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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
7/02/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
16/03/2020
Sample size
Target
Accrual to date
Final
247
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
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Aachen
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Germany
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Freiburg
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Germany
State/province [38] 0 0
Heidelberg
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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
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Madrid
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Spain
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Malaga
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Spain
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Santander
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Spain
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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.

Results are available at https://clinicaltrials.gov/study/NCT03008070