ACDN-01 for Stargardt Disease

(STELLAR Trial)

Recruiting at 9 trial locations

Overseen By Associate Director, Clinical Operations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Ascidian Therapeutics, Inc

Disqualifiers: Other retinal diseases, psychiatric conditions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

13 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is an open-label, single ascending dose clinical trial in participants who have ABCA4-related retinopathies. This is the first-in-human clinical trial in which ACDN-01 will be evaluated for safety, tolerability, and preliminary efficacy following a single subretinal injection of ACDN-01.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What safety data exists for ACDN-01 or similar treatments for Stargardt Disease?

Research on a similar treatment using adeno-associated viral (AAV) gene therapy in mice showed potential for adverse events, but it was a preliminary study before human trials. ^{1 2 3 4 5}

Research Team

Alia Rashid

Principal Investigator

Ascidian Therapeutics

Eligibility Criteria

The STELLAR study is for individuals with ABCA4-related retinopathies, which include conditions like Stargardt Disease and various forms of macular degeneration. Participants should have a diagnosis related to these eye diseases.

Inclusion Criteria

I have a mutation in the ABCA4 gene.

I have been diagnosed with Stargardt disease type 1 or cone-rod dystrophy.

I have thinning in the central part of my eye's retina.

Exclusion Criteria

I have genetic mutations linked to specific eye diseases.

I do not have ABCA4-related eye disease.

Presence of a medical condition (systemic or ophthalmic), psychiatric condition, including substance abuse disorder, or physical examination or laboratory finding that may in the opinion of the principal investigator and sponsor preclude adherence to the scheduled study visits, safe participation in the study, or affect the results of the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single subretinal injection of ACDN-01 at low, medium, or high dose levels

1 day

1 visit (in-person)

Primary Follow-up

Participants are monitored for safety and preliminary efficacy endpoints

24 months

Regular visits (in-person and virtual)

Long-term Follow-up

Participants continue to be monitored for long-term safety and efficacy

36 months

Periodic visits (in-person and virtual)

Treatment Details

Interventions

• ACDN-01

Trial Overview ACDN-01 is being tested in this trial. It's an experimental treatment given as a single subretinal injection to see if it's safe, tolerable, and potentially effective at treating the symptoms of ABCA4-related retinopathy.

Participant Groups

Group I: Mid-dose of ACDN-01 Experimental Treatment 1 Intervention

One time mid-dose of ACDN-01.

Group II: Low dose of ACDN-01 Experimental Treatment 1 Intervention

One time low dose of ACDN-01.

Group III: High dose of ACDN-01 Experimental Treatment 1 Intervention

One time high dose of ACDN-01.

ACDN-01 is already approved in United States for the following indications:

Approved in United States as ACDN-01 for:

• Stargardt disease
• ABCA4-related retinopathies

Who Is Running the Clinical Trial?

Ascidian Therapeutics, Inc

Lead Sponsor

Trials

2

Recruited

60+

Findings from Research

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]

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 of 200 patients with Stargardt disease type 1 (STGD1), microperimetry revealed a significant yearly decline in macular sensitivity, with an average decrease of -0.68 dB, indicating a measurable progression of the disease over approximately one year.

The increase in deep scotoma points by an average of 1.56 points per year suggests worsening visual function, highlighting the potential of microperimetry as a valuable tool for assessing treatment efficacy in clinical trials for STGD1.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Longitudinal Microperimetric Changes of Macular Sensitivity in Stargardt Disease After 12 Months: ProgStar Report No. 13. Schönbach, EM., Strauss, RW., Muñoz, B., et al.[2021]

Stargardt macular dystrophy (STGD1) is the most common inherited macular dystrophy caused by mutations in the ABCA4 gene, leading to significant advances in understanding its clinical and molecular features.

Current research is exploring various therapeutic interventions, including pharmacological treatments, cellular therapies, and innovative genetic therapies aimed at replacing the entire ABCA4 gene, which could potentially offer new hope for patients with STGD1.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stargardt macular dystrophy and therapeutic approaches. Fujinami, K., Waheed, N., Laich, Y., et al.[2023]

In a study of 12 patients with recessive Stargardt disease (STGD1), a distinct phenotype was observed characterized by advanced outer retinal degeneration, leading to a pale fundus appearance due to scleral exposure after approximately 50 years of disease progression.

The patients exhibited severe visual impairment, with best-corrected visual acuity ranging from 20/400 to hand motion, and significant loss of outer retinal structures was confirmed through imaging techniques, indicating a severe impact on retinal function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep Scleral Exposure: A Degenerative Outcome of End-Stage Stargardt Disease. Lee, W., Zernant, J., Nagasaki, T., et al.[2021]

References

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

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

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

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

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

Longitudinal Microperimetric Changes of Macular Sensitivity in Stargardt Disease After 12 Months: ProgStar Report No. 13. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Stargardt macular dystrophy and therapeutic approaches. [2023]

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

Deep Scleral Exposure: A Degenerative Outcome of End-Stage Stargardt Disease. [2021]