ALK-001 for Stargardt Disease

(TEASE Trial)

Enrolling by invitation at 19 trial locations

Overseen By Leonide Saad, PhD

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Alkeus Pharmaceuticals, Inc.

Must not be taking: Vitamin A, Beta-carotene, Oral retinoids

Disqualifiers: Pregnancy, Liver disorder, Ocular disorder, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether the experimental drug ALK-001 (Gildeuretinol acetate) can safely slow Stargardt disease, a genetic eye condition that causes vision loss. Participants will take either ALK-001 or a placebo (a pill with no active drug) daily. The study is suitable for individuals aged 8 to 70 with Stargardt disease confirmed by genetic testing and specific eye conditions. Participants must not have recently used vitamin A supplements or have significant eye issues that could affect the study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important advancements in Stargardt disease treatment.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop all current medications, but you must not have taken supplements with vitamin A or beta-carotene, liver-based products, or prescription oral retinoid medications in the past 30 days.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have taken supplements with vitamin A, beta-carotene, liver-based products, or oral retinoid medications in the past 30 days.

Is there any evidence suggesting that ALK-001 is likely to be safe for humans?

Research shows that ALK-001, also known as gildeuretinol, is generally well-tolerated. Earlier studies found that patients with Stargardt disease who took ALK-001 for two to seven years did not experience worsening of their condition, suggesting the treatment did not cause major side effects.

While detailed information on specific side effects is not available, the long-term use in past studies provides some reassurance about its safety. The treatment is now in a mid-stage trial, indicating it has already demonstrated safety in earlier research phases. This trial aims to further assess how well patients tolerate the treatment over time. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Stargardt disease?

Unlike the standard treatments for Stargardt Disease, which mainly focus on managing symptoms, ALK-001 offers a unique approach by aiming to slow down the progression of the disease itself. ALK-001 is different because it introduces a modified form of vitamin A, which reduces the formation of toxic Vitamin A byproducts that contribute to retinal damage. This innovative mechanism of action targets the underlying cause of the disease, offering hope for more effective long-term management of Stargardt Disease. Researchers are excited about ALK-001’s potential to not just delay vision loss but also improve quality of life for patients.

What evidence suggests that ALK-001 might be an effective treatment for Stargardt disease?

Research has shown that ALK-001, also known as gildeuretinol, can help slow Stargardt disease, a genetic eye condition. In this trial, participants will receive either ALK-001 or a placebo. Studies have found that daily use of ALK-001 can significantly reduce the growth of damaged areas in the retina. Specifically, it can slow this growth by 21.6% compared to not taking the treatment. These findings suggest that ALK-001 could effectively manage Stargardt disease. ^{1 2 6 7 8}

Who Is on the Research Team?

Leonide Saad, PhD

Principal Investigator

Alkeus Pharmaceuticals, Inc.

Hendrik Scholl, MD

Principal Investigator

University of Basel

Are You a Good Fit for This Trial?

This trial is for individuals aged 8-70 with Stargardt disease, a genetic eye condition. Participants must have clear vision media and no allergies to eye dilation drops, be healthy overall, able to follow the study plan for two years, and females of childbearing age must agree to use contraception. Those with certain medical conditions or recent eye treatments are excluded.

Inclusion Criteria

I am between 8 and 70 years old and my ability to see is not limited.

I have been diagnosed with Stargardt disease.

I am aware of the birth defect risks and contraception requirements.

Exclusion Criteria

I have not taken vitamin A, beta-carotene supplements, liver products, or oral retinoids in the last 30 days.

I have a current or past liver condition.

Is lactating, pregnant, or has a positive serum or urine pregnancy test at screening or at randomization

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily oral administration of ALK-001 or placebo

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ALK-001

Trial Overview The trial tests ALK-001 (C20-D3-retinyl acetate) against a placebo to assess its safety over the long term and its impact on slowing down the progression of Stargardt disease. Patients will either receive ALK-001 or a placebo in this randomized study.

How Is the Trial Designed?

Group I: ALK-001 Experimental Treatment 1 Intervention

Daily, oral administration of one capsule. See details below.

Group II: Placebo Placebo Group 1 Intervention

Daily, oral administration of one capsule. See details below.

ALK-001 is already approved in United States for the following indications:

Approved in United States as Gildeuretinol for:

• Stargardt disease

Who Is Running the Clinical Trial?

Alkeus Pharmaceuticals, Inc.

Lead Sponsor

Trials

4

Recruited

520+

Published Research Related to This Trial

Isotretinoin effectively inhibited the accumulation of toxic lipofuscin pigments, specifically A2E, in a mouse model of recessive Stargardt's macular degeneration, suggesting a potential therapeutic strategy for this inherited blinding disease.

