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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

September 1, 2015
September 14, 2015
May 28, 2018
September 2015
October 2022   (Final data collection date for primary outcome measure)
  • 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.
  • 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.

  • Clinical outcomes composite endpoint of any of the listed adjudicated events [ Time Frame: Time to accrue a pre-specified number of adjudicated events, estimated to be 5 years ]

    Primary endpoint events include:

    Death (all cause), model of end stage liver disease (MELD) score ≥15, liver transplant, hepatocellular carcinoma (HCC), ascites, histological progression to cirrhosis, hospitalization (as defined by a stay of ≥24 hours) for onset of: variceal bleed, hepatic encephalopathy, spontaneous bacterial peritonitis.

  • Evaluate the effect of Obeticholic Acid compared to placebo on fibrosis stage in non-cirrhotic nonalcoholic steatohepatitis (NASH) subjects with stage 2 or 3 fibrosis by assessing the following co-primary endpoints [ Time Frame: Samples will be measured at Baseline and every 6 months up to 5 years ]

    Co-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
    • The proportion of Obeticholic Acid treated patients relative to placebo achieving NASH resolution with no worsening of liver fibrosis.
Complete list of historical versions of study NCT02548351 on ClinicalTrials.gov Archive Site
  • 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
  • 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
  • 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 ]
To evaluate the effect of Obeticholic Acid compared to placebo on fibrosis improvement in NASH [ Time Frame: Samples will be measured at Baseline and every 6 months up to 5 years ]

Using NASH CRN scoring criteria:

  • Improvement of fibrosis and NASH as a composite endpoint and as defined by improvement in fibrosis by at least 1 stage and improvement in nonalcoholic fatty liver disease (NAFLD) activity score (NAS) by at least 2 points.
  • Resolution of fibrosis
  • Improvement in NAS by at least 2 points with no worsening of fibrosis
Not Provided
Not Provided
 
Randomized Global Phase 3 Study to Evaluate the Impact on NASH With Fibrosis of Obeticholic Acid Treatment
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
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.
Not Provided
Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Non Alcoholic Steatohepatitis (NASH)
  • Drug: Obeticholic Acid
  • Drug: Placebo
  • Experimental: 10 mg Obeticholic Acid
    10 mg Obeticholic Acid daily for the remainder of the study
    Intervention: Drug: Obeticholic Acid
  • Experimental: 25 mg Obeticholic Acid
    25 mg Obeticholic Acid daily for the remainder of the study
    Intervention: Drug: Obeticholic Acid
  • Placebo Comparator: Placebo
    One tablet daily for the remainder of the study
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
2370
2500
October 2022
October 2022   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years to 85 Years   (Adult, Older Adult)
No
Contact: Elise Beausoleil 514-755-1894 elise.beausoleil@interceptpharma.com
Contact: Carol Parish +44 203 872 5027 carol.parish@interceptpharma.com
Australia,   Austria,   Belgium,   Canada,   Denmark,   Finland,   France,   Germany,   Hungary,   Israel,   Italy,   Netherlands,   New Zealand,   Poland,   Portugal,   Puerto Rico,   Serbia,   Spain,   Sweden,   Switzerland,   United Kingdom,   United States
 
 
NCT02548351
747-303
Yes
Not Provided
Not Provided
Intercept Pharmaceuticals
Intercept Pharmaceuticals
Not Provided
Study Director: David Shapiro, MD Intercept Pharmaceuticals
Intercept Pharmaceuticals
May 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP