ADX-629 Therapy for Sjogren-Larsson Syndrome

NCT05443685 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: 0517-22-FBSLS-ADX-629-001
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Sjogren-Larsson Syndrome

Keywords

ichthyosis; spasticity; intellectual disability; retinopathy; spastic diplegia

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0

  Participants are required to report any adverse events as they arise and will be contacted weekly for information regarding adverse events. Physical examinations with vital signs will be done monthly.

  weekly for 12 weeks

• Number of Participants With Abnormal Drug-related Safety Blood Tests

  Participants will have monthly medical tests to monitor safety of ADX-629 including complete blood count, comprehensive chemistry panel, vitamin A, vitamin B6 (pyridoxal phosphate), homocysteine, and urinalysis.

  monthly for 12 weeks

• Compliance and Tolerability of ADX-629

  A written drug log will be required for recording daily administration of ADX-629 tablets and any problems tolerating the drug. Unused tablets will be counted as a measure of compliance.

  daily for 12 weeks

Secondary Outcomes (1)

• Biochemical Efficacy of ADX-629 as Determined by Reversal of Abnormal Biomarkers

  Tests will be done at week 1 and week 12.

Other Outcomes (1)

• Exploratory Clinical Outcomes to Determine Drug Dependent Changes in Abnormal Clinical Measures

  Examinations and procedures will be done at week 1 and week 12.

Study Arms (1)

ADX-629 treatment

EXPERIMENTAL

Open label treatment with ADX-629

Drug: ADX-629

Interventions

ADX-629 DRUG

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.

Also known as: Open label

ADX-629 treatment

Eligibility Criteria

• Age: 5 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patricipant or participant's guardian is willing to provide written informed consent prior to the initiation of any study procedures. Assent will be solicited from participant intellectually capable of providing assent.
• Participant is willing to comply with all study procedures and availability for the duration of the study.
• Participant is 5-50 years of age at the time of enrollment.
• Participant has a genetically-confirmed diagnosis of SLS with two pathogenic sequence variants in ALDH3A2.
• Participant has active ichthyosis and neurologic symptoms of spasticity.
• Participant is able to swallow oral tablet medication and is willing to adhere to the study regimen.
• Participant is willing to suspend use of all topical creams 7 days before initial baseline evaluation and before the 12-week center visit.
• Participant has not been treated with any experimental drug for 1 month before baseline visit and during ADX-629 treatment.
• Participant who is sexually active agrees to use adequate contraception throughout the duration of the study, as follows:
• For females of child-bearing potential: Negative pregnancy test at Baseline and compliant with a medically approved contraceptive regimen during the study or documented to be surgically sterile or postmenopausal.
• For sexually-active men: Compliant with a barrier contraceptive regimen during the study.

You may not qualify if:

• History of any malignancy within 5 years of screening except for basal cell or squamous cell in situ skin carcinomas or carcinoma in situ of the cervix that has been treated with no evidence of recurrence.
• Participant is known to be human immunodeficiency virus (HIV) positive or has other known immunodeficiency.
• Participant has evidence of an active systemic or skin infection, including severe acute respiratory syndrome (SARS-CoV-2).
• History of significant tachycardia, bradycardia, acute or chronic cardiovascular disease, or any clinically significant abnormalities in rhythm or conduction detected on electrocardiogram (ECG), or QT interval corrected for heart rate using Fridericia's formula (QTcF) of \>440 ms or \<340 ms during screening.
• History or presence of gastrointestinal, hepatic disease, moderate or severe hepatic impairment (defined as Child-Pugh Class B and Class C) or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drug.
• Acute or chronic renal disease, moderate or severe renal impairment, history of renal disease, or estimated glomerular filtration rate (eGFR) \<60 mL/min/1.73 m2 calculated by Chronic Kidney Disease Epidemiology (CKD-EPI) equation.
• History of any other condition that, in the opinion of the Investigator, would compromise the participant's ability to comply with the protocol or that might compromise the participant's safety or the interpretation of the study results.
• Participant is currently receiving immunosuppressive therapy, including intermittent or low-dose corticosteroids and is not able or willing to suspend its use for a period from 2 weeks before and throughout the study.
• Participant is currently receiving and refuses to interrupt any systemic or topical medication that is excluded.
• Participant received an investigational systemic or topically administered prescription drug within 30 days before enrollment.
• Participant has received botulinum toxin (Botox) injections within 6 months of enrollment.
• Participant has a known allergic reaction to any ingredients of study drug formulation.
• Participant is currently participating in any other therapeutic clinical study.
• Participant is pregnant, intending to become pregnant, or breastfeeding.

Sponsors & Collaborators

• University of Nebraska: lead

Study Sites (1)

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Related Publications (3)

• Rizzo WB. Sjogren-Larsson syndrome: molecular genetics and biochemical pathogenesis of fatty aldehyde dehydrogenase deficiency. Mol Genet Metab. 2007 Jan;90(1):1-9. doi: 10.1016/j.ymgme.2006.08.006. Epub 2006 Sep 22.

  PMID: 16996289 BACKGROUND

• Rizzo WB. Genetics and prospective therapeutic targets for Sjogren-Larsson Syndrome. Expert Opin Orphan Drugs. 2016 Apr;4(4):395-406. doi: 10.1517/21678707.2016.1154453. Epub 2016 Mar 10.

  PMID: 27547594 BACKGROUND

• Rizzo WB, S'aulis D, Dorwart E, Bailey Z. Sjogren-Larsson syndrome: A biochemical rationale for using aldehyde-reactive therapeutic agents. Mol Genet Metab Rep. 2021 Dec 23;30:100839. doi: 10.1016/j.ymgmr.2021.100839. eCollection 2022 Mar.

  PMID: 35242571 BACKGROUND

MeSH Terms

Conditions

Sjogren-Larsson Syndrome; Ichthyosis; Muscle Spasticity; Intellectual Disability; Retinal Diseases; Cerebral Palsy

Interventions

ADX-629

Condition Hierarchy (Ancestors)

Skin Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipidoses; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Skin Diseases, Genetic; Infant, Newborn, Diseases; Keratosis; Skin Diseases; Skin and Connective Tissue Diseases; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Muscular Diseases; Musculoskeletal Diseases; Muscle Hypertonia; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurobehavioral Manifestations; Neurodevelopmental Disorders; Mental Disorders; Eye Diseases; Brain Damage, Chronic; Brain Diseases; Central Nervous System Diseases

Study Officials

• William B Rizzo, MD

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open label

Study Record Dates

• First Submitted: June 10, 2022
• First Posted: July 5, 2022
• Study Start: January 2, 2023
• Primary Completion: April 1, 2026
• Study Completion: April 1, 2026
• Last Updated: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)