The treatment with isotretinoin did not result in significant visual loss in the treated mice, indicating its safety and potential efficacy in delaying visual decline associated with Stargardt's disease and possibly other retinal degenerations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isotretinoin treatment inhibits lipofuscin accumulation in a mouse model of recessive Stargardt's macular degeneration. Radu, RA., Mata, NL., Nusinowitz, S., et al.[2013]

The overlapping adeno-associated viral (AAV) dual vector system for delivering the ABCA4 gene showed no signs of toxicity in Abca4-/- mice, indicating it is safe for potential use in humans.

Both structural and functional assessments of the retina, including optical coherence tomography and electroretinography, confirmed that the dual vector system did not cause any adverse effects compared to sham injections, supporting its advancement to clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of AAV Dual Vector Safety in theAbca4-/- Mouse Model of Stargardt Disease. McClements, ME., Barnard, AR., Charbel Issa, P., et al.[2021]

In a study involving 23 subjects with Stargardt disease, emixustat demonstrated a dose-dependent effect on rod b-wave recovery rates, with the 10 mg dose showing near-complete suppression, indicating its potential efficacy in targeting RPE65.

The safety profile of emixustat was consistent with previous studies, primarily involving ocular adverse events, which suggests it may be a viable treatment option for Stargardt disease as it moves into a longer phase 3 trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomised study evaluating the pharmacodynamics of emixustat hydrochloride in subjects with macular atrophy secondary to Stargardt disease. Kubota, R., Birch, DG., Gregory, JK., et al.[2022]

Long-term treatment with deuterium-enriched vitamin A (C20-D(3)-vitamin A) in a mouse model of Stargardt disease showed potential to reduce lipofuscin accumulation in the retinal pigment epithelium, which is linked to vision loss.

The study suggests that preventing the formation of vitamin A dimers may slow down retinal damage and vision loss associated with Stargardt disease, indicating a possible new therapeutic approach for patients with ABCA4 genetic defects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

C20-D3-vitamin A slows lipofuscin accumulation and electrophysiological retinal degeneration in a mouse model of Stargardt disease. Ma, L., Kaufman, Y., Zhang, J., et al.[2021]

Genetic screening for Stargardt disease using a panel of 5 common ABCA4 mutations identified mutations in 50% of patients, while more comprehensive massive parallel sequencing confirmed a diagnosis in 84% of patients tested.

The majority of mutations found were in the ABCA4 gene, highlighting its significance in Stargardt disease, with specific mutations like p.L541P, p.A1038V, and p.G1961E being particularly prevalent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Molecular genetic diagnosis of Stargardt disease]. Sheremet, NL., Zhorzholadze, NV., Ronzina, IA., et al.[2019]

Stargardt disease, caused by mutations in the ABCA4 gene, currently lacks effective treatments that have successfully completed clinical trials.

Research is ongoing in various areas, including drugs to reduce harmful vitamin A dimers, stem cell therapies for retinal regeneration, and gene therapy aimed at delivering a functional ABCA4 gene directly into the eye.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New possibilities in the treatment of Stargardt disease]. Zhorzholadze, NV., Sheremet, NL., Tanas, AS., et al.[2020]

In a follow-up phase 1 trial involving 11 patients aged 11-46 years, the subretinal injection of AAV2-hRPE65v2 into the contralateral eye showed no serious adverse events related to the treatment, indicating a favorable safety profile.

Most patients experienced significant improvements in mobility and light sensitivity in the newly treated eye, with effects lasting up to 3 years, demonstrating the efficacy of AAV2-hRPE65v2 as a gene therapy for inherited retinal dystrophy caused by RPE65 mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and durability of effect of contralateral-eye administration of AAV2 gene therapy in patients with childhood-onset blindness caused by RPE65 mutations: a follow-on phase 1 trial. Bennett, J., Wellman, J., Marshall, KA., et al.[2022]

In a study involving 259 participants with Stargardt disease over 12 months, the progression rate of atrophic lesions was estimated at 0.76 mm² per year for definitely decreased autofluorescence, indicating a significant rate of disease progression.

Autofluorescence imaging was identified as a valuable tool for monitoring disease progression and could be used as an outcome measure in clinical trials aimed at slowing the progression of Stargardt disease, with progression rates influenced by the initial size of lesions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progression of Stargardt Disease as Determined by Fundus Autofluorescence Over a 12-Month Period: ProgStar Report No. 11. Strauss, RW., Kong, X., Ho, A., et al.[2022]

Stargardt disease (STGD) is caused by mutations in the ABCR gene, which is crucial for retinal function and is expressed primarily in rod photoreceptors.

