Table 1

Summary of therapeutic trials for Stargardt disease (STGD1; ABCA4 retinopathy) identifierTitleSummary results
Inhibition of vitamin A dimerisationALK-001OralPhase 2 tong-term follow-upNCT04239625Open-Label Extension: Tolerability and Effects of ALK-001 on Stargardt DiseaseActive study
Inhibition of vitamin A dimerisationALK-001OralPhase 2NCT02402660Phase 2 Tolerability and Effects of ALK-001 on Stargardt DiseaseReduction in growth rate of atrophic lesions, no change in BCVA, no reports of night blindness or impaired dark adaptation
Inhibition of vitamin A dimerisationALK-001OralPhase 1NCT02230228Phase 1 Safety Study of ALK-001 in Healthy Volunteers
RBP4 InhibitionSTG-001OralPhase 2NCT04489511Study of STG-001 in Subjects With Stargardt DiseaseReported AEs: 6 patients low dose: 1 dry eye, 1 subretinal fluid, 1 skin disorder;
4 patients high dose: 1 chromatopsia, 1 delayed dark adaptation, 2 night blindness, 1 visual impairment, 1 dry skin
RBP4 InhibitionTinlarebantOralPhase 3NCT05244304Study to Evaluate the Safety and Efficacy of Tinlarebant in the Treatment of Stargardt Disease in Adolescent Subjects Lesion(s) in Adolescent Subjects With STGD1Active study
RBP4 InhibitionTinlarebantOralPhase 1 Phase 2NCT05266014Dose-finding Study Followed by 2 year Extension Study to Evaluate Safety and Tolerability of Tinlarebant in Adolescent Subjects With Stargardt DiseasePreliminary safety results: 9/13 patients delayed dark adaptation, 9/13 xanthopsia/chromatopsia, 1/13 night vision impairment. No clinically significant findings in relation to general health. 8/13 gain in BCVA, trend for preventing/slowing atrophy on FAF, 6/13 narrowing of EZ defect
RBP4 InhibitionVutrisiranSubcutaneousPhase 3Not yet registeredTHEIA-A: A Phase 3 Global, Randomised, Double-Masked, Placebo-Controlled Study to Evaluate the Clinical Outcomes, Efficacy and Safety of Vutrisiran in Patients with Stargardt Disease Type 1 (STGD1)Upcoming trial
Inhibition of visual cycle (RPE65)EmixustatOralPhase 3NCT03772665Safety and Efficacy of Emixustat in Stargardt DiseaseNo meaningful differences between treatment groups regarding macular atrophy
Inhibition of visual cycle (RPE65)EmixustatOralPhase 2NCT03033108Pharmacodynamic Study of Emixustat Hydrochloride in Subjects With Macular Atrophy Secondary to Stargardt DiseaseDose-dependent suppression of rod b-wave amplitude recovery post photobleaching, confirming emixustat’s biological activity. AE: dark adaptation (11/23, 47.8%), erythropsia (5/23, 21.7%), vision blurred (4/23, 17.4%), photophobia (3/23, 13%), visual impairment (3/23, 13%), headache (2/23)
Inhibition of visual cycle4-MethylpyrazoleIntravenousPhase 1NCT00346853Phase 1 Pilot Study of 4-MP to Treat Stargardt Macular DystrophyNo effect on dark adaptation in healthy probands, further studies suspended because substance doesn't seem to inhibit the visual cycle strong enough
Removal of lipofuscinSoraprazanOralPhase 2EudraCT 2018-001496-20A multinational, multi-centre, double-masked, placebo-controlled proof of concept trial to evaluate the safety and efficacy of oral soraprazan in Stargardt diseaseActive study
Induce AutophagyMetforminOralPhase 1 Phase 2NCT04545736Oral Metformin for Treatment of ABCA4 RetinopathyActive study
Inhibition of complement C5ZimuraIntravitrealPhase 2NCT03364153Zimura Compared with Sham in Patients With Autosomal Recessive Stargardt Disease (STGD1)Active study
SupplementsOmega-3 Fatty AcidsOralNCT03297515Therapeutic Potential of Omega-3 Fatty Acids Supplementation in Dry Macular Degeneration and Stargardt DiseaseIncrease of BCVA in the active group after 24 weeks, score of a questionnaire on perceived vision and subjective mood higher in the active group at week 24, CAVE: patient cohort Stargardt+dry AMD, results not shown separately
SupplementsDocosahexaenoic acid (DHA)OralNCT00420602DHA Supplementation in Patients With STGD3No beneficial effect over 8 years, poor compliance
SupplementsDHAOralPhase 1NCT00060749Effect of DHA Supplements on Macular Function in Patients With Stargardt Macular Dystrophy and Stargardt-like Macular DystrophyNo effect on macular function
SupplementsSaffronOralPhase 1 Phase 2NCT01278277Saffron Supplementation in Stargardt’s DiseaseShort-term supplementation was well tolerated and had no detrimental effects on the electroretinographic responses of the central retina
Gene therapy (ABCA4)SAR422459SubretinalPhase 1 Phase 2 Follow-upNCT01736592Phase I/II Follow-up Study of SAR422459 in Patients With Stargardt’s Macular DegenerationTreatment was well tolerated. No clinically significant changes in visual function tests were found to be attributable to the treatment. Reduction of flecks in one eye. 1 case of ocular hypertension. 27% of treated eyes showed exacerbation of retinal pigment epithelium atrophy on FAF.
