SB-007 for Stargardt Disease

(ASTRA Trial)

Recruiting at 4 trial locations

Overseen By SpliceBio

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Splice Bio

Must not be taking: Vitamin A, Retinoids

Disqualifiers: Intraocular surgery, Amblyopia, others

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

Compensation: Varies

Number of Visits: 97

Duration: 1 day

57 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires participants to stop taking supplements containing vitamin A or beta-carotene, liver-based products, and prescription oral retinoids. However, topical products containing vitamin A or retinoids are allowed.

How is the drug SB-007 different from other treatments for Stargardt Disease?

SB-007 is unique because it is being tested specifically for Stargardt Disease, a condition that currently lacks effective treatment options. While other therapies like gene therapy and stem cell therapy are being explored, SB-007 may offer a novel approach, potentially involving a new mechanism of action or administration method not yet available in existing treatments. ^{1 2 3 4 5}

What is the purpose of this trial?

This Phase 1/2 study will evaluate the safety, tolerability, and preliminary efficacy of subretinal SB-007 administration to determine dose selection in subjects with Stargardt's Type 1 (STGD1). This is a multicenter study which will enroll approximately 57 subjects, followed up over a 96 week period post treatment after a single administration of SB-007.

Eligibility Criteria

This trial is for individuals with Stargardt Disease (STGD1), a type of inherited eye disorder that affects vision. Participants should be diagnosed with STGD1 and meet other study requirements set by the researchers.

Inclusion Criteria

Provide written consent. Subjects under legal age will also provide informed assent according to guidelines

Understand and comply with the study procedures

For women of child-bearing potential (WOCBP), have a negative pregnancy test at Screening and, if due to receive active treatment, at Day 0

Exclusion Criteria

Unwilling to stop taking specified products at Screening and throughout the study

Received investigational therapy within 90 days of the Screening Visit or 5 half-lives, whichever is longer

Known serious allergies to specified substances

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single subretinal injection of SB-007 at varying doses to evaluate safety and preliminary efficacy

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

96 weeks

Regular visits over 96 weeks

Treatment Details

Interventions

• SB-007

Trial Overview The trial is testing SB-007, which is given as a subretinal injection to see if it's safe and can help improve vision in people with Stargardt Disease. The study will involve about 57 subjects who will be monitored for up to 96 weeks after treatment.

Participant Groups

Group I: Phase 2 Dose Expansion: Dose 2 from Phase 1 Randomised Arm Experimental Treatment 1 Intervention

Subjects will receive a subretinal injection of SB-007 with lower dose than Maximum tolerated dose (MTD) from Phase 1

Group II: Phase 2 Dose Expansion: Dose 1 from Phase 1 Randomised Arm Experimental Treatment 1 Intervention

Subjects will receive a subretinal injection of SB-007 with Maximum tolerated dose (MTD) from Phase 1

Group III: Phase 1 Dose Escalation - Medium Dose Experimental Treatment 1 Intervention

Medium Dose: Subjects will receive subretinal injection of SB-007 in the medium dose group

Group IV: Phase 1 Dose Escalation - Low Dose Experimental Treatment 1 Intervention

Low Dose: Subjects will receive subretinal injection of SB-007 in the low dose group

Group V: Phase 1 Dose Escalation - High Dose Experimental Treatment 1 Intervention

High Dose: Subjects will receive subretinal injection of SB-007 in the high dose group

Group VI: Phase 2 No Intervention - Randomised Control Arm Active Control 1 Intervention

No Intervention Control Arm: Subject will not receive any active study intervention

Who Is Running the Clinical Trial?

Splice Bio

Lead Sponsor

Trials

1

Recruited

80+

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 incidence of Stargardt disease (STGD1) was found to be between 1.67 and 1.95 cases per million per year, with a point prevalence of approximately 1 in 22,000 people in 2018, indicating it is a relatively rare condition.

Late-onset STGD1 (diagnosed at age 45 or older) has increased in recent years, making up 33% of diagnoses from 2014-2018, likely due to improved awareness, but misdiagnosis as age-related macular degeneration was common in this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stargardt disease: monitoring incidence and diagnostic trends in the Netherlands using a nationwide disease registry. Runhart, EH., Dhooge, P., Meester-Smoor, M., 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]

Investigational therapies for Stargardt macular dystrophy (STGD1), including gene therapy and complement inhibitors, show promise in animal models but lack proven efficacy in human trials, highlighting the need for further research.

Visual cycle modulators (VCMs) like fenretinide and emixustat have not successfully improved vision in trials for age-related macular degeneration (AMD) and STGD1, indicating that while they are biologically plausible, their effectiveness remains uncertain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stargardt macular dystrophy and evolving therapies. Hussain, RM., Ciulla, TA., Berrocal, AM., et al.[2019]

References

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

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

2. England pubmed.ncbi.nlm.nih.gov

Stargardt disease: monitoring incidence and diagnostic trends in the Netherlands using a nationwide disease registry. [2022]

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

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

4. Germany pubmed.ncbi.nlm.nih.gov

The absence of fundus abnormalities in Stargardt disease. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Stargardt macular dystrophy and evolving therapies. [2019]