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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety and effectiveness of a new treatment, INT-787, for individuals with severe alcohol-related hepatitis, a serious liver condition often caused by heavy drinking. The trial aims to understand how different doses of the treatment work and how the body processes it. Participants will receive either the actual treatment or a placebo (a non-active lookalike). Suitable candidates for this trial have experienced severe alcohol-related hepatitis symptoms, such as jaundice (yellowing of the skin), particularly if these symptoms began within the last eight weeks and have a recent history of heavy alcohol use. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important medical advancements.

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.

Is there any evidence suggesting that INT-787 is likely to be safe for humans?

Research has shown that INT-787 is safe for humans. Early studies with healthy adults found that INT-787 was well-tolerated, with no serious side effects. In these studies, the body quickly absorbed INT-787, and its effects increased with higher doses, indicating that the treatment is manageable and predictable.

While these results are encouraging, they come from trials with healthy individuals, not those with severe alcohol-related liver disease. The current trial will examine the safety of INT-787 for people with this specific liver condition. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for alcoholic hepatitis, which typically includes corticosteroids and supportive care, INT-787 offers a novel approach. INT-787 is unique because it targets specific pathways involved in liver inflammation and regeneration, potentially leading to better outcomes. Researchers are excited about its potential to reduce liver damage more effectively and quickly than existing treatments, which could significantly improve recovery times and overall liver health.

What evidence suggests that INT-787 might be an effective treatment for severe alcoholic hepatitis?

Research suggests that INT-787, a new drug targeting specific liver receptors, might help treat severe alcohol-related hepatitis (sAH). In studies with mice, INT-787 improved liver function and caused beneficial genetic changes compared to obeticholic acid. Human trials have shown that INT-787 is generally well tolerated, with no serious side effects reported. In this trial, participants will receive either INT-787 or a placebo to confirm these results and determine the optimal dose for treatment. Overall, promising evidence indicates that INT-787 could help manage this liver condition. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

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.

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

I am following the required birth control guidelines.

Exclusion Criteria

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

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

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

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. interceptpharma.com interceptpharma.com/about-us/news/?id=2550372

Press Releases Results showed INT-787 was generally well tolerated in healthy subjects. No serious adverse events were reported. The majority of treatment-emergent adverse ...

2. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-effects-of-int-787-for-patients-with-severe-alcohol-associated-hepatitis/

Study on the Effects of INT-787 for Patients with Severe ... The purpose of the study is to evaluate how effective INT-787 is in managing the progression of this liver disease. Participants in the study ...

3. aasld.confex.com aasld.confex.com/aasld/2023/mediafile/Handout/Paper46822/%233503-C_Madison.pdf

A Phase 2a, Randomized, Double-Blind, Placebo- ... The novel FXR agonist INT-787 shows higher efficacy as well as greater hepatic and ileal gene modulation than obeticholic acid in the gubra-amln mouse model ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12559046/

Alcohol-Associated Hepatitis: Translating Pathophysiology ... A next-generation FXR agonist, INT-787, is currently under investigation in a Phase 2a clinical trial for the treatment of severe AH (FRESH ...

5. clinicaltrials.eu clinicaltrials.eu/inn/int-787/

Int-787 – Application in Therapy and Current Clinical ... The main purpose of this trial is to assess the safety, effectiveness, and optimal dosage of INT-787 in patients with severe alcohol-associated hepatitis (sAH).

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12042697/

Safety, Tolerability, Pharmacokinetics, and ... In conclusion, INT‐787 is a biologically active, well‐tolerated compound with rapid absorption and dose‐dependent exposure in healthy volunteers ...