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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new treatment called SB-007 for Stargardt Disease, a genetic eye condition that causes vision loss. Researchers seek to determine if SB-007 is safe and effective when injected under the retina. The study will involve different groups receiving various doses to identify the optimal one. Individuals with Stargardt Type 1, confirmed by genetic testing and exhibiting symptoms like vision loss, might be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that this trial's treatment is likely to be safe?

Research has shown that SB-007 is a new treatment for Stargardt Disease. This gene therapy targets the root cause of the eye condition. Although still in early testing stages, the FDA has approved it for clinical trials, suggesting potential safety. In these trials, SB-007 is administered through an injection under the retina.

The main goal is to assess how well participants tolerate SB-007. The trials are carefully designed to determine the right dose by testing different amounts and observing reactions. Prospective participants should know that the trials aim to make the treatment as safe and effective as possible. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for Stargardt Disease, which typically involves supportive measures such as vitamin A restriction, use of sunglasses, or low vision aids, SB-007 offers a novel approach. Researchers are excited about SB-007 because it involves a subretinal injection that directly targets the retinal cells affected by the disease, potentially altering the course of the condition. This treatment aims to deliver a therapeutic dose directly to the site of degeneration, which could lead to more effective outcomes compared to current management strategies that primarily focus on symptom control rather than halting disease progression.

What evidence suggests that SB-007 might be an effective treatment for Stargardt Disease?

Research has shown that SB-007 is a promising treatment for Stargardt disease, an eye condition. This treatment targets the main cause of the disease, involving changes in the ABCA4 gene. Early results suggest that SB-007 can improve the retina's structure over 24 months, which is important for protecting vision in people with Stargardt disease. In this trial, participants will receive different doses of SB-007 to evaluate its effectiveness across various ABCA4 gene changes. These encouraging findings make SB-007 an exciting option in the fight against this eye condition. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06942572

Study Details | NCT06942572 | A Phase 1/2, First-in ... This Phase 1/2 study will evaluate the safety, tolerability, and preliminary efficacy of subretinal SB-007 administration to determine dose selection in ...

2. retinalphysician.com retinalphysician.com/issues/2025/october/novel-therapies-for-stargardt-disease/

Novel Therapies for Stargardt Disease Building on this, 24-months phase 2 data reported favorable structural outcomes. ... efficacy of SB-007 in STGD.23. Modifier Gene Therapy Approach.

3. fightingblindness.org fightingblindness.org/news/stargardt-disease-research-advances-862

Stargardt Disease Research Advances A Phase 1/2 clinical trial for SB-007, its emerging protein splicing therapy for Stargardt disease caused by ABCA4 mutations.

4. prnewswire.com prnewswire.com/news-releases/splicebio-announces-first-patient-dosed-in-phase-12-astra-study-of-sb-007-a-dual-aav-gene-therapy-for-stargardt-disease-302400963.html

SpliceBio Announces First Patient Dosed in Phase 1/2 ... A single dose of SB-007 has the potential to address the root cause of Stargardt disease across all ABCA4 mutations. The Phase 1/2 ASTRA study ...

5. clinicaltrials.eu clinicaltrials.eu/trial/evaluation-of-sb-007-safety-and-efficacy-in-patients-with-stargardt-disease-type-1-stgd1-caused-by-abca4-gene-mutations/

Evaluation of SB-007 Safety and Efficacy in Patients with ... The study will test a medication called SB-007, which is administered through a subretinal injection (an injection under the retina of the eye).

6. europe.ophthalmologytimes.com europe.ophthalmologytimes.com/view/first-patient-dosed-in-phase-1-2-astra-study-for-stargardt-disease-therapy-sb-007-splicebio-

First patient dosed in Phase 1/2 ASTRA study for Stargardt ... SB-007 is the first gene therapy in clinical development designed to restore expression of the full-length ABCA4 protein across all Stargardt ...

7. prnewswire.com prnewswire.com/news-releases/splicebio-announces-us-fda-ind-clearance-of-sb-007-to-commence-phase-12-clinical-study-in-patients-with-stargardt-disease-302329356.html

SpliceBio Announces U.S. FDA IND Clearance of SB-007 ... SB-007 is the only IND-cleared, clinical-stage therapeutic addressing the root cause of Stargardt disease with the potential to treat all ...

8. splice.bio splice.bio/splicebio-announces-first-patient-dosed-in-phase-1-2-astra-study-of-sb-007-a-dual-aav-gene-therapy-for-stargardt-disease/

SpliceBio Announces First Patient Dosed in Phase 1/2 ... In December 2024, SB-007 received FDA IND clearance, marking the first-ever clearance for a dual AAV gene therapy in Stargardt disease.