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

Primary Purpose

Alcoholic Hepatitis

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Placebo
10 mg Obeticholic Acid (OCA)
Sponsored by
Naga P. Chalasani
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alcoholic Hepatitis

Eligibility Criteria

21 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Indiana University
  • Mayo Clinic
  • Einstein Healthcare Network
  • Virgina Commonwealth University

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

10 mg Obeticholic Acid (OCA)

Arm Description

Placebo

10 mg Obeticholic Acid (OCA) Study medication will be administered orally, once daily for 6 weeks.

Outcomes

Primary Outcome Measures

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.
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).
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.

Secondary Outcome Measures

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).
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).
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).
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.
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.
Percentage of Participants Deceased at Day 42, 90 and 180
Number of subjects deceased at day 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).
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.
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.
Length of Hospital Stays
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.
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.
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.
Discontinuation Rate During the Treatment and Follow-up Phases

Full Information

First Posted
January 15, 2014
Last Updated
January 16, 2020
Sponsor
Naga P. Chalasani
Collaborators
National Institute on Alcohol Abuse and Alcoholism (NIAAA), Intercept Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT02039219
Brief Title
Trial of Obeticholic Acid in Patients With Moderately Severe Alcoholic Hepatitis (AH)
Acronym
TREAT
Official Title
A Double-Blind, Placebo-Controlled Trial of Obeticholic Acid in Patients With Moderately Severe Alcoholic Hepatitis (AH)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2020
Overall Recruitment Status
Terminated
Why Stopped
Post-marketing reports of hepatotoxicity associated with obeticholic acid emerged in June 2017, investigators temporarily halted patient recruitment June 2017.
Study Start Date
November 3, 2014 (Actual)
Primary Completion Date
July 30, 2017 (Actual)
Study Completion Date
January 29, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Naga P. Chalasani
Collaborators
National Institute on Alcohol Abuse and Alcoholism (NIAAA), Intercept Pharmaceuticals

4. Oversight

Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alcoholic Hepatitis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
19 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo
Arm Title
10 mg Obeticholic Acid (OCA)
Arm Type
Experimental
Arm Description
10 mg Obeticholic Acid (OCA) Study medication will be administered orally, once daily for 6 weeks.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
1 tablet of placebo, taken orally daily with water, approximately 30 minutes prior to breakfast for 6 weeks.
Intervention Type
Drug
Intervention Name(s)
10 mg Obeticholic Acid (OCA)
Other Intervention Name(s)
INT-747
Intervention Description
10 mg Obeticholic Acid (OCA) Study medication will be administered orally, once daily, approximately 30 minutes prior to breakfast for 6 weeks.
Primary Outcome Measure Information:
Title
MELD Score Mean(SD)
Description
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.
Time Frame
Baseline to 6 weeks (Day 42)
Title
Incidence of Serious Adverse Events (SAEs) During the Treatment Phase
Description
Number of subjects with one or more SAE are reported in relation to study medication (not related, unlikely, possible, probable, definite).
Time Frame
Baseline to 6 weeks (Day 42)
Title
MELD Score Change From Baseline Mean(SD)
Description
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.
Time Frame
Baseline to 6 weeks (Day 42)
Secondary Outcome Measure Information:
Title
Any SAEs During the Follow-up Phase
Description
Number of subjects with one or more SAE are reported in relation to study medication (not related, unlikely, possible, probable, definite).
Time Frame
Days 42 to 180
Title
SAEs Attributable to the Study Medicine During the Treatment and Follow-up Phases
Description
Number of subjects with one or more SAE are reported in relation to study medication (not related, unlikely, possible, probable, definite).
Time Frame
Baseline to 180 days
Title
Adverse Events (AEs) During the Treatment and Follow-up Phases
Description
Number of subjects with one or more AEs are reported in relation to study medication (not related, unlikely, possible, probable, definite).
Time Frame
Baseline to 180 days
Title
Change in MELD Score at 90 and 180 Days
Description
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.
Time Frame
Days 90 and 180
Title
Change in Child-Pugh Score at Day 42, 90 and 180 Days
Description
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.
Time Frame
Days 42, 90 and 180
Title
Percentage of Participants Deceased at Day 42, 90 and 180
Description
Number of subjects deceased at day 42, 90, and 180.
Time Frame
Days 42, 90 and 180
Title
Rates of Hospitalization
Description
Number of subjects with one or more hospitalization are reported in relation to study medication (not related, unlikely, possible, probable, definite).
Time Frame
Baseline to 180 days
Title
Changes in Intestinal Inflammation
Description
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.
Time Frame
Baseline to Day 180
Title
Changes in Serum Oxidative Stress.
Description
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.
Time Frame
Baseline to 180 days
Title
Length of Hospital Stays
Time Frame
Baseline to 180 days
Title
Changes in Bacterial Translocation
Description
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.
Time Frame
Baseline to 180 days
Title
Changes in Cytokines
Description
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.
Time Frame
Baseline to 180 days
Title
Changes in Activation of Innate Immunity
Description
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.
Time Frame
Baseline to 180 days
Title
Discontinuation Rate During the Treatment and Follow-up Phases
Time Frame
Baseline to 180 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Naga Chalasani, MD
Organizational Affiliation
Indiana University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Indiana University
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Einstein Healthcare Network
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19141
Country
United States
Facility Name
Virgina Commonwealth University
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States

12. IPD Sharing Statement

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

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