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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03439254




Registration number
NCT03439254
Ethics application status
Date submitted
14/02/2018
Date registered
20/02/2018
Date last updated
23/10/2023

Titles & IDs
Public title
Study Evaluating the Efficacy and Safety of Obeticholic Acid in Subjects With Compensated Cirrhosis Due to Nonalcoholic Steatohepatitis
Scientific title
A Phase 3, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Obeticholic Acid in Subjects With Compensated Cirrhosis Due to Nonalcoholic Steatohepatitis
Secondary ID [1] 0 0
747-304
Universal Trial Number (UTN)
Trial acronym
REVERSE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Compensated Cirrhosis 0 0
Nonalcoholic Steatohepatitis 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 - Obeticholic acid (10 mg)
Treatment: Drugs - Obeticholic acid (10 mg to 25 mg)
Treatment: Drugs - Placebo

Experimental: Obeticholic Acid (OCA) 10 mg - 10 mg OCA for up to 18 months

Experimental: Obeticholic Acid (OCA) 10 mg to 25 mg - 10 mg OCA for the first 3 months and then may titrate up to 25 mg OCA for the remaining 15 months of the study

Placebo comparator: Placebo - Placebo for up to 18 months


Treatment: Drugs: Obeticholic acid (10 mg)
Tablets administered orally once daily.

Treatment: Drugs: Obeticholic acid (10 mg to 25 mg)
Tablets administered orally once daily.

Treatment: Drugs: Placebo
Tablets administered orally once daily.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
DB Phase: Number of Participants Who Were Responders and Showed Improvement in Fibrosis by at Least 1 Stage Without Worsening of Nonalcoholic Steatohepatitis (NASH)
Timepoint [1] 0 0
Up to 18 months
Primary outcome [2] 0 0
OLE Phase: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs)
Timepoint [2] 0 0
Up to 12 months
Primary outcome [3] 0 0
OLE Phase: Change From Baseline to Month 12 in Liver Stiffness Measurement (LSM)
Timepoint [3] 0 0
Baseline and up to Month 12
Primary outcome [4] 0 0
OLE Phase: Fibrosis-4 (FIB-4) at Baseline
Timepoint [4] 0 0
Baseline (Day 1)
Primary outcome [5] 0 0
OLE Phase: Enhanced Liver Fibrosis (ELF) at Baseline
Timepoint [5] 0 0
Baseline (Day 1)
Primary outcome [6] 0 0
OLE Phase: Number of Participants Reporting All-cause Mortality
Timepoint [6] 0 0
Up to Month 12
Primary outcome [7] 0 0
OLE Phase: Number of Participants With Adjudicated Liver Related Clinical Outcomes: Ascites, Hepatocellular Carcinoma (HCC) and Non-liver Related Death
Timepoint [7] 0 0
Up to 12 months
Primary outcome [8] 0 0
OLE Phase: Number of Participants With Adjudicated Liver Related Clinical Outcomes: Worsening of Child-Pugh Score
Timepoint [8] 0 0
Up to 12 months
Primary outcome [9] 0 0
OLE Phase: Number of Participants With Adjudicated Liver Related Clinical Outcomes: Model for End-Stage Liver Disease (MELD) Score =15
Timepoint [9] 0 0
Up to 12 months
Secondary outcome [1] 0 0
DB Phase: Change From Baseline to Month 18 in LSM
Timepoint [1] 0 0
Baseline and up to Month 18
Secondary outcome [2] 0 0
DB Phase: FIB-4 at Baseline
Timepoint [2] 0 0
Baseline (Day 1)
Secondary outcome [3] 0 0
DB Phase: ELF at Baseline
Timepoint [3] 0 0
Baseline (Day 1)

Eligibility
Key inclusion criteria
Key inclusion criteria:

1. Subjects with a confirmed diagnosis of NASH and a fibrosis score of 4 based upon the NASH CRN scoring system determined by central reading

Key exclusion criteria:

1. Current or past history of a clinically evident hepatic decompensation event, such as ascites, hepatic encephalopathy (HE), or variceal bleeding
2. Current or past history of CP score =7 points
3. Model for End-stage Liver Disease (MELD) score > 12
4. ALT = 5 X ULN
5. Calculated creatinine clearance <60mL/min using Cockcroft-Gault method
6. Hemoglobin A1c (HbA1c) = 9.5 %
7. Evidence of other known forms of 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)
8. History of liver transplant, or current placement on a liver transplant list
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/08/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
8/09/2022
Sample size
Target
Accrual to date
Final
919
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Nepean Blue Mountains Local Health District, Nepean Hospital - Kingswood
Recruitment hospital [2] 0 0
Mater Misericordiae Limited - South Brisbane
Recruitment hospital [3] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [4] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [5] 0 0
St Vincent's Hospital - Fitzroy
Recruitment hospital [6] 0 0
Austin Health - Heidelberg
Recruitment hospital [7] 0 0
Royal Melbourne Hospital - Parkville
Recruitment postcode(s) [1] 0 0
2747 - Kingswood
Recruitment postcode(s) [2] 0 0
4101 - South Brisbane
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
Recruitment postcode(s) [4] 0 0
5042 - Bedford Park
Recruitment postcode(s) [5] 0 0
3065 - Fitzroy
Recruitment postcode(s) [6] 0 0
3084 - Heidelberg
Recruitment postcode(s) [7] 0 0
3050 - Parkville
Recruitment outside Australia
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Alabama
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Arizona
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Kentucky
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Maryland
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Massachusetts
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Bayern
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Hessen
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Germany
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Rheinland-Pfalz
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Sachsen
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Gdansk
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Gdynia
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Valencia
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Kyiv
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Derbyshire
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England
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Oxfordshire
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United Kingdom
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Tyne And Wear

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

Ethics approval
Ethics application status

Summary
Brief summary
The primary objective of this study is to evaluate whether obeticholic acid (OCA; INT-747) can lead to histological improvement in fibrosis with no worsening of NASH in adults with compensated cirrhosis due to NASH.
Trial website
https://clinicaltrials.gov/study/NCT03439254
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
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/NCT03439254