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- Title
Phase 2 Trial Evaluating Minocycline for Geographic Atrophy in Age-Related Macular Degeneration: A Nonrandomized Controlled Trial.
- Authors
Keenan, Tiarnan D. L.; Bailey, Clare; Abraham, Maria; Orndahl, Christine; Menezes, Supriya; Bellur, Sunil; Arunachalam, Thilaka; Kangale-Whitney, Cathy; Srinivas, Sowmya; Karamat, Ayesha; Nittala, Muneeswar; Cunningham, Denise; Jeffrey, Brett G.; Wiley, Henry E.; Thavikulwat, Alisa T.; Sadda, SriniVas; Cukras, Catherine A.; Chew, Emily Y.; Wong, Wai T.
- Abstract
This nonrandomized controlled trial investigates the safety and efficacy of oral minocycline in the treatment of geographic atrophy in age-related macular degeneration. Key Points: Question: What are the safety and possible anatomic efficacy of oral minocycline, a microglial inhibitor, for the treatment of geographic atrophy (GA) in age-related macular degeneration (AMD)? Findings: In this phase 2 nonrandomized controlled trial that included 37 participants, the mean square root GA enlargement rate was 0.31 mm per year during the 9-month run-in phase and 0.28 mm per year during the 24-month treatment phase. The difference was not significant. Meaning: Results suggest that oral minocycline at this dose likely was not associated with slower rate of enlargement of GA in AMD. 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 μm 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.
- Publication
JAMA Ophthalmology, 2024, Vol 142, Issue 4, p345
- ISSN
2168-6165
- Publication type
Article
- DOI
10.1001/jamaophthalmol.2024.0118