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Trial of Obeticholic Acid in Patients With Moderately Severe Alcoholic Hepatitis (AH) (TREAT)

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ClinicalTrials.gov Identifier: NCT02039219
Recruitment Status : Terminated (Post-marketing reports of hepatotoxicity associated with obeticholic acid emerged in June 2017, investigators temporarily halted patient recruitment June 2017.)
First Posted : January 17, 2014
Results First Posted : January 28, 2020
Last Update Posted : January 28, 2020
Sponsor:
Collaborators:
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Intercept Pharmaceuticals
Information provided by (Responsible Party):
Naga P. Chalasani, Indiana University School of Medicine

Tracking Information
First Submitted Date  ICMJE January 15, 2014
First Posted Date  ICMJE January 17, 2014
Results First Submitted Date  ICMJE June 14, 2019
Results First Posted Date  ICMJE January 28, 2020
Last Update Posted Date January 28, 2020
Actual Study Start Date  ICMJE November 3, 2014
Actual Primary Completion Date July 30, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 16, 2020)
  • MELD Score Mean(SD) [ Time Frame: Baseline to 6 weeks (Day 42) ]
    The Model for End-Stage Liver Disease (MELD) is a numerical scale, ranging from 6 (less ill) to 40 (gravely ill), used for liver transplant candidates age 12 and older. It gives each person a 'score' (number) based on how urgently he or she needs a liver transplant within the next three months.
  • Incidence of Serious Adverse Events (SAEs) During the Treatment Phase [ Time Frame: Baseline to 6 weeks (Day 42) ]
    Number of subjects with one or more SAE are reported in relation to study medication (not related, unlikely, possible, probable, definite).
  • MELD Score Change From Baseline Mean(SD) [ Time Frame: Baseline to 6 weeks (Day 42) ]
    The Model for End-Stage Liver Disease (MELD) is a numerical scale, ranging from 6 (less ill) to 40 (gravely ill), used for liver transplant candidates age 12 and older. It gives each person a 'score' (number) based on how urgently he or she needs a liver transplant within the next three months.
Original Primary Outcome Measures  ICMJE
 (submitted: January 15, 2014)
  • Change in MELD score at 6 weeks [ Time Frame: baseline to 6 weeks ]
  • Incidence of Serious Adverse Events (SAEs) During the Treatment Phase [ Time Frame: baseline to 6 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 16, 2020)
  • Any SAEs During the Follow-up Phase [ Time Frame: Days 42 to 180 ]
    Number of subjects with one or more SAE are reported in relation to study medication (not related, unlikely, possible, probable, definite).
  • SAEs Attributable to the Study Medicine During the Treatment and Follow-up Phases [ Time Frame: Baseline to 180 days ]
    Number of subjects with one or more SAE are reported in relation to study medication (not related, unlikely, possible, probable, definite).
  • Adverse Events (AEs) During the Treatment and Follow-up Phases [ Time Frame: Baseline to 180 days ]
    Number of subjects with one or more AEs are reported in relation to study medication (not related, unlikely, possible, probable, definite).
  • Change in MELD Score at 90 and 180 Days [ Time Frame: Days 90 and 180 ]
    The Model for End-Stage Liver Disease (MELD) is a numerical scale, ranging from 6 (less ill) to 40 (gravely ill), used for liver transplant candidates age 12 and older. It gives each person a 'score' (number) based on how urgently he or she needs a liver transplant within the next three months.
  • Change in Child-Pugh Score at Day 42, 90 and 180 Days [ Time Frame: Days 42, 90 and 180 ]
    The Child-Pugh score is a system for assessing the prognosis - including the required strength of treatment and necessity of liver transplant - of chronic liver disease, primarily cirrhosis. It provides a forecast of the increasing severity of your liver disease and your expected survival rate. The Child-Pugh score is determined by scoring five clinical measures of liver disease. A score of 1, 2, or 3 is given to each measure, with 3 being the most severe. The total Child-Pugh range is 5-15, with 15 being the most severe.
  • Percentage of Participants Deceased at Day 42, 90 and 180 [ Time Frame: Days 42, 90 and 180 ]
    Number of subjects deceased at day 42, 90, and 180.
  • Rates of Hospitalization [ Time Frame: Baseline to 180 days ]
    Number of subjects with one or more hospitalization are reported in relation to study medication (not related, unlikely, possible, probable, definite).
  • Changes in Intestinal Inflammation [ Time Frame: Baseline to Day 180 ]
    Early termination of the study resulted in insufficient numbers of participants in each arm to allow meaningful assessment of obeticholic acid effects on these secondary outcomes. Therefore these endpoints were not measured and no statistical analysis for these endpoints was done as they endpoints were not measured.
  • Changes in Serum Oxidative Stress. [ Time Frame: Baseline to 180 days ]
    Early termination of the study resulted in insufficient numbers of participants in each arm to allow meaningful assessment of obeticholic acid effects on these secondary outcomes. Therefore these endpoints were not measured and no statistical analysis for these endpoints was done as they endpoints were not measured.
  • Length of Hospital Stays [ Time Frame: Baseline to 180 days ]
  • Changes in Bacterial Translocation [ Time Frame: Baseline to 180 days ]
    Early termination of the study resulted in insufficient numbers of participants in each arm to allow meaningful assessment of obeticholic acid effects on these secondary outcomes. Therefore these endpoints were not measured and no statistical analysis for these endpoints was done as they endpoints were not measured.
  • Changes in Cytokines [ Time Frame: Baseline to 180 days ]
    Early termination of the study resulted in insufficient numbers of participants in each arm to allow meaningful assessment of obeticholic acid effects on these secondary outcomes. Therefore these endpoints were not measured and no statistical analysis for these endpoints was done as they endpoints were not measured.
  • Changes in Activation of Innate Immunity [ Time Frame: Baseline to 180 days ]
    Early termination of the study resulted in insufficient numbers of participants in each arm to allow meaningful assessment of obeticholic acid effects on these secondary outcomes. Therefore these endpoints were not measured and no statistical analysis for these endpoints was done as they endpoints were not measured.
  • Discontinuation Rate During the Treatment and Follow-up Phases [ Time Frame: Baseline to 180 days ]
Original Secondary Outcome Measures  ICMJE
 (submitted: January 15, 2014)
  • Any SAEs During the Follow-up Phase [ Time Frame: Days 42 to 180 ]
  • SAEs Attributable to the Study Medicine During the Treatment and Follow-up Phases [ Time Frame: Days 42 to 180 ]
  • Adverse events (AEs) and discontinuation rates during the treatment and follow-up phases [ Time Frame: days 42 to 180 ]
  • Change in MELD score at 90 and 180 days [ Time Frame: day 90 and 180 ]
  • Change in Child-Pugh score at 6 weeks and at 90 and 180 days [ Time Frame: Days 90 and 180 ]
  • Mortality rate at Week 6 and at 90 and 180 days [ Time Frame: Week 6 and Days 90 and 180 ]
  • Rates of hospitalization and lengths of stay [ Time Frame: baseline to day 180 ]
  • Changes in intestinal permeability [ Time Frame: baseline to day 180 ]
  • Changes in intestinal inflammation and bacterial translocation [ Time Frame: Baseline to Day 180 ]
  • Changes in hepatic CYP2E1 activity [ Time Frame: baseline to day 180 ]
  • Changes in serum oxidative stress, cytokines, and activation of innate immunity. [ Time Frame: baseline to day 180 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Trial of Obeticholic Acid in Patients With Moderately Severe Alcoholic Hepatitis (AH)
Official Title  ICMJE A Double-Blind, Placebo-Controlled Trial of Obeticholic Acid in Patients With Moderately Severe Alcoholic Hepatitis (AH)
Brief Summary The main purpose of this study is to test the effectiveness of Obeticholic Acid when used in patients with moderately severe alcoholic hepatitis. The researchers suspect that individuals with alcoholic hepatitis have certain abnormalities in how their body handles bile acids (a product made by the liver on a daily basis) produced by the liver. Obeticholic acid has been shown to affect bile acid abnormalities and thus it is possible that obeticholic acid may improve liver condition in individuals with alcoholic hepatitis.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Alcoholic Hepatitis
Intervention  ICMJE
  • Drug: Placebo
    1 tablet of placebo, taken orally daily with water, approximately 30 minutes prior to breakfast for 6 weeks.
  • Drug: 10 mg Obeticholic Acid (OCA)
    10 mg Obeticholic Acid (OCA) Study medication will be administered orally, once daily, approximately 30 minutes prior to breakfast for 6 weeks.
    Other Name: INT-747
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Placebo
    Intervention: Drug: Placebo
  • Experimental: 10 mg Obeticholic Acid (OCA)
    10 mg Obeticholic Acid (OCA) Study medication will be administered orally, once daily for 6 weeks.
    Intervention: Drug: 10 mg Obeticholic Acid (OCA)
Publications * Not Provided

