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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety and effectiveness of a drug called ADX-629 for individuals with moderate alcoholic hepatitis, a liver condition caused by heavy drinking. Researchers are testing ADX-629 in two different doses to determine which is most effective. Individuals diagnosed with alcoholic hepatitis, who have agreed to stop drinking, and can take pills might be suitable for this trial. Participants must commit to remaining alcohol-free and adhering to the study guidelines. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, providing participants an opportunity to contribute to significant medical advancements.

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.

Is there any evidence suggesting that ADX-629 is likely to be safe for humans?

Research has shown that ADX-629 was generally well-tolerated in past studies. These trials reported no serious side effects, and importantly, no side effects were directly linked to ADX-629. This suggests the treatment is likely safe. The studies aimed to reduce liver problems such as inflammation and high fat levels. These results are encouraging for those considering joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for alcoholic hepatitis, which mainly focus on managing symptoms and inflammation, ADX-629 offers a novel approach by targeting and modulating the body's immune response. Researchers are excited because ADX-629 is designed to address the underlying immune dysregulation associated with the condition, potentially leading to more effective and quicker recovery. This innovative mechanism could provide a significant advantage over traditional options like corticosteroids and pentoxifylline, which often have limited effectiveness and come with a range of side effects.

What evidence suggests that ADX-629 might be an effective treatment for alcoholic hepatitis?

Research has shown that ADX-629 holds promise for improving liver function in individuals with alcohol-related hepatitis. In this trial, participants will receive either 125 mg or 250 mg of ADX-629 twice daily. One study found significant improvements in liver health markers, such as the MELD score, which measures liver disease severity. The results were statistically strong, indicating they are unlikely due to chance. Additionally, notable reductions in triglyceride levels and C-Reactive Protein (CRP) were observed, both important for liver health. These findings suggest that ADX-629 could effectively treat moderate alcohol-related hepatitis. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. ir.aldeyra.com ir.aldeyra.com/news-releases/news-release-details/aldeyra-therapeutics-announces-positive-results-phase-2-clinical

Press Release Details Relative to Baseline, Signal-Finding Molecule ADX‑629 Demonstrated Statistically Significant Improvement in Liver Function in Patients with ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06685692

NCT06685692 | A Clinical Trial Investigating the Safety ... A Phase 2 Clinical Trial Investigating the Safety and Efficacy of ADX-629 in Subjects with Moderate Alcohol Associated Hepatitis (Part 1)

3. clinicaltrialsarena.com clinicaltrialsarena.com/news/aldeyra-reshuffles-pipeline-culling-asset-despite-phase-ii-success/

Aldeyra reshuffles pipeline, culling asset despite Phase II ... The biotech announced the Phase II data showing that ADX-629, a signal-finding RASP modulator, significantly improved markers of hepatic ...

4. taurigo.com taurigo.com/stocks/ALDX/articles/aldyera-adx629-phase2-trial-results-alcohol-hepatitis

Aldeyra's ADX-629 Shows Promise for Alcohol Hepatitis The trial's outcomes suggest a promising safety profile and a strategic focus on next-generation therapies.

5. clival.com clival.com/news/aldeyra-therapeutics-reports-positive-liver-function-results-for-adx-629-refocuses-pipeline-on-next-generation-rasp-modulators

Refocuses Pipeline on Next-Generation RASP Modulators Phase 2 Results for ADX-629 · Model for End-Stage Liver Disease (MELD) score: P=0.001 · Triglyceride levels: P<0.0001 · C-Reactive Protein (CRP) ...

6. ir.aldeyra.com ir.aldeyra.com/news-releases/news-release-details/aldeyra-therapeutics-provides-clinical-and-regulatory-update-and

Aldeyra Therapeutics Provides Clinical and Regulatory ... In preclinical models of ethanol toxicity, ADX-629 decreased hepatic levels of RASP, triglycerides, and inflammatory cytokines. In a sequence- ...

7. withpower.com withpower.com/trial/phase-2-hepatitis-a-10-2024-04bb0

ADX-629 for Alcoholic Hepatitis This Phase 2 medical study run by Aldeyra Therapeutics, Inc. is evaluating whether ADX-629 will have tolerable side effects & efficacy for patients with ...

8. morningstar.com morningstar.com/news/business-wire/20251028764760/aldeyra-therapeutics-announces-positive-results-from-phase-2-clinical-trial-in-alcohol-associated-hepatitis-focuses-rasp-product-candidate-pipeline-on-next-generation-molecules

Aldeyra Therapeutics Announces Positive Results from ... No serious adverse events were reported, and no adverse events were deemed related to ADX-629. “Consistent with clinical trials in patients with ...