ADX-629 for Alcoholic Hepatitis

Recruiting at 5 trial locations

Overseen By Bill Cavanagh Clinical Operations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Aldeyra Therapeutics, Inc.

Disqualifiers: Pregnancy, Recent trial enrollment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

10 Participants Needed

Trial Summary

What is the purpose of this trial?

A Phase 2 Clinical Trial Investigating the Safety and Efficacy of ADX-629 in Subjects with Moderate Alcohol Associated Hepatitis (Part 1)

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators for more details.

How is the drug ADX-629 different from other drugs for alcoholic hepatitis?

There is no widely accepted, effective treatment for alcoholic hepatitis, and existing options like prednisolone and pentoxifylline have limitations and risks. ADX-629 may offer a novel approach, potentially targeting different pathways or mechanisms, but specific details about its uniqueness compared to other treatments are not provided in the available research. ^{1 2 3 4 5}

Eligibility Criteria

This clinical trial is for individuals with alcoholic hepatitis, a condition where the liver is inflamed due to excessive alcohol intake. Specific details about who can join are not provided, but typically participants must meet certain health standards and may need to have a particular severity of disease.

Inclusion Criteria

I have been diagnosed with alcoholic hepatitis.

I am 21 years old or older.

Agreement to abstain from alcohol and utilize resources to cease at-risk behaviors during the trial, including addiction/alcohol abuse treatment

Exclusion Criteria

Pregnant, intending to become pregnant (or father a child), or breastfeeding

Current or recent enrollment in another interventional trial in the 30 days prior to screening

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ADX-629 at either 125 mg or 250 mg twice daily

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• ADX-629

Trial Overview The trial is testing ADX-629, which is likely a new treatment or medication. The study aims to determine how safe it is for patients and how effective it might be in treating alcoholic hepatitis. This part of the trial (Part 1) suggests there may be multiple phases.

Participant Groups

Group I: ADX-629 (250 mg twice daily) Experimental Treatment 1 Intervention

Group II: ADX-629 (125 mg twice daily) Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Aldeyra Therapeutics, Inc.

Lead Sponsor

Trials

34

Recruited

4,700+

Findings from Research

Pentoxifylline may reduce overall mortality in patients with alcoholic hepatitis, showing a risk ratio of 0.64 compared to control, but this finding is uncertain due to high risk of bias in most studies and lack of support from trial sequential analysis.

While pentoxifylline appears to lower mortality related to hepatorenal syndrome, it may also increase the occurrence of serious and non-serious adverse events, indicating that its safety and efficacy remain unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pentoxifylline for alcoholic hepatitis. Whitfield, K., Rambaldi, A., Wetterslev, J., et al.[2023]

Alcoholic hepatitis is a serious liver disease with a high short-term mortality rate of 25%-35%, characterized by specific histopathological features such as neutrophil infiltration and Mallory hyaline bodies.

For severe cases of alcoholic hepatitis, corticosteroids (like prednisolone) are recommended over pentoxifylline, as they have shown greater efficacy despite a higher risk of complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in alcoholic liver disease: An update on alcoholic hepatitis. Liang, R., Liu, A., Perumpail, RB., et al.[2018]

In a study using mice with alcoholic liver disease (ALD), the LXR inverse agonist SR9238 significantly reduced liver injury and nearly eliminated fibrosis after 4 weeks of treatment, indicating its potential as a protective therapy.

SR9238 effectively reversed the damage caused by chronic alcohol consumption, restoring liver morphology to near normal, suggesting that targeting LXR activity could be a promising approach for treating ALD in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of Hepatotoxicity by a LXR Inverse Agonist in a Model of Alcoholic Liver Disease. Sengupta, M., Griffett, K., Flaveny, CA., et al.[2020]

In a clinical trial involving 135 patients with severe alcoholic hepatitis, the addition of metadoxine (MTD) to standard treatments significantly improved survival rates at both 3 months (68.6% vs 20% for prednisone alone) and 6 months (48.6% vs 20% for prednisone alone).

Patients receiving MTD were more likely to maintain alcohol abstinence (74.5% vs 59.4%), which was identified as a crucial factor for improving survival outcomes in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metadoxine improves the three- and six-month survival rates in patients with severe alcoholic hepatitis. Higuera-de la Tijera, F., Servín-Caamaño, AI., Serralde-Zúñiga, AE., et al.[2022]

A single moderate dose of ethanol (20 g) significantly increased intestinal permeability in 12 healthy volunteers, indicating that even moderate alcohol consumption can disrupt gut barrier integrity.

The study identified the MAPK signaling pathway as a key mechanism in this disruption, with ethanol causing changes in tight junction proteins and increased expression of myosin light chain kinase, which could be reversed by specific inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ethanol impairs intestinal barrier function in humans through mitogen activated protein kinase signaling: a combined in vivo and in vitro approach. Elamin, E., Masclee, A., Troost, F., et al.[2022]

References

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

Pentoxifylline for alcoholic hepatitis. [2023]

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

Advances in alcoholic liver disease: An update on alcoholic hepatitis. [2018]

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

Inhibition of Hepatotoxicity by a LXR Inverse Agonist in a Model of Alcoholic Liver Disease. [2020]

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

Metadoxine improves the three- and six-month survival rates in patients with severe alcoholic hepatitis. [2022]

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

Ethanol impairs intestinal barrier function in humans through mitogen activated protein kinase signaling: a combined in vivo and in vitro approach. [2022]