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

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ClinicalTrials.gov Identifier: NCT02548351
Recruitment Status : Recruiting
First Posted : September 14, 2015
Last Update Posted : May 28, 2018
Sponsor:
Information provided by (Responsible Party):
Intercept Pharmaceuticals

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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 2370 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
Study Start Date : September 2015
Estimated Primary Completion Date : October 2022
Estimated Study Completion Date : October 2022


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



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, hepatocellular carcinoma (HCC), 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 months and End of Study, estimated to be 7 years ]
    • Improvement in each histological feature of NASH by at least 1 point
    • No worsening in fibrosis
    • 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 NASH as a composite endpoint
    • Resolution of fibrosis

  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

  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 ]


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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

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


Contacts
Contact: Elise Beausoleil 514-755-1894 elise.beausoleil@interceptpharma.com
Contact: Carol Parish +44 203 872 5027 carol.parish@interceptpharma.com

  Show 392 Study Locations
Sponsors and Collaborators
Intercept Pharmaceuticals
Investigators
Study Director: David Shapiro, MD Intercept Pharmaceuticals

Responsible Party: Intercept Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02548351     History of Changes
Other Study ID Numbers: 747-303
First Posted: September 14, 2015    Key Record Dates
Last Update Posted: May 28, 2018
Last Verified: May 2018

Keywords provided by Intercept Pharmaceuticals:
Non Alcoholic Steatohepatitis, fatty liver disease, NASH

Additional relevant MeSH terms:
Fatty Liver
Non-alcoholic Fatty Liver Disease
Liver Diseases
Digestive System Diseases
Chenodeoxycholic Acid
Cathartics
Gastrointestinal Agents