NCT05443685

ADX-629 Therapy for Sjogren-Larsson Syndrome

An Open-Label, Phase 1/2, Single-Site Study of the Safety, Biochemical Efficacy, and Exploratory Clinical Effects of Oral ADX-629 in Subjects With Sjögren-Larsson Syndrome

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 8 (actual)
• Sponsor: University of Nebraska · Academic / Other
• Sex: All
• Age: 5 Years – 50 Years
• Healthy volunteers: Not accepted

Summary

This research study will determine whether orally administered ADX-629 is safe and has biochemical efficacy in participants with Sjögren-Larsson syndrome (SLS), a rare inherited disorder of fatty aldehyde metabolism The disease is caused by bi-allelic mutations in ALDH3A2, which results in deficient activity of fatty aldehyde dehydrogenase (FALDH) and leads to the build-up of harmful long-chain (C16-C20) aldehydes and alcohols. Accumulation of these lipids and their metabolic products in skin, brain and eyes is responsible for the symptoms, which persist lifelong. ADX-629 is an aldehyde trapping agent that is expected to eliminate fatty aldehydes and negate aldehyde toxicity, improve the biochemical abnormalities and have clinical efficacy for SLS. The primary objective of this clinical protocol is to determine whether ADX-629 is safe and tolerable for use in SLS subjects. The secondary objective is to determine the efficacy of ADX-629 in reversing the biochemical abnormalities in SLS. Exploratory objectives are to evaluate the short-term clinical effects of ADX-629 on neurologic, cutaneous and ophthalmologic disease in SLS. Participants will be treated with ADX-629 for 12 weeks and monitored for safety and biochemical efficacy.

Detailed description

Sjögren-Larsson syndrome (SLS) is a rare inherited disorder of fatty aldehyde metabolism characterized by congenital ichthyosis, spastic diplegia, intellectual disability, seizures and a distinctive retinopathy. The disease is caused by bi-allelic mutations in ALDH3A2, which results in deficient activity of fatty aldehyde dehydrogenase (FALDH) and leads to the build-up of harmful long-chain (C16-C20) aldehydes and alcohols. Accumulation of these lipids and their metabolic products in skin, brain and eyes is responsible for the symptoms, which persist lifelong. Investigators hypothesize that elimination of fatty aldehydes using the oral pharmacologic aldehyde trapping agent ADX-629 will negate aldehyde toxicity, improve the biochemical abnormalities and have clinical efficacy for SLS patients. This study is an open label, Phase 1/2, single center investigation of ADX-629 in SLS. The primary objective is to determine whether ADX-629 is safe and tolerable for use in SLS participants. The secondary objective is to determine the efficacy of ADX-629 in reversing the biochemical abnormalities in SLS. Exploratory objectives are to evaluate the short-term clinical effects of ADX-629 on neurologic, cutaneous and ophthalmologic disease in SLS. Up to 10 paticipants with genetically confirmed SLS who meet eligibility criteria will be enrolled. All participantss will be studied at the University of Nebraska Medical Center/Children's Hospital \& Medical Center in Omaha, Nebraska. Participants will be treated with ADX-629 administered orally as 250 mg tablets for 12 weeks. Participants will be monitored for safety of ADX-629 every 4 weeks by physical examination and biochemical safety tests. The effects of ADX-629 on SLS-specific biomarkers will be determined after 12 weeks of drug treatment. Clinical tests will monitor neurological, dermatological and ophthalmologic response to drug.

Conditions

• Sjogren-Larsson Syndrome

Interventions

Type	Name	Description
DRUG	ADX-629	Particpants 10-50 years old will be administered ADX-629 250 mg tablets twice daily. Participants 5-9 years old will be administered ADX-629 125 mg tablets twice daily.

Timeline

• Start date: 2023-01-02
• Primary completion: 2026-09-01
• Completion: 2027-03-01
• First posted: 2022-07-05
• Last updated: 2026-02-10

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study