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

A Double-Blind, Placebo-Controlled Trial of Obeticholic Acid in Patients With Moderately Severe Alcoholic Hepatitis (AH)

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.

Study Overview

• Status: Terminated
• Conditions: Alcoholic Hepatitis
• Intervention / Treatment: Drug: Placebo; Drug: 10 mg Obeticholic Acid (OCA)

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19141
      • Einstein Healthcare Network
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virgina Commonwealth University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 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 Names: INT-747

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MELD Score Mean(SD)	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.	Baseline to 6 weeks (Day 42)
Incidence of Serious Adverse Events (SAEs) During the Treatment Phase	Number of subjects with one or more SAE are reported in relation to study medication (not related, unlikely, possible, probable, definite).	Baseline to 6 weeks (Day 42)
MELD Score Change From Baseline Mean(SD)	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.	Baseline to 6 weeks (Day 42)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Any SAEs During the Follow-up Phase	Number of subjects with one or more SAE are reported in relation to study medication (not related, unlikely, possible, probable, definite).	Days 42 to 180
SAEs Attributable to the Study Medicine During the Treatment and Follow-up Phases	Number of subjects with one or more SAE are reported in relation to study medication (not related, unlikely, possible, probable, definite).	Baseline to 180 days
Adverse Events (AEs) During the Treatment and Follow-up Phases	Number of subjects with one or more AEs are reported in relation to study medication (not related, unlikely, possible, probable, definite).	Baseline to 180 days
Change in MELD Score at 90 and 180 Days	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.	Days 90 and 180
Change in Child-Pugh Score at Day 42, 90 and 180 Days	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.	Days 42, 90 and 180
Percentage of Participants Deceased at Day 42, 90 and 180	Number of subjects deceased at day 42, 90, and 180.	Days 42, 90 and 180
Rates of Hospitalization	Number of subjects with one or more hospitalization are reported in relation to study medication (not related, unlikely, possible, probable, definite).	Baseline to 180 days
Changes in Intestinal Inflammation	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.	Baseline to Day 180
Changes in Serum Oxidative Stress.	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.	Baseline to 180 days
Length of Hospital Stays		Baseline to 180 days
Changes in Bacterial Translocation	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.	Baseline to 180 days
Changes in Cytokines	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.	Baseline to 180 days
Changes in Activation of Innate Immunity	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.	Baseline to 180 days
Discontinuation Rate During the Treatment and Follow-up Phases		Baseline to 180 days

Collaborators and Investigators

• Sponsor: Naga P. Chalasani
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA); Intercept Pharmaceuticals
• Investigators: Principal Investigator: Naga Chalasani, MD, Indiana University

Study record dates

Study Major Dates

• Study Start (Actual): November 3, 2014
• Primary Completion (Actual): July 30, 2017
• Study Completion (Actual): January 29, 2018

Study Registration Dates

• First Submitted: January 15, 2014
• First Submitted That Met QC Criteria: January 15, 2014
• First Posted (Estimate): January 17, 2014

Study Record Updates

• Last Update Posted (Actual): January 28, 2020
• Last Update Submitted That Met QC Criteria: January 16, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Digestive System Diseases; Alcohol-Related Disorders; Substance-Related Disorders; RNA Virus Infections; Virus Diseases; Infections; Liver Diseases; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Liver Diseases, Alcoholic; Alcohol-Induced Disorders; Hepatitis; Hepatitis A; Hepatitis, Alcoholic
• Other Study ID Numbers: TREAT 002; U01AA021891 (U.S. NIH Grant/Contract); 1U01AA021840-01 (U.S. NIH Grant/Contract); U01AA021883 (U.S. NIH Grant/Contract); U01AA021788 (U.S. NIH Grant/Contract)