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Phase 2 Trial Evaluating Minocycline for Geographic Atrophy in Age-Related Macular Degeneration: A Nonrandomized Controlled Trial

03/2024

Journal Article

Authors:
Keenan, T. D. L.; Bailey, C.; Abraham, M. ; Orndahl, C. ; Menezes, S.; Bellur, S.; Arunachalam, T.; Kangale-Whitney, C. ; Srinivas, S.; Karamat, A.; Nittala, M.; Cunningham, D.; Jeffrey, B. G.; Wiley, H. E.; Thavikulwat, A. T.; Sadda, S.; Cukras, C. A.; Chew, E. Y.; Wong, W. T.

Journal:
JAMA Ophthalmol

PMID:
38483382

URL:
https://www.ncbi.nlm.nih.gov/pubmed/38483382

DOI:
10.1001/jamaophthalmol.2024.0118

Keywords:
oral minocycline geographic atrophy microglial inhibitor age-related macular degeneration

Abstract:
IMPORTANCE: Existing therapies to slow geographic atrophy (GA) enlargement in age-related macular degeneration (AMD) have relatively modest anatomic efficacy, require intravitreal administration, and increase the risk of neovascular AMD. Additional therapeutic approaches are desirable. OBJECTIVE: To evaluate the safety and possible anatomic efficacy of oral minocycline, a microglial inhibitor, for the treatment of GA in AMD. DESIGN, SETTING, AND PARTICIPANTS: This was a phase 2, prospective, single-arm, 45-month, nonrandomized controlled trial conducted from December 2016 to April 2023. Patients with GA from AMD in 1 or both eyes were recruited from the National Institutes of Health (Bethesda, Maryland) and Bristol Eye Hospital (Bristol, UK). Study data were analyzed from September 2022 to May 2023. INTERVENTION: After a 9-month run-in phase, participants began oral minocycline, 100 mg, twice daily for 3 years. MAIN OUTCOMES AND MEASURES: The primary outcome measure was the difference in rate of change of square root GA area on fundus autofluorescence between the 24-month treatment phase and 9-month run-in phase. RESULTS: Of the 37 participants enrolled (mean [SD] age, 74.3 [7.6] years; 21 female [57%]), 36 initiated the treatment phase. Of these participants, 21 (58%) completed at least 33 months, whereas 15 discontinued treatment (8 by request, 6 for adverse events/illness, and 1 death). Mean (SE) square root GA enlargement rate in study eyes was 0.31 (0.03) mm per year during the run-in phase and 0.28 (0.02) mm per year during the treatment phase. The primary outcome measure of mean (SE) difference in enlargement rates between the 2 phases was -0.03 (0.03) mm per year (P = .39). Similarly, secondary outcome measures of GA enlargement rate showed no differences between the 2 phases. The secondary outcome measures of mean difference in rate of change between 2 phases were 0.2 letter score per month (95% CI, -0.4 to 0.9; P = .44) for visual acuity and 0.7 mum per month (-0.4 to 1.8; P = .20) for subfoveal retinal thickness. Of the 129 treatment-emergent adverse events among 32 participants, 49 (38%) were related to minocycline (with no severe or ocular events), including elevated thyrotropin level (15 participants) and skin hyperpigmentation/discoloration (8 participants). CONCLUSIONS AND RELEVANCE: In this phase 2 nonrandomized controlled trial, oral minocycline was not associated with a decrease in GA enlargement over 24 months, compared with the run-in phase. This observation was consistent across primary and secondary outcome measures. Oral minocycline at this dose is likely not associated with slower rate of enlargement of GA in AMD.

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