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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02548351




Registration number
NCT02548351
Ethics application status
Date submitted
1/09/2015
Date registered
14/09/2015
Date last updated
22/05/2020

Titles & IDs
Public title
Randomized Global Phase 3 Study to Evaluate the Impact on NASH With Fibrosis of Obeticholic Acid Treatment
Scientific title
A Phase 3, Double-Blind, Randomized, Long-Term, Placebo-Controlled, Multicenter Study Evaluating the Safety and Efficacy of Obeticholic Acid in Subjects With Nonalcoholic Steatohepatitis
Secondary ID [1] 0 0
747-303
Universal Trial Number (UTN)
Trial acronym
REGENERATE
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 - Obeticholic Acid
Treatment: Drugs - Placebo

Experimental: 10 mg Obeticholic Acid - 10 mg Obeticholic Acid daily for the remainder of the study

Experimental: 25 mg Obeticholic Acid - 25 mg Obeticholic Acid daily for the remainder of the study

Placebo Comparator: Placebo - One tablet daily for the remainder of the study


Treatment: Drugs: Obeticholic Acid


Treatment: Drugs: Placebo


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

Outcomes
Primary outcome [1] 0 0
To evaluate the effect of Obeticholic Acid compared to placebo on liver histology in non-cirrhotic nonalcoholic steatohepatitis (NASH) subjects with stage 2 or 3 fibrosis by assessing the following primary endpoints - Primary endpoints include:
The proportion of Obeticholic Acid treated patients relative to placebo achieving at least one stage of liver fibrosis improvement with no worsening of NASH, or
The proportion of Obeticholic Acid treated patients relative to placebo achieving NASH resolution with no worsening of liver fibrosis.
Timepoint [1] 0 0
Measurements at Baseline and 18 months
Primary outcome [2] 0 0
To evaluate the effect of Obeticholic Acid compared to placebo on all-cause mortality and liver-related clinical outcomes as measured by the time to first occurrence of any of the listed adjudicated events (clinical outcomes composite endpoint) - Primary endpoint events include:
Death (all cause), model of end stage liver disease (MELD) score =15, liver transplant, ascites requiring medical intervention, histological progression to cirrhosis, hospitalization (as defined by a stay of =24 hours) for onset of: variceal bleed, hepatic encephalopathy, spontaneous bacterial peritonitis.
Timepoint [2] 0 0
Time to accrue a pre-specified number of adjudicated events, End of Study, estimated to be 7 years
Secondary outcome [1] 0 0
To evaluate the effect of Obeticholic Acid compared to placebo on liver histology in NASH - Improvement of fibrosis by at lease 1 stage AND/OR resolution of NASH, without worsening of either
No worsening of fibrosis AND no worsening of NASH
Improvement in each histological feature of NASH by at least 1 point
Improvement of fibrosis by at least 2 stages
Improvement in NAS by at least 2 points with no worsening of fibrosis
Improvement of fibrosis and resolution of NASH as a composite endpoint and as defined by both endpoints being met in the same subject
Resolution of fibrosis
Histological progression to cirrhosis
Timepoint [1] 0 0
18 month Interim Analysis
Secondary outcome [2] 0 0
To evaluate the effect of Obeticholic Acid compared to placebo on liver histology in NASH - Improvement in fibrosis by at least 1 stage with no worsening of NASH
NASH resolution with no worsening of fibrosis
Improvement of fibrosis by at lease 1 stage AND/OR resolution of NASH, without worsening of either
No worsening of fibrosis AND no worsening of NASH
Improvement in each histological feature of NASH by at least 1 point
Improvement of fibrosis by at least 2 stages
Improvement in NAS by at least 2 points with no worsening of fibrosis
Improvement of fibrosis and resolution of NASH as a composite endpoint and as defined by both endpoints being met in the same subject
Resolution of fibrosis
Timepoint [2] 0 0
End of Study, estimated to be 7 years
Secondary outcome [3] 0 0
To evaluate the effect of Obeticholic Acid compared to placebo on liver biochemistry and markers of liver function
Timepoint [3] 0 0
18 months and End of Study, estimated to be 7 years

Eligibility
Key inclusion criteria
1. Histologic evidence of NASH upon central read of a liver biopsy obtained no more than
6 months before Day 1 defined by presence of all 3 key histological features of NASH
according to NASH CRN criteria.

2. Histologic evidence of fibrosis stage 2 or stage 3 as defined by the NASH CRN scoring
of fibrosis, or

Histologic evidence of fibrosis stage 1a or stage 1b if accompanied by =1 of the
following risk factors:

- Obesity (BMI =30 kg/m2)

- Type 2 diabetes diagnosed per 2013 American Diabetes Association criteria

- ALT >1.5× upper limit of normal (ULN).

3. For subjects with a historical biopsy, is either not taking or is on stable doses of
TZDs/glitazones or vitamin E for 6 months before Day 1.

4. Stable body weight.
Minimum age
18 Years
Maximum age
85 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Model for End-stage Liver Disease (MELD) score >12

2. ALT =10× ULN

3. HbA1c >9.5%

4. Total bilirubin >1.5 mg/dL

5. Evidence of other known forms of known chronic liver disease such as alcoholic liver
disease, hepatitis B, hepatitis C, PBC, PSC, autoimmune hepatitis, Wilson disease,
iron overload, alpha-1-antitrypsin deficiency, drug-induced liver injury, known or
suspected hepatocellular carcinoma (HCC)

6. History of liver transplant, or current placement on a liver transplant list

7. Current or history of significant alcohol consumption

8. Prior or planned ileal resection, or prior or planned bariatric surgery

9. Histological presence of cirrhosis

10. History of biliary diversion

11. Known positivity for human immunodeficiency virus infection.

12. Acute cholecystitis or acute biliary obstruction.

13. BMI >45 kg/m2

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
Active, not recruiting
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
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Royal Adelaide Hospital Gastroenterology and Hepatology Dept. - Adelaide
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Flinders Medical Centre - Bedford Park
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Royal Brisbane and Women's Hospital - Brisbane
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Gallipoli Medical Research Foundation - Brisbane
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AW Morrow Gastroenterology and Liver Centre Royal Prince Alfred Hospital - Camperdown
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Monash Health - Monash Medical Centre - Clayton
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Austin Hospital - Heidelberg
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Nepean Hospital - Kingswood
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The Alfred Hospital, Department of Gastroenterology - Melbourne
Recruitment hospital [10] 0 0
Fiona Stanley Hospital - Murdoch
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The Royal Melbourne Hospital - Parkville
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Westmead Hospital - Westmead
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5000 - Adelaide
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5042 - Bedford Park
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4029 - Brisbane
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4120 - Brisbane
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2050 - Camperdown
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3168 - Clayton
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3084 - Heidelberg
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2747 - Kingswood
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3004 - Melbourne
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6150 - Murdoch
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3053 - Parkville
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2145 - Westmead
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Intercept Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The primary objectives of this study are to evaluate the effect of Obeticholic Acid treatment
compared to placebo on 1) histological improvement and 2) liver-related clinical outcomes in
patients with non-cirrhotic nonalcoholic steatohepatitis (NASH) with liver fibrosis.
Trial website
https://clinicaltrials.gov/show/NCT02548351
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Christian Weyer, MD
Address 0 0
Intercept Pharmaceuticals
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
Other publications