Evaluating a new gene therapy for Stargardt Disease

A Phase 1/2, First-in-Human, Open-label, Assessor-Masked, Randomized, Controlled, Dose Escalation/Expansion Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of a Subretinal Injection of SB-007 in Subjects With Stargardt Disease (STGD1) Caused by Bi-Allelic Autosomal Recessive Mutations in the ATP Binding Cassette Subfamily A Member 4 (ABCA4) Gene

This study is testing a new gene therapy to see if it can safely help people with Stargardt Disease Type 1 slow down or improve their vision loss.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 57 (estimated)
• Ages: 12 Years to 65 Years
• Sex: All
• Sponsor: Splice Bio (Industry-sponsored)
• Locations: 5 sites (Aurora, Colorado and 4 other locations)
• Trial ID: NCT06942572 on ClinicalTrials.gov

What this trial studies

This Phase 1/2 clinical trial aims to assess the safety, tolerability, and preliminary efficacy of a gene therapy called SB-007 administered via subretinal injection in patients with Stargardt Disease Type 1 (STGD1). The study will enroll approximately 57 participants and will follow them for 96 weeks after a single treatment to monitor outcomes. The trial is designed to determine the appropriate dosage and gather initial data on the therapy's effectiveness in slowing or reversing vision loss associated with this inherited retinal dystrophy.

Who should consider this trial

Good fit: Ideal candidates for this study are adolescents and adults aged 12 to 65 with a confirmed diagnosis of Stargardt Disease Type 1 due to specific genetic mutations.

Not a fit: Patients with Stargardt Disease who do not have the required bi-allelic pathogenic variants in the ABCA4 gene may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a new treatment option for patients suffering from Stargardt Disease, potentially improving their vision and quality of life.

How similar studies have performed: Other studies exploring gene therapies for inherited retinal diseases have shown promising results, indicating potential for success in this novel approach.

Eligibility criteria

Inclusion Criteria:

To be eligible for study participation, subjects must meet the following criteria:

1. Provide written consent. Subjects under legal age will also provide informed assent according to guidelines set forth by the same.
2. Are male or female adolescents and adults, aged as follows:

   1. In Part A, subjects will be ≥18 to ≤65\* years (inclusive)
   2. In Part B, subject age is planned as ≥12 to ≤65\* years (inclusive) \*Subjects aged \>65 years may be eligible in Parts A and B, following discussion with, and approval by, the Medical Monitor.
3. Are able to understand and comply with the study procedures.
4. Have a diagnosis of STGD1 caused by bi-allelic pathogenic, or likely pathogenic, variants in the ABCA4 gene confirmed genotypically by an accredited genetic testing laboratory
5. Clinical evidence consistent with Stargardt Disease type 1.
6. For women of child-bearing potential (WOCBP), have a negative pregnancy test at Screening and, if due to receive active treatment, at Day 0.
7. For both WOCBP and male subjects (or their female partners who are of child-bearing potential), agree to either strict abstinence or, if sexually active, use an acceptable contraception measure for 3 months from Day 0
8. Must have clear ocular media and adequate pupillary dilation in the study eye, including no allergy to dilating eyedrops, to permit good quality retinal imaging.
9. Fulfil visual acuity criteria based on ETDRS letter chart
10. Fulfil baseline lesion size measurement, as measured by the Reading Center
11. Evidence of disease progression as determined by the Medical Monitor following consultation with the Investigator.

Exclusion Criteria:

Subjects must be excluded from participating in the study if they:

1. Have had any intraocular surgery (including cataract surgery) or thermal laser within 90 days of the Screening Visit or planned intraocular surgery (including cataract surgery) or thermal laser during the period of the study, in the study eye.
2. Have had any major surgical procedure within 30 days of the Screening Visit or planned or anticipated major surgery during the period of the study.
3. Have two pathogenic or likely pathogenic variants in IRD genes (other than ABCA4) or a single pathogenic or likely pathogenic variant in autosomal dominant or X-linked IRD genes.
4. Have a history of amblyopia in the study eye.
5. Are unwilling to stop taking the following products at Screening and throughout the study:

   1. Supplements containing vitamin A or beta-carotene, liver-based products.
   2. Prescription oral retinoids. Topical products containing vitamin A or retinoids are not exclusionary.
6. Have any ophthalmic history of gene therapy, stem cell therapy, surgical implantation of prosthetic retinal chips, or intravitreal or sub-retinal or supra-choroidal injections.
7. Have received any investigational therapy within 90 days of the Screening Visit or 5 half-lives, whichever is longer.
8. Have known serious allergies to the fluorescein dye that might be used to measure IOP, ocular dilating drops, topical ocular anesthetic, steroid medication, or components of the SB-007 formulation.
9. Have any significant ocular or non-ocular disease/disorder which, in the opinion of the Investigator and with concurrence of the Medical Monitor, may either put the subject at risk because of participation in the study, may influence the results of the study, or affect the subject's ability to participate in the study.
10. Are an immediate family member (e.g., child, sibling) of the Sponsor or study site personnel.

Where this trial is running

Aurora, Colorado and 4 other locations

• UCHealth Sue Anschutz-Rodgers Eye Center, — Aurora, Colorado, United States (Recruiting)
• Bascom Palmer Eye Institute — Miami, Florida, United States (Recruiting)
• Massachusetts Eye and Ear Infirmary — Boston, Massachusetts, United States (Recruiting)
• Oregon Health & Science University — Portland, Oregon, United States (Recruiting)
• Retina Foundation of the Southwest — Dallas, Texas, United States (Recruiting)

Study contacts

• Study coordinator: SpliceBio

Conditions Stargardt Disease; Stargardt Macular Degeneration; Stargardt Macular Dystrophy; Gene Therapy; SB-007; Splicebio; Stargardt; Stargardts Disease