Summary of therapeutic trials for Stargardt disease (STGD1; ABCA4 retinopathy)
| Mechanism | Treatment | Route | Phase | ClinicalTrials.gov identifier | Title | Summary results |
| Inhibition of vitamin A dimerisation | ALK-001 | Oral | Phase 2 tong-term follow-up | NCT04239625 | Open-Label Extension: Tolerability and Effects of ALK-001 on Stargardt Disease | Active study |
| Inhibition of vitamin A dimerisation | ALK-001 | Oral | Phase 2 | NCT02402660 | Phase 2 Tolerability and Effects of ALK-001 on Stargardt Disease | Reduction in growth rate of atrophic lesions, no change in BCVA, no reports of night blindness or impaired dark adaptation |
| Inhibition of vitamin A dimerisation | ALK-001 | Oral | Phase 1 | NCT02230228 | Phase 1 Safety Study of ALK-001 in Healthy Volunteers | |
| RBP4 Inhibition | STG-001 | Oral | Phase 2 | NCT04489511 | Study of STG-001 in Subjects With Stargardt Disease | Reported 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 Inhibition | Tinlarebant | Oral | Phase 3 | NCT05244304 | Study to Evaluate the Safety and Efficacy of Tinlarebant in the Treatment of Stargardt Disease in Adolescent Subjects Lesion(s) in Adolescent Subjects With STGD1 | Active study |
| RBP4 Inhibition | Tinlarebant | Oral | Phase 1 Phase 2 | NCT05266014 | Dose-finding Study Followed by 2 year Extension Study to Evaluate Safety and Tolerability of Tinlarebant in Adolescent Subjects With Stargardt Disease | Preliminary 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 Inhibition | Vutrisiran | Subcutaneous | Phase 3 | Not yet registered | THEIA-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) | Emixustat | Oral | Phase 3 | NCT03772665 | Safety and Efficacy of Emixustat in Stargardt Disease | No meaningful differences between treatment groups regarding macular atrophy |
| Inhibition of visual cycle (RPE65) | Emixustat | Oral | Phase 2 | NCT03033108 | Pharmacodynamic Study of Emixustat Hydrochloride in Subjects With Macular Atrophy Secondary to Stargardt Disease | Dose-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 cycle | 4-Methylpyrazole | Intravenous | Phase 1 | NCT00346853 | Phase 1 Pilot Study of 4-MP to Treat Stargardt Macular Dystrophy | No effect on dark adaptation in healthy probands, further studies suspended because substance doesn't seem to inhibit the visual cycle strong enough |
| Removal of lipofuscin | Soraprazan | Oral | Phase 2 | EudraCT 2018-001496-20 | A multinational, multi-centre, double-masked, placebo-controlled proof of concept trial to evaluate the safety and efficacy of oral soraprazan in Stargardt disease | Active study |
| Induce Autophagy | Metformin | Oral | Phase 1 Phase 2 | NCT04545736 | Oral Metformin for Treatment of ABCA4 Retinopathy | Active study |
| Inhibition of complement C5 | Zimura | Intravitreal | Phase 2 | NCT03364153 | Zimura Compared with Sham in Patients With Autosomal Recessive Stargardt Disease (STGD1) | Active study |
| Supplements | Omega-3 Fatty Acids | Oral | NCT03297515 | Therapeutic Potential of Omega-3 Fatty Acids Supplementation in Dry Macular Degeneration and Stargardt Disease | Increase 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 | |
| Supplements | Docosahexaenoic acid (DHA) | Oral | NCT00420602 | DHA Supplementation in Patients With STGD3 | No beneficial effect over 8 years, poor compliance | |
| Supplements | DHA | Oral | Phase 1 | NCT00060749 | Effect of DHA Supplements on Macular Function in Patients With Stargardt Macular Dystrophy and Stargardt-like Macular Dystrophy | No effect on macular function |
| Supplements | Saffron | Oral | Phase 1 Phase 2 | NCT01278277 | Saffron Supplementation in Stargardt’s Disease | Short-term supplementation was well tolerated and had no detrimental effects on the electroretinographic responses of the central retina |
| Gene therapy (ABCA4) | SAR422459 | Subretinal | Phase 1 Phase 2 Follow-up | NCT01736592 | Phase I/II Follow-up Study of SAR422459 in Patients With Stargardt’s Macular Degeneration | Treatment 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) | SAR422459 | Subretinal | Phase 1 Phase 2 | NCT01367444 | Phase I/IIA Study of SAR422459 in Participants With Stargardt’s Macular Degeneration | Favourable safety profile |
| Optogenetics | vMCO-010 | Intravitreal | Phase 2 | NCT05417126 | Safety and Effects of a Single Intravitreal Injection of vMCO-010 Optogenetic Therapy in Subjects With Stargardt Disease | Active study |
| Stem cells | hESC Derived RPE (MA09-hRPE) | Subretinal | Phase 2 Follow-up | NCT02941991 | A 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 cells | hESC Derived RPE (MA09-hRPE) | Subretinal | Phase 1 Phase 2 | NCT01345006 | Sub-retinal Transplantation of hESC Derived RPE (MA09-hRPE) Cells in Patients With Stargardt’s Macular Dystrophy | No 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 cells | hESC Derived RPE (MA09-hRPE) | Subretinal | Follow-up | NCT02445612 | Long Term Follow-up of Sub-retinal Transplantation of hESC Derived RPE Cells in Stargardt Macular Dystrophy Patients | Active study |
| Stem cells | hESC Derived RPE (MA09-hRPE) | Subretinal | Phase 1 Phase 2 | NCT01469832 | Safety and Tolerability of Sub-retinal Transplantation of hESC-RPE Cells in Patients With SMD | Focal 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 cells | hESC Derived RPE (MA09-hRPE) | Subretinal | Phase 1 | NCT01625559 | A 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 SMD | No 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 cells | hESC Derived RPE | subretinal | Phase 1 Phase 2 | NCT02749734 | Clinical Study of Subretinal Transplantation of Human Embryo Stem Cell Derived Retinal Pigment Epitheliums in Treatment of Macular Degeneration Diseases | Active study |
| Stem cells | hESC Derived RPE | subretinal | Phase 1 Phase 2 | NCT02903576 | Stem 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 cells | Autologous bone marrow-isolated stem/progenitor cells | Intravitreal | Phase 1 | NCT03772938 | Stem Cells Therapy in Degenerative Diseases of the Retina | No results from STGD group to date |
| Stem cells | Autologous bone marrow derived stem cells (BMSC) | Retrobulbar, subtenon, intravitreal, intraocular, subretinal and intravenous | NCT03011541 | Stem Cell Ophthalmology Treatment (SCOT) Study II | Active study | |
| Stem cells | Autologous BMSC | Retrobulbar, subtenon, intravitreal, intraocular, subretinal and intravenous | NCT01920867 | Stem Cell Ophthalmology Treatment Study | 21/34 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.