Phase 1/2 Open-Label Dose-Escalation Study to Evaluate Safety of a Single Intravitreal Injection of RTx-021 in Patients With Stargardt Disease

This Phase 1/2, open-label, non-randomized, sequential assignment, first-in-human dose-escalation study is to evaluate the safety and preliminary efficacy of a single, uniocular intravitreal injection of an investigational optogenetic gene therapy, RTx-021, in patients with Stargardt Disease. Up to 3 dose cohorts of RTx-021 are planned, and each cohort will consist initially of 3 patients. The study is a traditional dose escalation design with the potential for cohort expansion and is intended to support dose selection for further clinical development. Patients will receive a single, unilateral intravitreal injection of RTx-021 in the study eye and be followed for 5 years with visits being more frequent in the initial 12 months after treatment.

Inclusion criteria

• Male and female patients >= 16 years of age
• Able to comply with the study visit schedule and all protocol assessments
• Diagnosis of Stargardt Disease (genetic testing required)
• Study eye and fellow eye Best Corrected Visual Acuity meeting study criteria
• Presence of retinal ganglion cells and/or retinal nerve fiber layer on Spectral Domain Optical Coherence Tomography testing at Screening confirmed by central image reading center
• Adequate organ function and general good health

Exclusion criteria

• Participation in a clinical study (ocular or non-ocular) with an investigational drug, agent, or therapy in the past six months
• Concurrent participation in another interventional clinical ocular study
• Prior receipt of any gene therapy (ocular or other), retinal implant, or ocular cell therapy
• Pre-existing eye conditions in either eye that would preclude the planned treatment or are significant enough to interfere with the interpretation of study endpoints or procedural complications
• Known steroid responders if their intraocular pressure was not able to be managed effectively with topical pressure-lowering medications after prior use of steroid medications
• Complicating systemic diseases including those in which the disease itself, or the treatment of the disease, can alter ocular and/or central nervous system function (e.g. radiation treatment of the orbit; leukemia with optic nerve involvement)
• Any immunological response dysfunction including, immuno-compromising diseases or use of immunosuppressive medications, among others
• Cataract or other ocular (including refractive) surgery, intraocular and/or peri-ocular injection in either eye within the prior four months (i.e. 120 days) prior to screening
• Prior vitrectomy or aphakia in the study eye
• Known sensitivity to any component of the study treatment or contraindication to medications planned for use in the peri-procedural period (e.g. povidone-iodine to prep for intravitreal injection)
• Known contraindication to prophylactic steroid regimen
• Current pregnancy or breastfeeding
• Any other condition that would not allow the patient to complete follow-up examinations during the study