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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03008070
Ethics application status
Date submitted
22/12/2016
Date registered
2/01/2017
Date last updated
19/07/2023

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
SAF Activity Score (SAF-A) Decrease of at Least 2 Points With no Worsening of the CRN Fibrosis Score (CRN-F)
Timepoint [1] 0 0
24 weeks
Secondary outcome [1] 0 0
NASH Improvement
Timepoint [1] 0 0
24 weeks
Secondary outcome [2] 0 0
NASH Resolution and no Worsening of Fibrosis
Timepoint [2] 0 0
24 weeks
Secondary outcome [3] 0 0
Improvement of Fibrosis by at Least 1 Stage and no Worsening of NASH
Timepoint [3] 0 0
24 weeks
Secondary outcome [4] 0 0
Activity (SAF-A) Improvement
Timepoint [4] 0 0
24 weeks
Secondary outcome [5] 0 0
Steatosis (CRN-S) Improvement
Timepoint [5] 0 0
24 weeks
Secondary outcome [6] 0 0
Lobular Inflammation (CRN-I) Improvement
Timepoint [6] 0 0
24 weeks
Secondary outcome [7] 0 0
Hepatocyte Balooning (CRN-B) Improvement
Timepoint [7] 0 0
24 weeks
Secondary outcome [8] 0 0
Fibrosis (CRN-F) Improvement
Timepoint [8] 0 0
24 weeks
Secondary outcome [9] 0 0
Modified ISHAK Fibrosis (ISHAK-F) Improvement
Timepoint [9] 0 0
24 weeks
Secondary outcome [10] 0 0
Absolute Change in ALT
Timepoint [10] 0 0
24 weeks
Secondary outcome [11] 0 0
Absolute Change in AST
Timepoint [11] 0 0
24 weeks
Secondary outcome [12] 0 0
Absolute Change in GGT
Timepoint [12] 0 0
24 weeks
Secondary outcome [13] 0 0
Absolute Change in Fibrinogen
Timepoint [13] 0 0
24 weeks
Secondary outcome [14] 0 0
Absolute Change in Hs-CRP
Timepoint [14] 0 0
24 weeks
Secondary outcome [15] 0 0
Absolute Change in Alpha2 Macroglobulin
Timepoint [15] 0 0
24 weeks
Secondary outcome [16] 0 0
Absolute Change in Haptoglobulin
Timepoint [16] 0 0
24 weeks
Secondary outcome [17] 0 0
Absolute Change of Fasting Plasma Glucose
Timepoint [17] 0 0
24 weeks
Secondary outcome [18] 0 0
Absolute Change in Insulin
Timepoint [18] 0 0
24 weeks
Secondary outcome [19] 0 0
Absolute Change in HOMA Index
Timepoint [19] 0 0
24 weeks
Secondary outcome [20] 0 0
Absolute Change in HbA1c
Timepoint [20] 0 0
24 weeks
Secondary outcome [21] 0 0
Absolute Change in Total Cholesterol
Timepoint [21] 0 0
24 weeks
Secondary outcome [22] 0 0
Absolute Change of HDL-Cholesterol
Timepoint [22] 0 0
24 weeks
Secondary outcome [23] 0 0
Absolute Change of LDL-Cholesterol
Timepoint [23] 0 0
24 weeks
Secondary outcome [24] 0 0
Absolute Change in Triglycerides
Timepoint [24] 0 0
24 weeks
Secondary outcome [25] 0 0
Absolute Change in Apo A1
Timepoint [25] 0 0
24 weeks
Secondary outcome [26] 0 0
Absolute Change in Adiponectin
Timepoint [26] 0 0
24 weeks
Secondary outcome [27] 0 0
Resolution of NASH and Improvement of Fibrosis by at Least 1 Stage
Timepoint [27] 0 0
From baseline to Week 24.

