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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03008070




Registration number
NCT03008070
Ethics application status
Date submitted
22/12/2016
Date registered
2/01/2017
Date last updated
16/04/2020

Titles & IDs
Public title
Phase 2b Study in NASH to Assess IVA337
Scientific 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)
Secondary ID [1] 0 0
2016-001979-70
Secondary ID [2] 0 0
IVA_01_337_HNAS_16_002
Universal Trial Number (UTN)
Trial acronym
NATIVE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-Alcoholic Steatohepatitis (NASH) 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Diet and Nutrition 0 0 0 0
Obesity

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - IVA337
Treatment: Drugs - IVA337
Treatment: Drugs - Placebo

Experimental: IVA337 1200mg - IVA337 400mg, once a day (Quaque Die, QD) with food

Experimental: IVA337 800mg - IVA337 400mg, once a day (Quaque Die, QD) with food

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


Treatment: Drugs: IVA337
1200mg

Treatment: Drugs: IVA337
800mg

Treatment: Drugs: Placebo
Placebo to match

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Responder analysis based on the improvement of the SAF (steatosis: S, activity : A, and fibrosis: F) activity score. - Responder is defined as a decrease from Baseline of at least 2 points of the SAF activity score combining hepatocellular inflammation and ballooning without worsening of fibrosis
Timepoint [1] 0 0
24 weeks
Secondary outcome [1] 0 0
Percent of patients with resolution of NASH from baseline to end of treatment
Timepoint [1] 0 0
24 weeks
Secondary outcome [2] 0 0
Percent of patients with a change in components of SAF score from baseline to end of treatment : Steatosis, Lobular inflammation, Ballooning, Fibrosis
Timepoint [2] 0 0
24 weeks
Secondary outcome [3] 0 0
Change in fibrosis score on a 4-points scale (SAF score) from baseline to end of treatment
Timepoint [3] 0 0
24 weeks
Secondary outcome [4] 0 0
Change in fibrosis score on modified Ishak score from baseline to end of treatment
Timepoint [4] 0 0
24 weeks
Secondary outcome [5] 0 0
Liver enzymes change from baseline to end of treatment - Alanine amino transferase (ALT), Aspartate amino transferase (AST), Gamma glutamyl transpeptidase (?GT)
Timepoint [5] 0 0
24 weeks
Secondary outcome [6] 0 0
Inflammatory markers change from baseline to end of treatment - fibrinogen, High-sensitivity C-reactive protein (hs-CRP), alpha2 macroglobulin and haptoglobin
Timepoint [6] 0 0
24 weeks
Secondary outcome [7] 0 0
Glucose metabolism change from baseline to end of treatment - (fasting glucose and insulin, Homeostasis model assessment of insulin resistance (HOMA) index and, in subjects with type 2 diabetes mellitus (T2DM), HbA1c
Timepoint [7] 0 0
24 weeks
Secondary outcome [8] 0 0
Main plasma lipids levels change from baseline to end of treatment - Total cholesterol (TC), High-density lipoprotein cholesterol (HDL-C), calculated Low density lipoprotein cholesterol (LDL-C), Triglycerides (TG) and apoA1
Timepoint [8] 0 0
24 weeks
Secondary outcome [9] 0 0
Adiponectin change from baseline to end of treatment
Timepoint [9] 0 0
24 weeks

Eligibility
Key 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, a-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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Flinders Medical Centre Department of Hepatology - Bedford Park
Recruitment hospital [2] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [3] 0 0
Lyell McEwin Hospital & The University of Adelaide - Elizabeth Vale
Recruitment hospital [4] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [5] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 0 0
SA 5042 - Bedford Park
Recruitment postcode(s) [2] 0 0
3168 - Clayton
Recruitment postcode(s) [3] 0 0
SA 5112 - Elizabeth Vale
Recruitment postcode(s) [4] 0 0
- Herston
Recruitment postcode(s) [5] 0 0
WA 6150 - Murdoch
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
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California
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Florida
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United States of America
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Massachusetts
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United States of America
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North Carolina
Country [6] 0 0
United States of America
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Pennsylvania
Country [7] 0 0
United States of America
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Tennessee
Country [8] 0 0
United States of America
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Texas
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United States of America
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Virginia
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Austria
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Vienna
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Belgium
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Antwerp
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Belgium
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Brussels
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Belgium
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Genk
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Belgium
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Gent
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Bulgaria
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Sofia
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Canada
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Calgary
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Canada
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Edmonton
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Canada
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Greenfield Park
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London
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Vancouver
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Czechia
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Plzen
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Czechia
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Praha
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France
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Angers
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Besancon
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Heidelberg
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Mainz
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Münster
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Wurzburg
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Italy
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Ancona
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Italy
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Milano
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Italy
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Palermo
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Italy
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Roma
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Italy
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San Giovanni Rotondo
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Italy
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Torino
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Mauritius
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Phoenix
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Bialystok
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Katowice
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Lodz
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Lublin
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Wroclaw
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Slovenia
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Celje
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Murska Sobota
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Barcelona
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Santander
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Sevilla
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Switzerland
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Bern
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Switzerland
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Lugano
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United Kingdom
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Newcastle
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United Kingdom
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Nottingham

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Inventiva Pharma
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03008070
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Sven FRANCQUE, MD, PhD
Address 0 0
Division of Gastroenterology and Hepatology, Antwerp University Hospital, Wilrijkstraat 10, B-2650 Edegem, Belgium
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications