A Phase I/IIa Dose Escalation Safety Study of Subretinally Injected SAR422459, Administered to Patients with Stargardt's Macular Degeneration.

Patients must meet ALL of the following criteria to be considered for enrolment into this study:;1. Signed and dated written informed consent obtained from the patient and/or the patient*s legally acceptable representative, if applicable, in accordance with the local regulations.;2. Diagnosis of SMD, with at least one pathogenic mutant ABCA4 allele on each chromosome, confirmed by direct sequencing.;3. Women of childbearing potential must have a negative pregnancy test at day -1 and agree to use an effective form of contraception for at least three months such as the contraceptive pill or intra uterine device, or be surgically sterile or postmenopausal, with the last menstrual period being over two years prior to enrolment (partners of study patients must agree to use barrier contraception for at least three months after SAR422459 administration).;4. Males must agree with their partner to use two forms of contraception, including one barrier method for at least three months following SAR422459 administration if their partner is of childbearing potential, or must be surgically sterile.;Specific Inclusion Criteria Patient Group D:;- Symptomatic patients (6 years and older) with childhood or young adult onset Stargardt's Macular Degeneration (eg, before age 26) with at least one pathogenic mutant ABCA4 allele on each chromosome confirmed by direct sequencing and co-segregation analysis within the patient*s family.;- Visual acuity of *20/200 in both eyes at the time of the screening visit.;- Patients are anticipated to experience rapid deterioration in visual function and/or retinal structure in the opinion of the study Investigator.

1. Pre-existing eye conditions that would preclude the planned surgery or interfere with the interpretation of study endpoints: glaucoma or other primary optic neuropathy that has resulted in significant visual field loss, corneal or significant lens opacities, active uveitis, retinopathy and maculopathy (other than that from Stargardt disease) that in the opinion of the investigator is causing significant visual loss, myopia greater than 8 diopters spherical equivalent.;2. Cataract surgery with intraocular lens implantation within 6 months of enrolment.;3. Aphakia or prior vitrectomy in the study eye.;4. Concomitant systemic diseases including those in which the disease itself, or the treatment for the disease, can alter ocular function. For instance malignancies whose treatment could affect central nervous system function, diabetes, juvenile rheumatoid arthritis or sickle cell disease.;5. Any intraocular surgery (other than study procedure) or laser in either eye planned within 6 months of Day 0.;6. Any contraindication to pupil dilation in either eye.;7. Any known allergy to any component of the delivery vehicle or diagnostic agents used during the study (e.g., fluorescein, dilation drops), or medications planned for use in the peri-operative period particularly topical, injected or systemic corticosteroids.;8. Any injectable intravitreal treatment to the treated eye or intravitreal device in the treated eye within 6 months prior to screening.;9. Any periocular injections of corticosteroids to the treated eye within 4 months prior to screening.;10. Laboratory test abnormalities or abnormalities in electrocardiogram, chest X-rays that in the opinion of the PI would make the patient unsuitable for participation in the study.;11. Significant intercurrent illness or infection during the 28 days prior to enrolment.;12. Pre-menopausal or non-surgically sterile women who are unwilling to use an effective form of contraception such as the contraceptive pill or intrauterine device.;13. Men or women who do not agree to use barrier contraception according to the inclusion criteria.;14. Alcohol or other substance abuse.;15. Contraindications to use of anesthesia (local or general, as appropriate).;16. Concurrent anti-retroviral therapy that would inactivate the investigational agent.;17. History of any investigational agent within 28 days prior to SAR422459 administration.;18. Participation in a prior ocular gene transfer therapy study.;19. Enrolment in any other clinical treatment study, for any condition, including those relating to SMD, throughout the duration of the SAR422459 TDU13583 study participation.;20. Current or anticipated treatment with anticoagulant therapy or the use of anticoagulation
therapy within the four weeks prior to surgery.;21. A past medical history of HIV or hepatitis A, B or C infection.;22. Inability to comply with the demands of the study.;23. Women who are pregnant or are breastfeeding.;24. History or signs consistent with unilateral amblyopia (strabismic, anisometropic or stimulus deprivation).