NCT02039219: TREAT

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

Terminated Phase 2 Results posted Last updated 28 January 2020

What this trial tests

Phase 2 trial testing Placebo in Alcoholic Hepatitis in 19 participants. Terminated before completion.

Timeline

3 November 2014

Primary endpoint
30 July 2017

29 January 2018

Quick facts

Lead sponsor	Naga P. Chalasani
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	19
Start date	3 November 2014
Primary completion	30 July 2017
Estimated completion	29 January 2018
Sites	4 locations across United States

Drugs / interventions tested

• Placebo
• 10 mg Obeticholic Acid (OCA) — full drug profile →

Conditions studied

• Alcoholic Hepatitis — all drugs for Alcoholic Hepatitis →

Sponsor

Naga P. Chalasani

Who can join

21 and older, any sex, with Alcoholic Hepatitis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

MELD Score Mean(SD) Primary · 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.

Baseline

Group	Value	95% CI
Placebo	16.4	± 2.2
10 mg Obeticholic Acid (OCA)	14.9	± 2.4

Day 42

Group	Value	95% CI
Placebo	13.9	± 4.6
10 mg Obeticholic Acid (OCA)	11.5	± 6.8

Incidence of Serious Adverse Events (SAEs) During the Treatment Phase Primary · 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).

Not Related

Group	Value	95% CI
Placebo	5
10 mg Obeticholic Acid (OCA)	1

Unlikely

Group	Value	95% CI
Placebo	6
10 mg Obeticholic Acid (OCA)	3

Possible

Group	Value	95% CI
Placebo	0
10 mg Obeticholic Acid (OCA)	0

Probable

Group	Value	95% CI
Placebo	0
10 mg Obeticholic Acid (OCA)	0

Definite

Group	Value	95% CI
Placebo	0
10 mg Obeticholic Acid (OCA)	0

MELD Score Change From Baseline Mean(SD) Primary · 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.

Group	Value	95% CI
Placebo	-2.2	± 3.9
10 mg Obeticholic Acid (OCA)	-3.4	± 5.9

Any SAEs During the Follow-up Phase Secondary · 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).

Not Related

Group	Value	95% CI
Placebo	5
10 mg Obeticholic Acid (OCA)	5

Unlikely

Group	Value	95% CI
Placebo	3
10 mg Obeticholic Acid (OCA)	1

Possible

Group	Value	95% CI
Placebo	0
10 mg Obeticholic Acid (OCA)	0

Probable

Group	Value	95% CI
Placebo	0
10 mg Obeticholic Acid (OCA)	0

Definite

Group	Value	95% CI
Placebo	0
10 mg Obeticholic Acid (OCA)	0

SAEs Attributable to the Study Medicine During the Treatment and Follow-up Phases Secondary · 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).

Not Related

Group	Value	95% CI
Placebo	10
10 mg Obeticholic Acid (OCA)	6

Unlikely

Group	Value	95% CI
Placebo	9
10 mg Obeticholic Acid (OCA)	4

Possible

Group	Value	95% CI
Placebo	0
10 mg Obeticholic Acid (OCA)	0

Probable

Group	Value	95% CI
Placebo	0
10 mg Obeticholic Acid (OCA)	0

Definite

Group	Value	95% CI
Placebo	0
10 mg Obeticholic Acid (OCA)	0

Adverse Events (AEs) During the Treatment and Follow-up Phases Secondary · 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).

Not Related

Group	Value	95% CI
Placebo	30
10 mg Obeticholic Acid (OCA)	31

Unlikely

Group	Value	95% CI
Placebo	17
10 mg Obeticholic Acid (OCA)	25

Possible

Group	Value	95% CI
Placebo	3
10 mg Obeticholic Acid (OCA)	3

Probable

Group	Value	95% CI
Placebo	0
10 mg Obeticholic Acid (OCA)	1

Definite

Group	Value	95% CI
Placebo	0
10 mg Obeticholic Acid (OCA)	0

Change in MELD Score at 90 and 180 Days Secondary · 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.

