INT-787 for Alcoholic Hepatitis

(FRESH Trial)

Recruiting at 30 trial locations

Overseen By Thomas Capozza

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Intercept Pharmaceuticals

Must not be taking: Obeticholic acid, Corticosteroids

Disqualifiers: Pregnancy, Liver disease, HIV, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 4 weeks

80 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new drug called INT-787 for people with severe liver damage from heavy drinking. It aims to see if the drug is safe and effective, and how the body processes it. The goal is to find out if INT-787 can help improve liver health in these patients. Previous studies have shown that similar treatments can protect against liver injury.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot take products containing obeticholic acid or more than two doses of systemic corticosteroids within 30 days before starting the trial.

What makes the drug INT-787 unique for treating alcoholic hepatitis?

The drug INT-787 is unique for treating alcoholic hepatitis because it may target the gut microbiota, which is involved in the production of ethanol that contributes to liver disease. This approach is different from the standard use of corticosteroids, which focus on reducing inflammation rather than addressing the underlying microbial factors. ^{1 2 3 4 5}

Eligibility Criteria

Adults aged 18-65 with severe alcohol-associated hepatitis (sAH) can join this trial. They must have a history of heavy drinking, specific blood test results indicating liver inflammation, and agree to contraception or abstinence. Those unable to make decisions due to hepatic encephalopathy need consent from a legal representative.

Inclusion Criteria

I have been diagnosed with severe alcoholic hepatitis based on my alcohol use history and specific blood tests.

I am following the required birth control guidelines.

Participants must agree to participate in an alcohol use disorder program as recommended

Exclusion Criteria

I have not taken obeticholic acid or steroids in the last 30 days.

I have no history of serious gastrointestinal, kidney, liver, or gallbladder diseases.

Severe associated diseases, recent malignancy, positive urine drug screen, recent participation in other studies

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive INT-787 or placebo with dose escalation through cohorts

4 weeks

Weekly visits for dose escalation and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

Treatment Details

Interventions

• INT-787

Trial Overview The FRESH study is testing the safety and effectiveness of a drug called INT-787 in different doses for patients with sAH. It will also look at how the body processes the drug. Participants are monitored for their response to treatment and any changes in their condition.

Participant Groups

Group I: INT-787 Active Control 1 Intervention

Participants will be randomized to receive INT-787 (in Dose Escalation Cohorts \[Cohorts 1 through 4\] and Extension Phase Cohorts \[Cohorts 5 and 6\])

Group II: Placebo Placebo Group 2 Interventions

Participants will be randomized to receive matching placebo

Who Is Running the Clinical Trial?

Intercept Pharmaceuticals

Lead Sponsor

Trials

29

Recruited

16,600+

Findings from Research

In a study of 105 patients with severe alcoholic liver injury, those with severe alcoholic hepatitis (SAH) exhibited critical symptoms like severe hyperbilirubinemia and multiple organ failure, leading to a high mortality rate of 6.7%.

Prognostic factors for poor outcomes included elevated serum C-reactive protein (CRP) and the presence of disseminated intravascular coagulation (DIC), indicating that these factors can help predict the severity and prognosis of liver injury in chronic alcoholics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic factors in severe alcoholic liver injury. Nara Liver Study Group. Fujimoto, M., Uemura, M., Kojima, H., et al.[2019]

In a study of 146 individuals with nonalcoholic fatty liver disease (NAFLD), it was found that gut microbiota can produce significant amounts of ethanol, which increases with the severity of the disease, suggesting a potential role in disease progression.

The use of an alcohol dehydrogenase (ADH) inhibitor in a smaller group revealed that individuals with NAFLD had much higher ethanol levels in their blood after a meal, and this effect was eliminated with antibiotic treatment, indicating that specific gut bacteria may be responsible for this ethanol production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microbiome-derived ethanol in nonalcoholic fatty liver disease. Meijnikman, AS., Davids, M., Herrema, H., et al.[2022]

Germ-free mice experienced more severe liver injury and inflammation after binge-like alcohol exposure compared to conventional mice, suggesting that the intestinal microbiota plays a protective role against alcohol-induced liver damage.

The absence of microbiota in germ-free mice led to increased expression of alcohol-metabolizing enzymes, resulting in faster alcohol elimination from the blood, which indicates a complex interaction between gut bacteria and liver metabolism in response to alcohol.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microbiota Protects Mice Against Acute Alcohol-Induced Liver Injury. Chen, P., Miyamoto, Y., Mazagova, M., et al.[2018]

Corticosteroids are now considered the main treatment for alcoholic hepatitis, improving short-term survival rates, although they do not affect intermediate or long-term survival outcomes.

Prognosis for patients with alcoholic hepatitis can vary significantly, and refined scoring systems have improved the ability to predict outcomes and guide treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute Alcoholic Hepatitis. Im, GY.[2019]

In a study of 31 patients with alcoholic hepatitis, treatment with a broad-spectrum antibiotic did not significantly alter markers of bacterial translocation or systemic inflammation after 7 days, suggesting that bacterial translocation may be less critical once inflammation is established.

Despite the antibiotic treatment diversifying the gut bacteriome, there was no difference in 90-day mortality between the antibiotic group and the standard care group, indicating that this intervention did not improve survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

No Effect in Alcoholic Hepatitis of Gut-Selective, Broad-Spectrum Antibiotics on Bacterial Translocation or Hepatic and Systemic Inflammation. Støy, S., Laursen, TL., Eriksen, LL., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Prognostic factors in severe alcoholic liver injury. Nara Liver Study Group. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Microbiome-derived ethanol in nonalcoholic fatty liver disease. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Microbiota Protects Mice Against Acute Alcohol-Induced Liver Injury. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Acute Alcoholic Hepatitis. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

No Effect in Alcoholic Hepatitis of Gut-Selective, Broad-Spectrum Antibiotics on Bacterial Translocation or Hepatic and Systemic Inflammation. [2023]