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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
8
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.
University of Nebraska Medical Center
Omaha, Nebraska, United States
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.
Time frame: 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.
Time frame: 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.
Time frame: daily for 12 weeks
Biochemical Efficacy of ADX-629 as Determined by Reversal of Abnormal Biomarkers
Biochemical efficacy of ADX-629 in reversing disease-specific abnormalities in blood levels of fatty alcohols, alkylglycerol lipids, SLS metabolomic profile, SLS lipid profile, and oxidative stress markers. Skin elasticity and thickness, transepidermal water loss, stratum corneum fatty alcohols and alkylglycerol lipids will also be measured.
Time frame: Tests will be done at week 1 and week 12.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.