Day 90

Group	Value	95% CI
Placebo	-4.4	± 2.8
10 mg Obeticholic Acid (OCA)	-6.0	± 4.0

Day 180

Group	Value	95% CI
Placebo	-4.0	± 5.9
10 mg Obeticholic Acid (OCA)	-4.5	± 2.3

Change in Child-Pugh Score at Day 42, 90 and 180 Days Secondary · 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.

Day 42

Group	Value	95% CI
Placebo	-1.6	± 1.9
10 mg Obeticholic Acid (OCA)	-2.8	± 1.7

Day 90

Group	Value	95% CI
Placebo	-3.0	± 1.2
10 mg Obeticholic Acid (OCA)	-3.0	± 0.6

Day 180

Group	Value	95% CI
Placebo	-2.3	± 3.0
10 mg Obeticholic Acid (OCA)	-3.5	± 0.8

Percentage of Participants Deceased at Day 42, 90 and 180 Secondary · Days 42, 90 and 180

Number of subjects deceased at day 42, 90, and 180.

Day 42

Group	Value	95% CI
Placebo	9.09
10 mg Obeticholic Acid (OCA)	0

Day 90

Group	Value	95% CI
Placebo	9.09
10 mg Obeticholic Acid (OCA)	0

Day 180

Group	Value	95% CI
Placebo	9.09
10 mg Obeticholic Acid (OCA)	0

Rates of Hospitalization Secondary · 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).

Not Related

Group	Value	95% CI
Placebo	4
10 mg Obeticholic Acid (OCA)	6

Unlikely

Group	Value	95% CI
Placebo	0
10 mg Obeticholic Acid (OCA)	0

Possible

Group	Value	95% CI
Placebo	0
10 mg Obeticholic Acid (OCA)	0

Probable

Group	Value	95% CI
Placebo	0
10 mg Obeticholic Acid (OCA)	0

Definite

Group	Value	95% CI
Placebo	0
10 mg Obeticholic Acid (OCA)	0

Length of Hospital Stays Secondary · Baseline to 180 days

Group	Value	95% CI
Placebo	1.9	± 3.3
10 mg Obeticholic Acid (OCA)	2.3	± 2.5

Discontinuation Rate During the Treatment and Follow-up Phases Secondary · Baseline to 180 days

Group	Value	95% CI
Placebo	4
10 mg Obeticholic Acid (OCA)	2

Adverse events — posted to ClinicalTrials.gov

Time frame: 6 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo

Serious: 5/11 (45%)

Deaths: 1/11

10 mg Obeticholic Acid (OCA)

Serious: 6/8 (75%)

Deaths: 0/8

Serious adverse events (23 terms)

Reaction	System	Placebo	10 mg Obeticholic Acid (OCA)
Abdominal pain	Gastrointestinal disorders	—	—
Ascites	Gastrointestinal disorders	—	—
Hyponatraemia	Metabolism and nutrition disorders	—	—
Pancreatitis acute	Gastrointestinal disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Headache	Nervous system disorders	—	—
Acute hepatic failure	Hepatobiliary disorders	—	—
Blood electrolytes abnormal	Investigations	—	—
Chronic gastrointestinal bleeding	Gastrointestinal disorders	—	—
Gastritis	Gastrointestinal disorders	—	—
Gastrointestinal haemorrhage	Gastrointestinal disorders	—	—
Haematemesis	Gastrointestinal disorders	—	—
Hallucination	Psychiatric disorders	—	—
Hydrothorax	Respiratory, thoracic and mediastinal disorders	—	—
Hyperbilirubinaemia	Hepatobiliary disorders	—	—
Hyperglycaemia	Metabolism and nutrition disorders	—	—
Kidney injury molecule-1	Investigations	—	—
Major depression	Psychiatric disorders	—	—
Pancreatitis	Gastrointestinal disorders	—	—
Peritonitis bacterial	Infections and infestations	—	—
Renal failure acute	Renal and urinary disorders	—	—
Suicidal ideation	Psychiatric disorders	—	—
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	—	—

Other adverse events (62 terms — click to expand)

