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

• ClinicalTrials.gov Identifier: NCT02039219
• Recruitment Status: Terminated
• First Posted: January 17, 2014
• Results First Posted: January 28, 2020
• Last Update Posted: January 28, 2020
• Sponsor: Naga P. Chalasani
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA); Intercept Pharmaceuticals
• Information provided by (Responsible Party): Naga P. Chalasani, Indiana University School of Medicine

Study Description

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

Study Design

• 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

Arms and Interventions

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

Outcome Measures

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 ]

Eligibility Criteria

• 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

Contacts and Locations

Locations

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

• Principal Investigator: Naga Chalasani, MD; Indiana University

  Study Documents (Full-Text)

Documents provided by Naga P. Chalasani, Indiana University School of Medicine:

Study Protocol and Statistical Analysis Plan  [PDF] November 29, 2016

More Information

• 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
• Results First Posted: January 28, 2020
• Last Update Posted: January 28, 2020
• Last Verified: January 2020

Additional relevant MeSH terms:

Hepatitis A; Hepatitis; Hepatitis, Alcoholic; Liver Diseases; Digestive System Diseases; Hepatitis, Viral, Human; Virus Diseases; Infections; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Liver Diseases, Alcoholic; Alcohol-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders