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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT02548351
Ethics application status
Date submitted
1/09/2015
Date registered
14/09/2015
Date last updated
1/10/2024

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
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
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time to the First Adjudicated Event for Clinical Outcome Composite Endpoint: Percentage of Participants With an Event
Timepoint [1] 0 0
Up to 7 years
Secondary outcome [1] 0 0
Percentage of Responders With Improvement of Fibrosis by at Least One Stage With no Worsening of NASH Using Consensus Read Method of Scheduled Liver Biopsies
Timepoint [1] 0 0
Up to 7 years
Secondary outcome [2] 0 0
Percentage of Participants Who Showed Improvement in Fibrosis by at Least 1 Stage and/or Resolution of NASH Without Worsening of Either Using Consensus Read Method
Timepoint [2] 0 0
Up to 7 years
Secondary outcome [3] 0 0
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Timepoint [3] 0 0
Up to 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
Sex
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
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/09/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
15/09/2023
Sample size
Target
Accrual to date
Final
2477
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Royal Adelaide Hospital Gastroenterology and Hepatology Dept. - Adelaide
Recruitment hospital [2] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [3] 0 0
AW Morrow Gastroenterology and Liver Centre Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [4] 0 0
Monash Health - Monash Medical Centre - Clayton
Recruitment hospital [5] 0 0
Gallipoli Medical Research Foundation - Greenslopes
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Austin Hospital - Heidelberg
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Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [8] 0 0
Nepean Hospital - Kingswood
Recruitment hospital [9] 0 0
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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2050 - Camperdown
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3168 - Clayton
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4120 - Greenslopes
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3084 - Heidelberg
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4029 - Herston
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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/study/NCT02548351
Trial related presentations / publications
Rinella ME, Dufour JF, Anstee QM, Goodman Z, Younossi Z, Harrison SA, Loomba R, Sanyal AJ, Bonacci M, Trylesinski A, Natha M, Shringarpure R, Granston T, Venugopal A, Ratziu V. Non-invasive evaluation of response to obeticholic acid in patients with NASH: Results from the REGENERATE study. J Hepatol. 2022 Mar;76(3):536-548. doi: 10.1016/j.jhep.2021.10.029. Epub 2021 Nov 15.
Younossi ZM, Stepanova M, Nader F, Loomba R, Anstee QM, Ratziu V, Harrison S, Sanyal AJ, Schattenberg JM, Barritt AS, Noureddin M, Bonacci M, Cawkwell G, Wong B, Rinella M; RandomizEd Global Phase 3 Study to Evaluate the Impact on NASH with FibRosis of Obeticholic Acid TreatmEnt (REGENERATE) Study Investigators. Obeticholic Acid Impact on Quality of Life in Patients With Nonalcoholic Steatohepatitis: REGENERATE 18-Month Interim Analysis. Clin Gastroenterol Hepatol. 2022 Sep;20(9):2050-2058.e12. doi: 10.1016/j.cgh.2021.07.020. Epub 2021 Jul 15.
Younossi ZM, Ratziu V, Loomba R, Rinella M, Anstee QM, Goodman Z, Bedossa P, Geier A, Beckebaum S, Newsome PN, Sheridan D, Sheikh MY, Trotter J, Knapple W, Lawitz E, Abdelmalek MF, Kowdley KV, Montano-Loza AJ, Boursier J, Mathurin P, Bugianesi E, Mazzella G, Olveira A, Cortez-Pinto H, Graupera I, Orr D, Gluud LL, Dufour JF, Shapiro D, Campagna J, Zaru L, MacConell L, Shringarpure R, Harrison S, Sanyal AJ; REGENERATE Study Investigators. Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial. Lancet. 2019 Dec 14;394(10215):2184-2196. doi: 10.1016/S0140-6736(19)33041-7. Epub 2019 Dec 5. Erratum In: Lancet. 2020 Aug 1;396(10247):312. doi: 10.1016/S0140-6736(20)31645-7. Lancet. 2021 Jun 19;397(10292):2336. doi: 10.1016/S0140-6736(21)01216-2.
Ratziu V, Sanyal AJ, Loomba R, Rinella M, Harrison S, Anstee QM, Goodman Z, Bedossa P, MacConell L, Shringarpure R, Shah A, Younossi Z. REGENERATE: Design of a pivotal, randomised, phase 3 study evaluating the safety and efficacy of obeticholic acid in patients with fibrosis due to nonalcoholic steatohepatitis. Contemp Clin Trials. 2019 Sep;84:105803. doi: 10.1016/j.cct.2019.06.017. Epub 2019 Jun 29.
Public notes

Contacts
Principal investigator
Name 0 0
Sangeeta Sawhney, 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

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02548351