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Trial record 1 of 1 for:    regenerate and obeticholic
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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 : February 18, 2020
Sponsor:
Information provided by (Responsible Party):
Intercept Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE September 1, 2015
First Posted Date  ICMJE September 14, 2015
Last Update Posted Date February 18, 2020
Study Start Date  ICMJE September 2015
Estimated Primary Completion Date October 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 29, 2019)
  • 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, 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.
Original Primary Outcome Measures  ICMJE
 (submitted: September 10, 2015)
  • 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.
Change History Complete list of historical versions of study NCT02548351 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 29, 2019)
  • 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
  • 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
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 10, 2015)
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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Randomized Global Phase 3 Study to Evaluate the Impact on NASH With Fibrosis of Obeticholic Acid Treatment
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Non Alcoholic Steatohepatitis (NASH)
Intervention  ICMJE
  • Drug: Obeticholic Acid
  • Drug: Placebo
Study Arms  ICMJE
  • 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
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: September 27, 2019)
2480
Original Estimated Enrollment  ICMJE
 (submitted: September 10, 2015)
2500
Estimated Study Completion Date  ICMJE October 2022
Estimated Primary Completion Date October 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE 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
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02548351
Other Study ID Numbers  ICMJE 747-303
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Intercept Pharmaceuticals
Study Sponsor  ICMJE Intercept Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Christian Weyer, MD Intercept Pharmaceuticals
PRS Account Intercept Pharmaceuticals
Verification Date February 2020

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