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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02704403




Registration number
NCT02704403
Ethics application status
Date submitted
16/02/2016
Date registered
10/03/2016

Titles & IDs
Public title
Phase 3 Study to Evaluate the Efficacy and Safety of Elafibranor Versus Placebo in Patients With Nonalcoholic Steatohepatitis (NASH)
Scientific title
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase III Study to Evaluate the Efficacy and Safety of Elafibranor in Patients With Nonalcoholic Steatohepatitis (NASH) and Fibrosis
Secondary ID [1] 0 0
2015-005385-38
Secondary ID [2] 0 0
GFT505-315-1
Universal Trial Number (UTN)
Trial acronym
RESOLVE-IT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Nonalcoholic Steatohepatitis (NASH) With Fibrosis 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
Inflammatory and Immune System 0 0 0 0
Connective tissue diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Experimental: 120 mg Elafibranor - Coated tablets dosed at 120mg Elafibranor; oral administration; one tablet per day before breakfast with a glass of water

Placebo comparator: Placebo - Coated placebo tablets; oral administration; one tablet per day before breakfast with a glass of water

Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Elafibranor-treated Participants Relative to Placebo Achieving Resolution of Nonalcoholic Steatohepatitis Without Worsening of Fibrosis
Timepoint [1] 0 0
Measurement at 72 weeks
Primary outcome [2] 0 0
Time to Long-term Outcome Composed of All-cause Mortality, Cirrhosis, and Liver-related Clinical Outcomes
Timepoint [2] 0 0
From first randomization up to early termination of the study corresponding to 54 months (54 months being the longest duration for any given participant)
Secondary outcome [1] 0 0
Number of Elafibranor-treated Participants Relative to Placebo Achieving Improvement of Fibrosis of at Least 1 Stage
Timepoint [1] 0 0
Measurements at 72 weeks
Secondary outcome [2] 0 0
Change From Baseline of Hemoglobin A1c (HbA1c) in Diabetic Participants After 72 Weeks of Treatment in Elafibranor-treated Participants Relative to Placebo
Timepoint [2] 0 0
Measurements after 72 weeks of treatment and up to study termination
Secondary outcome [3] 0 0
Change From Baseline of High-density Lipoprotein (HDL) Cholesterol After 72 Weeks of Treatment in Elafibranor-treated Participants Relative to Placebo
Timepoint [3] 0 0
Measurements after 72 weeks of treatment and up to study termination
Secondary outcome [4] 0 0
Change From Baseline of Low-density Lipoprotein (LDL) Cholesterol After 72 Weeks of Treatment in Elafibranor-treated Participants Relative to Placebo
Timepoint [4] 0 0
Measurements after 72 weeks of treatment and up to study termination
Secondary outcome [5] 0 0
Change From Baseline of Homeostatic Model Assessment-IR (HOMA-IR) After 72 Weeks of Treatment in Elafibranor-treated Participants Relative to Placebo in Non-diabetic Participants
Timepoint [5] 0 0
Measurements after 72 weeks of treatment and up to study termination
Secondary outcome [6] 0 0
Change From Baseline of Non-high Density Lipoprotein Cholesterol After 72 Weeks of Treatment in Elafibranor-treated Participants Relative to Placebo
Timepoint [6] 0 0
Measurements after 72 weeks of treatment and up to study termination
Secondary outcome [7] 0 0
Change From Baseline of Triglycerides After 72 Weeks of Treatment in Elafibranor-treated Participants Relative to Placebo
Timepoint [7] 0 0
Measurements after 72 weeks of treatment and up to study termination

Eligibility
Key inclusion criteria
1. Males or females aged from 18 to 75 years inclusive at first screening visit.
2. Must provide signed written informed consent and agree to comply with the study protocol.
3. Females participating in this study must be of nonchildbearing potential or using highly efficient contraception for the full duration of the study and for 1 month after the end of treatment, as described below:

1. Cessation of menses for at least 12 months due to ovarian failure,
2. Surgical sterilization such as bilateral oopherectomy, hysterectomy, or medically documented ovarian failure
3. If requested by local IRB regulations and/or National laws, sexual abstinence may be considered adequate (the reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient)
4. Using a highly effective nonhormonal method of contraception (bilateral tubal occlusion, vasectomized partner, or intra-uterine device)
5. Double contraception with barrier AND highly effective hormonal method of contraception (oral, intravaginal, or transdermal combined estrogen and progestogen hormonal contraception associated with inhibition of ovulation; oral, injectable, or implantable progestogen-only hormonal contraception associated with inhibition of ovulation; or intrauterine hormone-releasing system). The hormonal contraception must be started at least 1 month prior to Randomization.
4. Histological confirmation of steatohepatitis on a diagnostic liver biopsy by central reading of the slides (biopsy obtained within 6 months prior to randomization or during the screening period) with at least 1 in each component of the NAS score (steatosis scored 0-3, ballooning degeneration scored 0-2, and lobular inflammation scored 0-3).
5. NAS score =4.
6. Fibrosis stage of 1 or greater and below 4, according to the NASH CRN fibrosis staging system.
7. Stable dose of vitamin E, polyunsaturated fatty acids, or ursodeoxycholic acid from at least 6 months prior to diagnostic liver biopsy
8. For participants with type 2 diabetes, glycemia must be controlled. If glycemia is controlled by antidiabetic drugs, change in anti-diabetic therapy must follow these requirements:

1. No qualitative change 6 months prior to diagnostic liver biopsy up to Randomization (i.e., implementation of a new anti-diabetic therapy) for participants treated with metformin, gliptins, sulfonylureas, sodium/glucose cotransporter (SGLT) 2 inhibitors, glucagon-like peptide (GLP)-1 agonists, or insulin. Dose changes of these medications are allowed in the 6 months prior to diagnostic liver biopsy, except for GLP-1 agonists, which must remain on stable dose in the 6 months prior to diagnostic liver biopsy.
2. No implementation of GLP-1 agonists and SGLT2 inhibitors up to 72 weeks of treatment (Visit 7).

Initiation of any other antidiabetic drugs is allowed after Randomization based on treating physicians' judgment, except for glitazones which are prohibited 6 months prior to diagnostic liver biopsy until the end of treatment.
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Known heart failure (Grade I to IV of New York Heart Association classification).
2. History of efficient bariatric surgery within 5 years prior to screening.
3. Uncontrolled hypertension during the Screening Period despite optimal antihypertensive therapy
4. Type 1 diabetes participants .
5. Participants with decompensated diabetes (HbA1c>9%).
6. Participants with a history of clinically significant acute cardiac event within 6 months prior to screening
7. Weight loss of more than 5% within 6 months prior to randomization
8. Compensated and decompensated cirrhosis
9. Current or recent history (<5 years) of significant alcohol consumption
10. Pregnant or lactating females or females planning to become pregnant during the study period.
11. Other well documented causes of chronic liver disease according to standard diagnostic procedures
12. Participants with previous exposure to Elafibranor
13. Prohibited concomitant medication
14. Any medical conditions that may diminish life expectancy to less than 2 years including known cancers.
15. Evidence of any other unstable or untreated clinically significant immunological, endocrine, hematological, gastrointestinal, neurological, neoplastic or psychiatric disease.
16. Mental instability or incompetence, such that the validity of informed consent or ability to be compliant with the study is uncertain.
17. Participants with biological criteria exclusion as per effective protocol

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 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
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 - Bedford Park
Recruitment hospital [2] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [3] 0 0
Monash Medical Centre Clayton - Clayton
Recruitment hospital [4] 0 0
Concord Repatriation General Hospital - Concord
Recruitment hospital [5] 0 0
St. Vincent's Hospital Melbourne - Fitzroy
Recruitment hospital [6] 0 0
Austin Hospital - Heidelberg
Recruitment hospital [7] 0 0
Nepean Hospital - Kingswood
Recruitment hospital [8] 0 0
The St George Hospital - Kogarah
Recruitment hospital [9] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [10] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [11] 0 0
Sir Charles Gairdner Hospital (SCGH) - Nedlands
Recruitment hospital [12] 0 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 0 0
5042 - Bedford Park
Recruitment postcode(s) [2] 0 0
3128 - Box Hill
Recruitment postcode(s) [3] 0 0
3168 - Clayton
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2139 - Concord
Recruitment postcode(s) [5] 0 0
3065 - Fitzroy
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3084 - Heidelberg
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2747 - Kingswood
Recruitment postcode(s) [8] 0 0
2217 - Kogarah
Recruitment postcode(s) [9] 0 0
3004 - Melbourne
Recruitment postcode(s) [10] 0 0
6150 - Murdoch
Recruitment postcode(s) [11] 0 0
6009 - Nedlands
Recruitment postcode(s) [12] 0 0
2145 - Westmead
Recruitment outside Australia
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United States of America
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Illinois
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Kentucky
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Louisiana
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Maryland
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Massachusetts
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Bonn
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Hannover
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Heidelberg
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Köln
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Roma
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DIF
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Spain
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Santander
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Sevilla
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Sweden
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Stockholm
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Switzerland
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Bern
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Switzerland
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Lausanne
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Switzerland
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Saint Gallen
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Switzerland
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Zurich
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Turkey
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Ankara
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Turkey
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Fatih
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Turkey
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Istanbul
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Turkey
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Izmir
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Turkey
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Pendik
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Turkey
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Çapa
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United Kingdom
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Birmingham
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United Kingdom
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Cambridge
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United Kingdom
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Frimley
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United Kingdom
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Hull
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London
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Newcastle upon Tyne
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Nottingham
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United Kingdom
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Plymouth
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United Kingdom
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Portsmouth

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Carol Addy, MD MMSc
Address 0 0
Genfit
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.