Alcoholic HepatitisPhase 2TREATNCT02039219
Trial of Obeticholic Acid in Patients With Moderately Severe Alcoholic Hepatitis (AH)
A Phase 2 study testing 10 mg Obeticholic Acid (OCA) in people with Alcoholic Hepatitis, run by Naga P. Chalasani at 4 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Alcoholic Hepatitis
- What is being tested?
- 10 mg Obeticholic Acid (OCA)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 19 participants
- Where
- 4 sitesUnited States
- Study dates
- 3 Nov 2014to 29 Jan 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Indiana University
Indianapolis, Indiana, 46202
Einstein Healthcare Network
Philadelphia, Pennsylvania, 19141
Virgina Commonwealth University
Richmond, Virginia, 23298
Mayo Clinic
Rochester, Minnesota, 55905
About this study
Official title: 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.
- Conditions
- Alcoholic Hepatitis
- Being tested
- Placebo, 10 mg Obeticholic Acid (OCA)
- Medical subject headings
- Hepatitis, Alcoholic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
1 tablet of placebo, taken orally daily with water, approximately 30 minutes prior to breakfast for 6 weeks.
10 mg Obeticholic Acid (OCA)Drug
Also called INT-747
10 mg Obeticholic Acid (OCA) Study medication will be administered orally, once daily, approximately 30 minutes prior to breakfast for 6 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo Receives: Drug: Placebo |
| 10 mg Obeticholic Acid (OCA) | Experimental | 10 mg Obeticholic Acid (OCA) Study medication will be administered orally, once daily for 6 weeks. Receives: Drug: 10 mg Obeticholic Acid (OCA) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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).
Measured: 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.
Measured: Baseline to 6 weeks (Day 42)
Secondary outcomes (14)
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).
Measured: 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).
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
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.
Measured: Baseline to 180 days
Length of Hospital Stays
Measured: 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.
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.
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.
Measured: Baseline to 180 days
Discontinuation Rate During the Treatment and Follow-up Phases
Measured: Baseline to 180 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jan 2014 (estimated)
- Study start3 Nov 2014
- Primary completion30 Jul 2017
- Study completion29 Jan 2018
Why it stopped: Post-marketing reports of hepatotoxicity associated with obeticholic acid emerged in June 2017, investigators temporarily halted patient recruitment June 2017.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Alcoholic HepatitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Naga P. Chalasani
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA), Intercept Pharmaceuticals
- Responsible party
- Sponsor-investigator, Naga P. Chalasani, Indiana University
- Investigators
- Naga Chalasani, MD, Principal investigator, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02039219
- Sponsor's protocol ID
- TREAT 002
- Other IDs
- 1U01AA021840-01, U01AA021883, U01AA021891, U01AA021788
- Acronym
- TREAT
- Status last verified
- Jan 2020
- First submitted
- 15 Jan 2014
- Last updated
- 28 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-Blind, Placebo-Controlled Trial of Obeticholic Acid in Patients With Moderately Severe Alcoholic Hepatitis (AH)
- ClinicalTrials.gov ID
- NCT02039219
- Acronym / sponsor ID
- TREAT / TREAT 002
- Conditions
- Alcoholic Hepatitis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Post-marketing reports of hepatotoxicity associated with obeticholic acid emerged in June 2017, investigators temporarily halted patient recruitment June 2017.
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Naga P. ChalasaniUniversity, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA), Intercept Pharmaceuticals
- Study start
- 3 Nov 2014 (actual)
- Primary completion
- 30 Jul 2017 (actual)
- Study completion
- 29 Jan 2018 (actual)
- First posted
- 17 Jan 2014 (estimated)
- Results
- Posted 28 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboPlacebo |
| 10 mg Obeticholic Acid (OCA) | Experimental | Drug: 10 mg Obeticholic Acid (OCA)10 mg Obeticholic Acid (OCA) Study medication will be administered orally, once daily for 6 weeks. |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Placebo1 tablet of placebo, taken orally daily with water, approximately 30 minutes prior to breakfast for 6 weeks. | Drug | Placebo |
| 10 mg Obeticholic Acid (OCA)Also: INT-74710 mg Obeticholic Acid (OCA) Study medication will be administered orally, once daily, approximately 30 minutes prior to breakfast for 6 weeks. | Drug | 10 mg Obeticholic Acid (OCA) |
Primary outcome
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.
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).
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.
14 secondary outcomes
Any SAEs During the Follow-up Phase
Time frame: Days 42 to 180
SAEs Attributable to the Study Medicine During the Treatment and Follow-up Phases
Time frame: Baseline to 180 days
Adverse Events (AEs) During the Treatment and Follow-up Phases
Time frame: Baseline to 180 days
Change in MELD Score at 90 and 180 Days
Time frame: Days 90 and 180
Change in Child-Pugh Score at Day 42, 90 and 180 Days
Time frame: Days 42, 90 and 180
Percentage of Participants Deceased at Day 42, 90 and 180
Time frame: Days 42, 90 and 180
Rates of Hospitalization
Time frame: Baseline to 180 days
Changes in Intestinal Inflammation
Time frame: Baseline to Day 180
Changes in Serum Oxidative Stress.
Time frame: Baseline to 180 days
Length of Hospital Stays
Time frame: Baseline to 180 days
Changes in Bacterial Translocation
Time frame: Baseline to 180 days
Changes in Cytokines
Time frame: Baseline to 180 days
Changes in Activation of Innate Immunity
Time frame: Baseline to 180 days
Discontinuation Rate During the Treatment and Follow-up Phases
Time frame: Baseline to 180 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Naga Chalasani, MD principal investigator
Indiana University
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 10 mg Obeticholic Acid (OCA) in people with Alcoholic Hepatitis, run by Naga P. Chalasani at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
MELD Score Mean(SD) (time frame: Baseline to 6 weeks (Day 42)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jan 2020.