Safety and Efficacy of Subretinal Administration of AAVB-039 in Participants with Stargardt Disease (STGD1): A Phase 1/2 Open-Label, Multicenter Study

The primary objectives of this study are to evaluate the safety, tolerability, and dose response of subretinal administration of AAVB-039 to establish a preferred dose level, followed by an assessment of the efficacy of the selected dose in participants with Stargardt disease. Secondary objectives include:

• The determination of preliminary efficacy during the initial phase.
• The ongoing evaluation of safety and tolerability at the preferred dose level.
• The continued assessment of clinical efficacy at the preferred dose level.

This clinical trial involves a total of 54 participants diagnosed with Stargardt disease. The study population includes both male and female patients. Age requirements vary between study components, with Part A enrolling individuals aged 18 to 55 years and Part B enrolling individuals aged 8 to 55 years. Selection is based on the presence of biallelic mutations in the ABCA4 gene, confirmed by a CLIA-certified laboratory. Participants must demonstrate adequate clarity of ocular media and pupillary dilation to facilitate imaging of macular atrophy. Specific visual requirements include defined ranges for best-corrected visual acuity and the presence of a continuous absence of the ellipsoid zone band in the fovea as measured by optical coherence tomography. The study also utilizes fundus autofluorescence to assess the area of atrophy within the trial eye.

This open-label, multicenter, two-part study is designed to evaluate the safety and efficacy of AAVB-039 via subretinal administration in individuals diagnosed with Stargardt disease. Part A is an ascending dose study intended to determine the safety, tolerability, and preferred dose level of the investigational product. Part B is a controlled trial designed to assess the efficacy of the preferred dose. The study involves a screening process to confirm the presence of biallelic mutations in the ABCA4 gene and specific ophthalmic characteristics, such as macular atrophy and visual acuity levels. Following the administration of the solution for injection, participants will undergo longitudinal follow-up visits to monitor for adverse events and changes in clinical parameters. Primary efficacy endpoints for Part B include the rate of change in the area of ellipsoid zone loss at 12 months. Secondary endpoints involve assessments of fundus autofluorescence, microperimetry, and best corrected visual acuity over durations of up to 60 months. The total study duration is estimated to extend through September 2031.

AAVB-039 is an experimental solution for injection. This therapeutic agent consists of a combination of two adeno-associated viral vectors of serotype 8 containing the 5'- and the 3'- half coding sequences of human ABCA4 fused to inteins. The administration route for this substance is subretinal.

The efficacy of AAVB-039 in the treatment of Stargardt disease will be evaluated through several parameters. In Part B of the study, the primary efficacy endpoint is the rate of change in the area of ellipsoid zone (EZ) loss at 12 months.

Secondary efficacy assessments include the following measures conducted at 12, 24, and 60 months:

• Area of atrophy as assessed via short wavelength fundus autofluorescence (SW-FAF).
• Macular sensitivity assessed via microperimetry.
• Best corrected visual acuity (BCVA) letter score.
• Low-luminance visual acuity (LLVA) letter score.

The rate of change for the area of ellipsoid zone loss will be specifically monitored at 24 and 60 months.