Gene therapy (ABCA4)SAR422459SubretinalPhase 1 Phase 2NCT01367444Phase I/IIA Study of SAR422459 in Participants With Stargardt’s Macular DegenerationFavourable safety profile
OptogeneticsvMCO-010IntravitrealPhase 2NCT05417126Safety and Effects of a Single Intravitreal Injection of vMCO-010 Optogenetic Therapy in Subjects With Stargardt DiseaseActive study
Stem cellshESC Derived RPE (MA09-hRPE)SubretinalPhase 2 Follow-upNCT02941991A Follow-up Study to Determine the Safety and Tolerability of Sub-retinal Transplantation of Human Embryonic Stem Cell Derived Retinal Pigmented Epithelial (hESC-RPE) Cells in Patients With Stargardt’s Macular Dystrophy (SMD)Active study
Stem cellshESC Derived RPE (MA09-hRPE)SubretinalPhase 1 Phase 2NCT01345006Sub-retinal Transplantation of hESC Derived RPE (MA09-hRPE) Cells in Patients With Stargardt’s Macular DystrophyNo evidence of adverse proliferation, rejection, or serious ocular or systemic safety issues related to the transplanted tissue. 13/18 px (72%) had patches of increasing subretinal pigmentation. BCVA improved in ten eyes, improved or remained the same in seven eyes, and decreased by more than ten letters in one eye, no similar improvements in untreated FE. Vision-related quality-of-life measures increased 3–12 months after transplantation.
Stem cellshESC Derived RPE (MA09-hRPE)SubretinalFollow-upNCT02445612Long Term Follow-up of Sub-retinal Transplantation of hESC Derived RPE Cells in Stargardt Macular Dystrophy PatientsActive study
Stem cellshESC Derived RPE (MA09-hRPE)SubretinalPhase 1 Phase 2NCT01469832Safety and Tolerability of Sub-retinal Transplantation of hESC-RPE Cells in Patients With SMDFocal areas of subretinal hyperpigmentation, no evidence of uncontrolled proliferation or inflammatory responses. No meaningful improvements in BCVA, no benefit in microperimetry at 12 months, one case of localised retinal thinning and reduced sensitivity in the area of hyperpigmentation. No significant change in participant-reported quality of life.
Stem cellshESC Derived RPE (MA09-hRPE)SubretinalPhase 1NCT01625559A Phase I, Open-Label, Prospective Study to Determine the Safety and Tolerability of Sub-retinal Transplantation of hESC-RPE (MA09-hRPE) Cells in Patients With SMDNo serious AEs occurred throughout the 3 year period following the injection of hESC-RPE cells. The functional and anatomical results were favourable, compared with the natural course of SMD reported in the ProgStar study.
Stem cellshESC Derived RPEsubretinalPhase 1 Phase 2NCT02749734Clinical Study of Subretinal Transplantation of Human Embryo Stem Cell Derived Retinal Pigment Epitheliums in Treatment of Macular Degeneration DiseasesActive study
Stem cellshESC Derived RPEsubretinalPhase 1 Phase 2NCT02903576Stem Cell Therapy for Outer Retinal Degenerations (sub retinal injections vs hESC RPE seeded on a polymeric substrate implanted in the subretinal space)Active study
Stem cellsAutologous bone marrow-isolated stem/progenitor cellsIntravitrealPhase 1NCT03772938Stem Cells Therapy in Degenerative Diseases of the RetinaNo results from STGD group to date
Stem cellsAutologous bone marrow derived stem cells (BMSC)Retrobulbar, subtenon, intravitreal, intraocular, subretinal and intravenousNCT03011541Stem Cell Ophthalmology Treatment (SCOT) Study IIActive study
Stem cellsAutologous BMSCRetrobulbar, subtenon, intravitreal, intraocular, subretinal and intravenousNCT01920867Stem Cell Ophthalmology Treatment Study21/34 eyes (61.8%) improved, 8/34 eyes (23.5%) remained stable, and 5/34 eyes (14.7%) showed continued progression. The average central vision improvement following treatment was 17.96% and ranged up to 80.5%. Of 17 patients treated, 13/17px (76.5%) showed visual acuity improvement in one or both eyes, 3/17px (17.6%) showed no net loss, and 1px worsened as a consequence of disease progression; 94.1% of patients had improved vision or remained stable. There were no AEs.
  • AE, adverse event; AMD, age-related macular degeneration; BCVA, best-corrected VA; FAF, fundus autofluorescence ; VA, visual acuity.