*   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 Terminated
Actual Enrollment  ICMJE
 (submitted: August 6, 2018)
19
Original Estimated Enrollment  ICMJE
 (submitted: January 15, 2014)
60
Actual Study Completion Date  ICMJE January 29, 2018
Actual Primary Completion Date July 30, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Individuals ≥ 21 years with a diagnosis of acute AH. The diagnosis of acute alcoholic hepatitis will be based on clinical features and testing including hepatomegaly, jaundice, fever, leukocytosis, compatible liver biochemistries in the context of heavy alcohol consumption. A liver biopsy is not mandatory, but will be required to confirm the diagnosis if a firm diagnosis of AH cannot be made on clinical and laboratory criteria
  • Moderate severity defined as MELD score > 11 and < 20
  • Heavy alcohol consumption (defined as > 40 grams per day on average in women and > 60 grams per day on average in men for a minimum of 6 months and within the 6 weeks prior to study enrollment)
  • Written informed consent
  • Negative urine pregnancy test where appropriate
  • Women of child bearing potential should be willing to practice contraception throughout the treatment period

Exclusion Criteria:

  • Significant active infection (e.g., sepsis, or spontaneous bacterial peritonitis; SBP). Subjects can be reconsidered after the infection is under control.
  • Serum creatinine > 2.5 mg/dL
  • Must not be receiving systemic steroids > 1 week at the time of Screening or any experimental medicines for AH
  • Presence of any other disease or condition that is interfering with the absorption, distribution, metabolism, or excretion of drugs including bile salt metabolism in the intestine. Patients who have undergone gastric bypass procedures will be excluded (gastric lap band is acceptable).
  • Participation in another investigational drug, biologic, or medical device trial within 30 days prior to screening
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years and older   (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 United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02039219
Other Study ID Numbers  ICMJE TREAT 002
1U01AA021840-01 ( U.S. NIH Grant/Contract )
U01AA021883 ( U.S. NIH Grant/Contract )
U01AA021891 ( U.S. NIH Grant/Contract )
U01AA021788 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Naga P. Chalasani, Indiana University School of Medicine
Study Sponsor  ICMJE Naga P. Chalasani
Collaborators  ICMJE
  • National Institute on Alcohol Abuse and Alcoholism (NIAAA)
  • Intercept Pharmaceuticals
Investigators  ICMJE
Principal Investigator: Naga Chalasani, MD Indiana University
PRS Account Indiana University
Verification Date January 2020

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