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Trial record 2 of 2 for:    IVA337

Phase 2b Study in NASH to Assess IVA337 (NATIVE)

This study is currently recruiting participants.
Verified August 2017 by Inventiva Pharma
Sponsor:
ClinicalTrials.gov Identifier:
NCT03008070
First Posted: January 2, 2017
Last Update Posted: August 4, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Inventiva Pharma
  Purpose

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 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 Intervention Phase
Non-Alcoholic Steatohepatitis (NASH) Drug: IVA337 1200mg Drug: IVA337 800mg Drug: Placebo Phase 2

Study Type: Interventional
Study Design: 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)

Resource links provided by NLM:


Further study details as provided by Inventiva Pharma:

Primary Outcome Measures:
  • Responder analysis based on the improvement of the SAF (steatosis: S, activity : A, and fibrosis: F) activity score. [ Time Frame: 24 weeks ]
    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


Secondary Outcome Measures:
  • Percent of patients with reversal of NASH from baseline to end of treatment [ Time Frame: 24 weeks ]
  • Percent of patients with a change in components of SAF score from baseline to end of treatment : Steatosis, Lobular inflammation, Ballooning, Fibrosis [ Time Frame: 24 weeks ]
  • Immunohistochemistry: change in the semi quantitative score of ballooning and stellate cell activation from baseline to end of treatment [ Time Frame: 24 weeks ]
  • Change in fibrosis score on a 4-points scale (SAF score) from baseline to end of treatment [ Time Frame: 24 weeks ]
  • Change in fibrosis score on modified Ishak score from baseline to end of treatment [ Time Frame: 24 weeks ]
  • Change in fibrosis area assessed by morphometry (Collagen Proportionate Area, CPA) from baseline to end of treatment [ Time Frame: 24 weeks ]
  • Liver enzymes change from baseline to end of treatment [ Time Frame: 24 weeks ]
    Alanine amino transferase (ALT), Aspartate amino transferase (AST), Gamma glutamyl transpeptidase (γGT)

  • Inflammatory markers change from baseline to end of treatment [ Time Frame: 24 weeks ]
    fibrinogen, High-sensitivity C-reactive protein (hs-CRP), alpha2 macroglobulin and haptoglobin

  • Glucose metabolism change from baseline to end of treatment [ Time Frame: 24 weeks ]
    (fasting glucose and insulin, Homeostasis model assessment of insulin resistance (HOMA) index and, in subjects with type 2 diabetes mellitus (T2DM), HbA1c

  • Main plasma lipids levels change from baseline to end of treatment [ Time Frame: 24 weeks ]
    Total cholesterol (TC), High-density lipoprotein cholesterol (HDL-C), calculated Low density lipoprotein cholesterol (LDL-C), Triglycerides (TG) and apoA1

  • Adiponectin change from baseline to end of treatment [ Time Frame: 24 weeks ]
  • Number of participants with adverse events (AE) as a measure of safety [ Time Frame: -4, 0, 4, 10 ,14, 24 weeks ]
    Frequency and type of AEs

  • ECG data change from baseline to end of treatment [ Time Frame: -4, 4, 24 weeks ]
  • Vital signs parameters change from baseline to end of treatment [ Time Frame: -4, 0, 4, 10 ,14, 24 weeks ]

Other Outcome Measures:
  • Individual plasma through concentration of IVA337 [ Time Frame: 4 , 24 weeks ]
  • Exploratory biomarkers change from baseline to end of treatment [ Time Frame: 24 weeks ]
    inflammation, lipids, glucids, fibrosis, bone remodeling


Estimated Enrollment: 225
Study Start Date: December 2016
Estimated Study Completion Date: October 2018
Estimated Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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).

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 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, sexual abstinence)
  • Subjects must be willing to give 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.
  • 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.
  • 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).
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03008070


Contacts
Contact: Jean-Louis ABTIBOL, MD +33 (0)762203432 jean-louis.abitbol@inventivapharma.com
Contact: Nicolas ABELLO +33(0)699 025 681 nicolas.abello@inventivapharma.com

  Show 38 Study Locations
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
  More Information

Responsible Party: Inventiva Pharma
ClinicalTrials.gov Identifier: NCT03008070     History of Changes
Other Study ID Numbers: IVA_01_337_HNAS_16_002
2016-001979-70 ( EudraCT Number )
First Submitted: December 22, 2016
First Posted: January 2, 2017
Last Update Posted: August 4, 2017
Last Verified: August 2017

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
Liver Diseases
Digestive System Diseases