréal, Canada
  • LAIR Centre
    Vancouver, Canada
  • Researchsite S.R.O.
    Plzen, 30100, Czechia
  • Klin Med S.R.O.
    Praha, 1200, Czechia
  • Institut klinické a experimentální medicíny, IKEM
    Praha, 14021, Czechia
  • CHU Angers
    Angers, 49933, France
  • CHRU Besançon
    Besancon, 25000, France
  • Centre Hospitalier de Bordeaux
    Bordeaux, France
  • CHU Henri Mondor
    Créteil, France
  • CHU de Grenoble
    Grenoble, France
  • Hôpital de La Croix Rousse
    Lyon, France
  • Centre Hospitalier Régional Universitaire de Montpellier
    Montpellier, France
  • CHU de Nice
    Nice, 06202, France
  • Hôpital Saint Antoine
    Paris, 75012, France
  • Hôpital La Pitié Salpétrière
    Paris, 75013, France
  • Hôpital Beaujon
    Paris, France
  • Centre Hospitalier Universitaire de Rennes
    Rennes, France
  • Hôpital de Hautepierre
    Strasbourg, France
  • Hôpital Purpan - Centre Hospitalier Universitaire (CHU) de Toulouse
    Toulouse, France
  • RWTH University Hospital
    Aachen, 52074, Germany
  • Innere Medizin II - Universitätsklinik Freiburg
    Freiburg, Germany
  • Medizinischen Klinik IV
    Heidelberg, 69120, Germany
  • Universitätsmedizin Mainz, I. Med. Klinik
    Mainz, 55131, Germany
  • Universitätsklinikum Münster
    Münster, Germany
  • University Hospital Würzburg
    Wurzburg, 97080, Germany
  • Ospedali Riuniti di Ancona-Università Politecnica delle Marche
    Ancona, 60126, Italy
  • Granda Ospedale Maggiore Policlinico - Università di Milano
    Milano, 20122, Italy
  • Pol. Giaccone
    Palermo, 90127, Italy
  • Fondazione Policlinico Agostino Gemelli
    Roma, 00168, Italy
  • Poliambulatorio Giovanni Paolo II
    San Giovanni Rotondo, Italy
  • A.O. Città della Salute e della Scienza di Torino
    Torino, 10126, Italy
  • CAP Research
    Quatre Bornes, Mauritius
  • Oddzial Gastroenterologii Hepatologii UCK
    Katowice, Poland
  • Katedra i Klinika Chorób Zakaźnych i Hepatologii Uniwersytetu Medycznego w Łodzi
    Lodz, 91-347, Poland
  • Klinika Chorób Zakaźnych
    Lublin, 20-081, Poland
  • Centrum Badan Klinicznych
    Wrocław, Poland
  • General hospital Celje
    Celje, Slovenia
  • General Hospital Murska Sobota
    Murska Sobota, Slovenia
  • Vall d'Hebron Hospital
    Barcelona, Spain
  • Hospital Puerta de Hierro MAJADAHONDA
    Madrid, 28222, Spain
  • Virgen de la Victoria University Hospital
    Malaga, 29010, Spain
  • Hospital Universitario Marqués de Valdecilla
    Santander, 39008, Spain
  • Hospital Virgen del Rocío
    Sevilla, 41013, Spain
  • Universitätsklinik für Viszerale Chirurgie und Medizin
    Bern, Switzerland
  • Epatocentro Ticino
    Lugano, 6900, Switzerland
  • Kings College Hospital NHS Foundation Trust
    London, United Kingdom
  • Freeman Hospital, Newcastle University
    Newcastle, NE7 7DN, United Kingdom
  • Nottingham University Hospitals NHS Trust
    Nottingham, United Kingdom
08

References and documents

Publications

  • Francque SM, Bedossa P, Ratziu V, Anstee QM, Bugianesi E, Sanyal AJ, Loomba R, Harrison SA, Balabanska R, Mateva L, Lanthier N, Alkhouri N, Moreno C, Schattenberg JM, Stefanova-Petrova D, Vonghia L, Rouzier R, Guillaume M, Hodge A, Romero-Gomez M, Huot-Marchand P, Baudin M, Richard MP, Abitbol JL, Broqua P, Junien JL, Abdelmalek MF; NATIVE Study Group. A Randomized, Controlled Trial of the Pan-PPAR Agonist Lanifibranor in NASH. N Engl J Med. 2021 Oct 21;385(17):1547-1558. doi: 10.1056/NEJMoa2036205. PubMed 34670042 ↗
  • Sven M F, Pierre B, Manal F A, Quentin M A, Elisabetta B, Vlad R, Philippe HM, Bruno S, Jean-Louis J, Pierre B, Jean-Louis A. A randomised, double-blind, placebo-controlled, multi-centre, dose-range, proof-of-concept, 24-week treatment study of lanifibranor in adult subjects with non-alcoholic steatohepatitis: Design of the NATIVE study. Contemp Clin Trials. 2020 Nov;98:106170. doi: 10.1016/j.cct.2020.106170. Epub 2020 Oct 8. PubMed 33038502 ↗

Study documents

  • Study protocol · Jul 9, 2019
  • Statistical analysis plan · May 13, 2020

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT03008070
Lead sponsor
Inventiva Pharma
Responsible party
Sponsor
First posted
Jan 2, 2017
Start date
Feb 7, 2017
Primary completion
Feb 20, 2020
Completion
Mar 16, 2020
Results posted
Apr 12, 2021
Last update
Jul 19, 2023

Study contacts

Sven FRANCQUE, MD, PhD
principal investigator · Division of Gastroenterology and Hepatology, Antwerp University Hospital, Wilrijkstraat 10, B-2650 Edegem, Belgium

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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