ALK-001 for Stargardt Disease

(TEASE Trial)

Recruiting in Palo Alto (17 mi)

+5 other locations

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Alkeus Pharmaceuticals, Inc.

Prior Safety Data

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This trial tests a modified vitamin A pill called ALK-001 for people with Stargardt disease. The drug aims to prevent harmful clumps of vitamin A in the eye that cause vision loss.

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.

What data supports the idea that ALK-001 for Stargardt Disease is an effective treatment?

The available research does not provide specific data supporting the effectiveness of ALK-001 for Stargardt Disease. The studies mentioned focus on other treatments and the need for sensitive measures to track disease progression. There is no direct comparison or outcome data for ALK-001 in the provided information. ^{1 2 3 4 5}

What safety data exists for ALK-001 treatment in Stargardt Disease?

The research does not provide direct safety data for ALK-001 (Gildeuretinol, Gildeuretinol acetate, C20-D3-retinyl acetate) in Stargardt Disease. However, a study on C20-D3-vitamin A, which is related to ALK-001, suggests it may slow lipofuscin accumulation and retinal degeneration in a mouse model of Stargardt Disease, indicating potential safety and efficacy. No adverse effects are mentioned in the study, but specific safety data for ALK-001 in humans is not provided in the available research. ^{6 7 8 9 10}

Is the drug ALK-001 a promising treatment for Stargardt Disease?

Yes, ALK-001 is a promising drug for Stargardt Disease because it aims to address the underlying issues of the disease, such as reducing harmful substances in the eye that contribute to vision loss. ^{1 2 3 11 12}

Research Team

Leonide Saad, PhD

Principal Investigator

Alkeus Pharmaceuticals, Inc.

Hendrik Scholl, MD

Principal Investigator

University of Basel

Eligibility Criteria

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.

Healthy as judged by investigator

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

Treatment Details

Interventions

• ALK-001 (Vitamin A Derivative)

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.

Participant Groups

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.

Who Is Running the Clinical Trial?

Alkeus Pharmaceuticals, Inc.

Lead Sponsor

Trials

4

Recruited

520+

Findings from Research

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 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]

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 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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Randomised study evaluating the pharmacodynamics of emixustat hydrochloride in subjects with macular atrophy secondary to Stargardt disease. [2022]

2. Czech Republic pubmed.ncbi.nlm.nih.gov

[Clinical Tests Testing New Therapies for Stargardt Disease]. [2019]

3. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[New possibilities in the treatment of Stargardt disease]. [2020]

4. United States 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. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Progression of Stargardt Disease as Determined by Fundus Autofluorescence Over a 12-Month Period: ProgStar Report No. 11. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Isotretinoin treatment inhibits lipofuscin accumulation in a mouse model of recessive Stargardt's macular degeneration. [2013]

7. United States pubmed.ncbi.nlm.nih.gov

Assessment of AAV Dual Vector Safety in theAbca4-/- Mouse Model of Stargardt Disease. [2021]

8. England 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. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

C20-D3-vitamin A slows lipofuscin accumulation and electrophysiological retinal degeneration in a mouse model of Stargardt disease. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Treatment with isotretinoin inhibits lipofuscin accumulation in a mouse model of recessive Stargardt's macular degeneration. [2018]

11. United States pubmed.ncbi.nlm.nih.gov

A photoreceptor cell-specific ATP-binding transporter gene (ABCR) is mutated in recessive Stargardt macular dystrophy. [2022]

12. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Molecular genetic diagnosis of Stargardt disease]. [2019]