The study identified 19 different mutations in the ABCR gene among STGD families, confirming its role as the causal gene for this autosomal recessive retinal disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A photoreceptor cell-specific ATP-binding transporter gene (ABCR) is mutated in recessive Stargardt macular dystrophy. Allikmets, R., Singh, N., Sun, H., et al.[2022]

There are currently eight ongoing clinical trials for Stargardt disease, focusing on various treatment strategies including gene therapy, neuroprotection, and stem cell therapy.

These trials aim to address the disease through different mechanisms, such as inhibiting toxic vitamin A dimers and restoring the function of the ABCA4 gene, which raises hope for effective treatments in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical Tests Testing New Therapies for Stargardt Disease]. Kousal, B., Ďuďáková, Ľ., Hlavatá, L., et al.[2019]

Isotretinoin effectively inhibited the accumulation of toxic lipofuscin pigments in a mouse model of recessive Stargardt's macular degeneration, suggesting it could delay visual loss in affected patients.

The treatment not only blocked the formation of A2E, a key component in lipofuscin biosynthesis, but also showed no significant visual loss in treated mice, indicating a potential safe therapeutic option for this inherited blinding disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment with isotretinoin inhibits lipofuscin accumulation in a mouse model of recessive Stargardt's macular degeneration. Radu, RA., Mata, NL., Nusinowitz, S., et al.[2018]

In a study of 217 patients with Stargardt disease, it was found that about 50% of eyes without definitely decreased autofluorescence (DDAF) at the first visit developed this lesion within 5 years, indicating that DDAF incidence could be a useful measure for evaluating treatment effectiveness.

The median time to develop DDAF lesions was 4.9 years, while for questionably decreased autofluorescence (QDAF) lesions it was 6.3 years, highlighting the progression of retinal damage in patients and the importance of monitoring these changes over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence of Atrophic Lesions in Stargardt Disease in the Progression of Atrophy Secondary to Stargardt Disease (ProgStar) Study: Report No. 5. Strauss, RW., Muñoz, B., Ho, A., et al.[2022]

Citations

1. alkeuspharma.com alkeuspharma.com/presentation-of-gildeuretinol-data-at-aao-2025/

October 9, 2025 Results from the study of oral gildeuretinol in moderate Stargardt disease to be presented as late-breaker during Retina Subspecialty Day.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02402660

Phase 2 Tolerability and Effects of ALK-001 on Stargardt ... This study evaluates the effects of orally-administered ALK-001 on the progression of Stargardt disease (ABCA4-related).

3. alkeuspharma.com alkeuspharma.com/alkeus-presents-gildeuretinol-data-during-arvo-2025-annual-meeting/

Alkeus Pharmaceuticals Presents Gildeuretinol Data ... The study showed daily oral gildeuretinol significantly slowed the growth of atrophic retinal lesions in Stargardt disease by a 21.6% reduction versus the ...

4. firstwordpharma.com firstwordpharma.com/story/5983376

Alkeus Pharmaceuticals Announces Gildeuretinol Data ... The Tolerability and Effects of ALK-001 on Stargardt diseasE (TEASE) studies consist of four independent clinical studies of oral gildeuretinol ...

5. ophthalmologytimes.com ophthalmologytimes.com/view/alkeus-pharmaceuticals-receives-fda-rare-pediatric-disease-and-fast-track-designations-for-gildeuretinol-as-treatment-for-stargardt-disease

Alkeus Pharmaceuticals receives FDA Rare Pediatric ... Gildeuretinol (ALK-001) received FDA Rare Pediatric Disease and Fast Track designations for Stargardt disease, highlighting its potential as a ...

6. firstwordpharma.com firstwordpharma.com/story/5987240

Alkeus Pharmaceuticals Announces Presentation of ... Early-stage Stargardt disease patients treated with gildeuretinol for two to seven years exhibited relatively stable disease over the course ...

7. biospace.com biospace.com/press-releases/alkeus-pharmaceuticals-announces-gildeuretinol-data-presentations-during-the-american-society-of-retina-specialists-asrs-43rd-annual-meeting-july-29-august-2

Alkeus Pharmaceuticals Announces Gildeuretinol Data ... The Tolerability and Effects of ALK-001 on Stargardt diseasE (TEASE) studies consist of four independent clinical studies of oral gildeuretinol ...

8. globenewswire.com globenewswire.com/news-release/2025/10/09/3164331/0/en/Alkeus-Pharmaceuticals-Announces-Presentation-of-Gildeuretinol-Data-at-the-American-Academy-of-Ophthalmology-AAO-2025-Annual-Meeting-October-18-21-in-Orlando.html

Alkeus Pharmaceuticals Announces Presentation of Results from the study of oral gildeuretinol in moderate Stargardt disease to be presented as late-breaker during Retina Subspecialty Day...