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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

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.

Condition or disease Intervention/treatment Phase
Alcoholic Hepatitis Drug: Placebo Drug: 10 mg Obeticholic Acid (OCA) Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-Blind, Placebo-Controlled Trial of Obeticholic Acid in Patients With Moderately Severe Alcoholic Hepatitis (AH)
Actual Study Start Date : November 3, 2014
Actual Primary Completion Date : July 30, 2017
Actual Study Completion Date : January 29, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Placebo
Placebo
Drug: Placebo
1 tablet of placebo, taken orally daily with water, approximately 30 minutes prior to breakfast for 6 weeks.

Experimental: 10 mg Obeticholic Acid (OCA)
10 mg Obeticholic Acid (OCA) Study medication will be administered orally, once daily 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




Primary Outcome Measures :
  1. 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.

  2. 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).

  3. 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.


Secondary Outcome Measures :
  1. 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).

  2. 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).

  3. 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).

  4. 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.

  5. 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.

  6. 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.

  7. 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).

  8. 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.

  9. 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.

  10. Length of Hospital Stays [ Time Frame: Baseline to 180 days ]
  11. 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.

  12. 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.

  13. 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.

  14. Discontinuation Rate During the Treatment and Follow-up Phases [ Time Frame: Baseline to 180 days ]


Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

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): NCT02039219


Locations
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United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Pennsylvania
Einstein Healthcare Network
Philadelphia, Pennsylvania, United States, 19141
United States, Virginia
Virgina Commonwealth University
Richmond, Virginia, United States, 23298
Sponsors and Collaborators
Naga P. Chalasani
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Intercept Pharmaceuticals
Investigators
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Principal Investigator: Naga Chalasani, MD Indiana University
  Study Documents (Full-Text)

Documents provided by Naga P. Chalasani, Indiana University School of Medicine:
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Responsible Party: Naga P. Chalasani, Naga Chalasani, MD, FACG, Indiana University School of Medicine
ClinicalTrials.gov Identifier: NCT02039219    
Other Study ID Numbers: 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 )
First Posted: January 17, 2014    Key Record Dates
Results First Posted: January 28, 2020
Last Update Posted: January 28, 2020
Last Verified: January 2020
Additional relevant MeSH terms:
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Hepatitis A
Hepatitis
Hepatitis, Alcoholic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Liver Diseases, Alcoholic
Alcohol-Induced Disorders
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders