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

Study Overview
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Brief Summary
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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.

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

Conditions
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Alcoholic Hepatitis

Intervention / Treatment
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* Drug: Placebo
* Drug: 10 mg Obeticholic Acid (OCA)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* 1 tablet of placebo, taken orally daily with water, approximately 30 minutes prior to breakfast for 6 weeks.<br>|
| Experimental: 10 mg Obeticholic Acid (OCA)<br>10 mg Obeticholic Acid (OCA) Study medication will be administered orally, once daily for 6 weeks. | Drug: 10 mg Obeticholic Acid (OCA)<br>* 10 mg Obeticholic Acid (OCA) Study medication will be administered orally, once daily, approximately 30 minutes prior to breakfast for 6 weeks.<br>* Other names: INT-747;|

What is the study measuring?
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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 |