Reaction	System	Placebo	10 mg Obeticholic Acid (OCA)
Nausea	Gastrointestinal disorders	—	—
Oedema peripheral	General disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Dizziness	Nervous system disorders	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Headache	Nervous system disorders	—	—
Insomnia	Psychiatric disorders	—	—
Rash	Skin and subcutaneous tissue disorders	—	—
Tachycardia	Cardiac disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Abdominal distension	Gastrointestinal disorders	—	—
Weigh Loss	Metabolism and nutrition disorders	—	—
Accidental overdose	Injury, poisoning and procedural complications	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Arrhythmia	Cardiac disorders	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—
Ascites	Gastrointestinal disorders	—	—
Cholestatic pruritus	Skin and subcutaneous tissue disorders	—	—
Clostridium difficile infection	Infections and infestations	—	—
Coagulopathy	Blood and lymphatic system disorders	—	—
Confusional state	Psychiatric disorders	—	—
Decreased Appetite	Metabolism and nutrition disorders	—	—
Electrocardiogram QT prolonged	Infections and infestations	—	—
Electrolyte imbalance	Metabolism and nutrition disorders	—	—
Escherichia urinary tract infection	Infections and infestations	—	—
Faeces pale	Gastrointestinal disorders	—	—
Fatigue	General disorders	—	—
Jittery	General disorders	—	—
Flank pain	Musculoskeletal and connective tissue disorders	—	—
Flatulence	Gastrointestinal disorders	—	—
Gastric Ulcer	Gastrointestinal disorders	—	—
Gingival bleeding	Gastrointestinal disorders	—	—
Hyperventilation	Respiratory, thoracic and mediastinal disorders	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—
Hypotension	Vascular disorders	—	—
Hypothyroidism	Endocrine disorders	—	—
Increased tendency to bruise	Blood and lymphatic system disorders	—	—
Infection	Infections and infestations	—	—

Most-reported serious reactions: Abdominal pain, Ascites, Hyponatraemia, Pancreatitis acute, Vomiting, Headache, Acute hepatic failure, Blood electrolytes abnormal.

Data from ClinicalTrials.gov NCT02039219 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Microbiota and Fatty Liver Disease-the Known, the Unknown, and the Future.
   Lang S, Schnabl B. · · 2020 · cited 194× · PMID 32791115 · DOI 10.1016/j.chom.2020.07.007
2. Dysregulation of serum bile acids and FGF19 in alcoholic hepatitis.
   Brandl K, Hartmann P, Jih LJ, Pizzo DP, et al · · 2018 · cited 172× · PMID 29654817 · DOI 10.1016/j.jhep.2018.03.031
3. Recent Advances in Understanding of Pathogenesis of Alcohol-Associated Liver Disease.
   Wu X, Fan X, Miyata T, Kim A, et al · · 2023 · cited 167× · PMID 36270295 · DOI 10.1146/annurev-pathmechdis-031521-030435
4. Update on FXR Biology: Promising Therapeutic Target?
   Han CY. · · 2018 · cited 133× · PMID 30013008 · DOI 10.3390/ijms19072069
5. Crosstalk between Oxidative Stress and Inflammatory Liver Injury in the Pathogenesis of Alcoholic Liver Disease.
   Yang YM, Cho YE, Hwang S. · · 2022 · cited 119× · PMID 35054960 · DOI 10.3390/ijms23020774
6. Nuclear bile acid signaling through the farnesoid X receptor.
   Mazuy C, Helleboid A, Staels B, Lefebvre P. · · 2015 · cited 85× · PMID 25511198 · DOI 10.1007/s00018-014-1805-y
7. Gut-liver axis signaling in portal hypertension.
   Simbrunner B, Mandorfer M, Trauner M, Reiberger T. · · 2019 · cited 82× · PMID 31660028 · DOI 10.3748/wjg.v25.i39.5897
8. The knowns and unknowns of treatment for alcoholic hepatitis.
   Sehrawat TS, Liu M, Shah VH. · · 2020 · cited 76× · PMID 32277902 · DOI 10.1016/s2468-1253(19)30326-7