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
Sex
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
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
North Carolina
Country [6] 0 0
United States of America
State/province [6] 0 0
Pennsylvania
Country [7] 0 0
United States of America
State/province [7] 0 0
Tennessee
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
United States of America
State/province [9] 0 0
Virginia
Country [10] 0 0
Austria
State/province [10] 0 0
Vienna
Country [11] 0 0
Belgium
State/province [11] 0 0
Brussels
Country [12] 0 0
Belgium
State/province [12] 0 0
Edegem
Country [13] 0 0
Belgium
State/province [13] 0 0
Genk
Country [14] 0 0
Belgium
State/province [14] 0 0
Gent
Country [15] 0 0
Bulgaria
State/province [15] 0 0
Sofia
Country [16] 0 0
Canada
State/province [16] 0 0
Calgary
Country [17] 0 0
Canada
State/province [17] 0 0
Edmonton
Country [18] 0 0
Canada
State/province [18] 0 0
Greenfield Park
Country [19] 0 0
Canada
State/province [19] 0 0
London
Country [20] 0 0
Canada
State/province [20] 0 0
Montréal
Country [21] 0 0
Canada
State/province [21] 0 0
Vancouver
Country [22] 0 0
Czechia
State/province [22] 0 0
Plzen
Country [23] 0 0
Czechia
State/province [23] 0 0
Praha
Country [24] 0 0
France
State/province [24] 0 0
Angers
Country [25] 0 0
France
State/province [25] 0 0
Besancon
Country [26] 0 0
France
State/province [26] 0 0
Bordeaux
Country [27] 0 0
France
State/province [27] 0 0
Créteil
Country [28] 0 0
France
State/province [28] 0 0
Grenoble
Country [29] 0 0
France
State/province [29] 0 0
Lyon
Country [30] 0 0
France
State/province [30] 0 0
Montpellier
Country [31] 0 0
France
State/province [31] 0 0
Nice
Country [32] 0 0
France
State/province [32] 0 0
Paris
Country [33] 0 0
France
State/province [33] 0 0
Rennes
Country [34] 0 0
France
State/province [34] 0 0
Strasbourg
Country [35] 0 0
France
State/province [35] 0 0
Toulouse
Country [36] 0 0
Germany
State/province [36] 0 0
Aachen
Country [37] 0 0
Germany
State/province [37] 0 0
Freiburg
Country [38] 0 0
Germany
State/province [38] 0 0
Heidelberg
Country [39] 0 0
Germany
State/province [39] 0 0
Mainz
Country [40] 0 0
Germany
State/province [40] 0 0
Münster
Country [41] 0 0
Germany
State/province [41] 0 0
Wurzburg
Country [42] 0 0
Italy
State/province [42] 0 0
Ancona
Country [43] 0 0
Italy
State/province [43] 0 0
Milano
Country [44] 0 0
Italy
State/province [44] 0 0
Palermo
Country [45] 0 0
Italy
State/province [45] 0 0
Roma
Country [46] 0 0
Italy
State/province [46] 0 0
San Giovanni Rotondo
Country [47] 0 0
Italy
State/province [47] 0 0
Torino
Country [48] 0 0
Mauritius
State/province [48] 0 0
Quatre Bornes
Country [49] 0 0
Poland
State/province [49] 0 0
Katowice
Country [50] 0 0
Poland
State/province [50] 0 0
Lodz
Country [51] 0 0
Poland
State/province [51] 0 0
Lublin
Country [52] 0 0
Poland
State/province [52] 0 0
Wroclaw
Country [53] 0 0
Slovenia
State/province [53] 0 0
Celje
Country [54] 0 0
Slovenia
State/province [54] 0 0
Murska Sobota
Country [55] 0 0
Spain
State/province [55] 0 0
Barcelona
Country [56] 0 0
Spain
State/province [56] 0 0
Madrid
Country [57] 0 0
Spain
State/province [57] 0 0
Malaga
Country [58] 0 0
Spain
State/province [58] 0 0
Santander
Country [59] 0 0
Spain
State/province [59] 0 0
Sevilla
Country [60] 0 0
Switzerland
State/province [60] 0 0
Bern
Country [61] 0 0
Switzerland
State/province [61] 0 0
Lugano
Country [62] 0 0
United Kingdom
State/province [62] 0 0
London
Country [63] 0 0
United Kingdom
State/province [63] 0 0
Newcastle
Country [64] 0 0
United Kingdom
State/province [64] 0 0
Nottingham

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.