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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT02704403
Ethics application status
Date submitted
16/02/2016
Date registered
10/03/2016
Date last updated
30/11/2020

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
Treatment: Drugs - Elafibranor
Treatment: Drugs - Placebo

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


Treatment: Drugs: Elafibranor


Treatment: Drugs: Placebo


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

Outcomes
Primary outcome [1] 0 0
Proportion of Elafibranor treated patients relative to placebo achieving resolution of NASH without worsening of fibrosis - To evaluate the effect of Elafibranor compared to placebo on liver histology in nonalcoholic steatohepatitis (NASH) subjects with fibrosis by assessing the following endpoint: The proportion of Elafibranor treated patients relative to placebo achieving NASH resolution without worsening of fibrosis.
Timepoint [1] 0 0
Measurement at 72 weeks
Primary outcome [2] 0 0
Composite long-term outcome composed of all-cause mortality, cirrhosis, and liver-related clinical outcomes - To evaluate the effect of Elafibranor compared to placebo on composite long-term outcome measured by the number of patients with the onset of any of the adjudicated events, composed of cirrhosis, all-cause mortality, liver-related clinical outcomes.
Timepoint [2] 0 0
Time to accrue a pre-specified number of adjudicated events, estimated to be 4 years
Secondary outcome [1] 0 0
Proportion of Elafibranor treated patients relative to placebo achieving improvement of fibrosis - To evaluate the effect of Elafibranor compared to placebo on liver histology in nonalcoholic steatohepatitis (NASH) subjects by assessing the following endpoint: The proportion of Elafibranor treated patients relative to placebo achieving improvement of liver fibrosis of at least one stage.
Timepoint [1] 0 0
Measurements at 72 weeks
Secondary outcome [2] 0 0
Proportion of Elafibranor treated patients relative to placebo achieving improvement in histological scores in NASH - Percentage of patients with resolution of NASH without worsening of fibrosis (study completion)
Percentage of patients with improvement of fibrosis of at least 1 stage
Percentage of patients with at least 1 point improvement in histological scores in NASH
Timepoint [2] 0 0
Measurements after 72 weeks of treatment and up to study completion estimated at 4 years of treatment
Secondary outcome [3] 0 0
Proportion of Elafibranor treated patients relative to placebo with improvement in cardiometabolic and liver markers - To assess the following endpoints in Elafibranor treated patients relative to placebo, at Week 72 and at the end of the Long-term Treatment Period, estimated at 4 years:
cardiovascular events
changes in liver enzymes and liver markers
changes in non-invasive markers of fibrosis and steatosis
changes in lipid parameters
variation in body weight
changes in insulin resistance and glucose homeostasis markers
changes in inflammatory markers
changes in quality of life (36-Item Short-Form Health Survey [SF-36]) questionnaire)
Timepoint [3] 0 0
Measurements at Week 72, and at the end of the Long-term Treatment Period estimated at 4 years
Secondary outcome [4] 0 0
Proportion of Elafibranor treated patients relative to placebo having a liver-related death - To assess the following endpoints in Elafibranor treated patients relative to placebo, at Week 72 and at the end of the Long-term Treatment Period, estimated at 4 years:
o liver-related death
Timepoint [4] 0 0
Measurements at Week 72, and at the end of the Long-term Treatment Period estimated at 4 years

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. BMI =45 kg/m².

4. Females participating in the study must either not be of childbearing potential
(hysterectomy, bilateral oophorectomy, medically documented ovarian failure, or >50
years of age with cessation of menses for at least 12 months due to ovarian failure)
or using efficient double contraception: hormonal contraception (including patch,
contraceptive ring, etc.), intra-uterine device, or other mechanical contraception
method + condom or diaphragm or spermicide for the full duration of the study and for
1 month after the end of treatment.

5. 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).

6. NAS score =4.

7. Fibrosis stage of 1 or greater and below 4, according to the NASH CRN fibrosis staging
system.

8. Stable dose of vitamin E, polyunsaturated fatty acids, or ursodeoxycholic acid from at
least 6 months prior to diagnostic liver biopsy

9. No change in antidiabetic therapy within 6 months prior to liver biopsy
Minimum age
18 Years
Maximum age
75 Years
Gender
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

4. Type 1 diabetes patients.

5. Patients with decompensated diabetes (HbA1c>9%).

6. Patients 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. Patients 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.

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
Terminated
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)
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Flinders Medical Centre - Bedford Park
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Box Hill Hospital - Box Hill
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Monash Medical Centre Clayton - Clayton
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Concord Repatriation General Hospital - Concord
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St. Vincent's Hospital Melbourne - Fitzroy
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Austin Hospital - Heidelberg
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Nepean Hospital - Kingswood
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The St George Hospital - Kogarah
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The Alfred Hospital - Melbourne
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Fiona Stanley Hospital - Murdoch
Recruitment hospital [11] 0 0
Sir Charles Gairdner Hospital (SCGH) - Nedlands
Recruitment hospital [12] 0 0
Westmead Hospital - Westmead
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5042 - Bedford Park
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3128 - Box Hill
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3168 - Clayton
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2139 - Concord
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3065 - Fitzroy
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3084 - Heidelberg
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2747 - Kingswood
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2217 - Kogarah
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3004 - Melbourne
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6150 - Murdoch
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6009 - Nedlands
Recruitment postcode(s) [12] 0 0
2145 - Westmead
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Genfit
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The primary objectives of this study are to evaluate the effect of Elafibranor treatment
compared to placebo on 1) histological improvement and 2) all-cause mortality and
liver-related outcomes in patients with nonalcoholic steatohepatitis (NASH) and fibrosis.
Trial website
https://clinicaltrials.gov/show/NCT02704403
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pascal BIRMAN, MD
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

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02704403