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Randomized Global Phase 3 Study to Evaluate the Impact on NASH With Fibrosis of Obeticholic Acid Treatment (REGENERATE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02548351
Recruitment Status : Active, not recruiting
First Posted : September 14, 2015
Last Update Posted : April 18, 2023
Sponsor:
Information provided by (Responsible Party):
Intercept Pharmaceuticals

Study Description
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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.

Condition or disease Intervention/treatment Phase
Non Alcoholic Steatohepatitis (NASH) Drug: Obeticholic Acid Drug: Placebo Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2480 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : September 22, 2015
Estimated Primary Completion Date : September 2025
Estimated Study Completion Date : September 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: 10 mg Obeticholic Acid
10 mg Obeticholic Acid daily for the remainder of the study
 Drug: Obeticholic Acid
Experimental: 25 mg Obeticholic Acid
25 mg Obeticholic Acid daily for the remainder of the study
 Drug: Obeticholic Acid
Placebo Comparator: Placebo
One tablet daily for the remainder of the study
 Drug: Placebo


Outcome Measures
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Primary Outcome Measures :
  1. 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 [ Time Frame: Measurements at Baseline and 18 months ]

    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.

  2. 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) [ Time Frame: Time to accrue a pre-specified number of adjudicated events, End of Study, estimated to be 7 years ]

    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.



Secondary Outcome Measures :
  1. To evaluate the effect of Obeticholic Acid compared to placebo on liver histology in NASH [ Time Frame: 18 month Interim Analysis ]
    • 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

  2. To evaluate the effect of Obeticholic Acid compared to placebo on liver histology in NASH [ Time Frame: End of Study, estimated to be 7 years ]
    • 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

  3. To evaluate the effect of Obeticholic Acid compared to placebo on liver biochemistry and markers of liver function [ Time Frame: 18 months and End of Study, estimated to be 7 years ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02548351


Locations
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Sponsors and Collaborators
Intercept Pharmaceuticals
Investigators
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Study Director: Steven Shiff, MD Intercept Pharmaceuticals
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Intercept Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02548351    
Other Study ID Numbers: 747-303
First Posted: September 14, 2015    Key Record Dates
Last Update Posted: April 18, 2023
Last Verified: April 2023
Keywords provided by Intercept Pharmaceuticals:
Non Alcoholic Steatohepatitis, fatty liver disease, NASH
Additional relevant MeSH terms:
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Fatty Liver
Non-alcoholic Fatty Liver Disease
Liver Diseases
Digestive System Diseases