Sjogren-Larsson SyndromePhase 1/2NCT05443685
ADX-629 Therapy for Sjogren-Larsson Syndrome
A Phase 1/2 study testing ADX-629 in people with Sjogren-Larsson Syndrome, run by University of Nebraska at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 5 to 50 years
- Conditions the study is for
- Sjogren-Larsson Syndrome
- What is being tested?
- ADX-629
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Jan 2023to 1 Apr 2026
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 50 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Show all 11Show fewer
- 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.
Who cannot join
- 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.
Show all 14Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Nebraska Medical Center
Omaha, Nebraska, 68198
About this study
Official title: 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
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.
Read the 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
- Being tested
- ADX-629
- Keywords
- ichthyosis, spasticity, intellectual disability, retinopathy, spastic diplegia
- Medical subject headings
- Sjogren-Larsson Syndrome, Ichthyosis, Muscle Spasticity, Intellectual Disability, Retinal Diseases, Cerebral Palsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ADX-629Drug
Also called Open label
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.
| Study group | Role | What they receive |
|---|---|---|
| ADX-629 treatment | Experimental | Open label treatment with ADX-629 Receives: Drug: ADX-629 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: daily for 12 weeks
Secondary outcomes (1)
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.
Measured: Tests will be done at week 1 and week 12.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jul 2022
- Study start2 Jan 2023
- Primary completion1 Apr 2026
- Study completion1 Apr 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Sjogren-Larsson SyndromeStudies of the same condition, open and under way.
- More trials run by University of NebraskaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Open label
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Nebraska
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- William B Rizzo, MD, Principal investigator, University of Nebraska
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05443685
- Sponsor's protocol ID
- 0517-22-FB
- Other IDs
- SLS-ADX-629-001
- Status last verified
- Apr 2026
- First submitted
- 10 Jun 2022
- Last updated
- 5 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Aggregate de-identified data will be shared with other investigators by request.
Publications
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.
PubMed 16996289Rizzo 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.
PubMed 27547594Rizzo 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.
PubMed 35242571
Study at a glance
From the registry record, last updated by the sponsor on 5 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05443685
- Acronym / sponsor ID
- 0517-22-FB
- Conditions
- Sjogren-Larsson Syndrome
- Keywords
- ichthyosis, spasticity, intellectual disability, retinopathy, spastic diplegia
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- University of NebraskaUniversity, hospital or other
- Study start
- 2 Jan 2023 (actual)
- Primary completion
- 1 Apr 2026 (actual)
- Study completion
- 1 Apr 2026 (actual)
- First posted
- 5 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Open label
| Arm | Type | Receives |
|---|---|---|
| ADX-629 treatment | Experimental | Drug: ADX-629Open label treatment with ADX-629 |
Who may qualify
- Ages
- 5 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ADX-629Also: Open labelParticpants 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. | Drug | ADX-629 treatment |
Primary outcome
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0
Time frame: weekly for 12 weeks
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.
Number of Participants With Abnormal Drug-related Safety Blood Tests
Time frame: monthly for 12 weeks
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.
Compliance and Tolerability of ADX-629
Time frame: daily for 12 weeks
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.
1 secondary outcome
Biochemical Efficacy of ADX-629 as Determined by Reversal of Abnormal Biomarkers
Time frame: Tests will be done at week 1 and week 12.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 May 2026.
- Background: PubMed 16996289Rizzo 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.
- Background: PubMed 27547594Rizzo 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.
- Background: PubMed 35242571Rizzo 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.
- Individual participant dataSharing planned: No. Aggregate de-identified data will be shared with other investigators by request.
Related trials for Sjogren-Larsson Syndrome
RecruitingObservational study
The Myelin Disorders Biorepository Project
Leukodystrophy, White Matter Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
William B Rizzo, MD principal investigator
University of Nebraska
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ADX-629 in people with Sjogren-Larsson Syndrome, run by University of Nebraska at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 (time frame: weekly for 12 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05443685, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 May 2026.