June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
A Phase II Trial Evaluating Oral Minocycline in the Treatment of Geographic Atrophy in Age-Related Macular Degeneration
Author Affiliations & Notes
  • Tiarnan D L Keenan
    National Eye Institute, Bethesda, Maryland, United States
  • Clare C Bailey
    Bristol Eye Hospital, Bristol, Bristol, United Kingdom
  • Sunil Bellur
    National Eye Institute, Bethesda, Maryland, United States
  • Thilaka Arunachalam
    National Eye Institute, Bethesda, Maryland, United States
  • Cathy Kangale-Whitney
    National Eye Institute, Bethesda, Maryland, United States
  • Maria Abraham
    The Emmes Company LLC, Rockville, Maryland, United States
  • Christine Orndahl
    The Emmes Company LLC, Rockville, Maryland, United States
  • Supriya Menezes
    The Emmes Company LLC, Rockville, Maryland, United States
  • Brett Jeffrey
    National Eye Institute, Bethesda, Maryland, United States
  • Henry Wiley
    Genentech Inc, South San Francisco, California, United States
  • Alisa Thavikulwat
    National Eye Institute, Bethesda, Maryland, United States
  • Catherine Cukras
    National Eye Institute, Bethesda, Maryland, United States
  • Emily Y. Chew
    National Eye Institute, Bethesda, Maryland, United States
  • Wai T Wong
    Janssen Research and Development LLC, Brisbane, California, United States
  • Footnotes
    Commercial Relationships   Tiarnan Keenan None; Clare Bailey None; Sunil Bellur None; Thilaka Arunachalam None; Cathy Kangale-Whitney None; Maria Abraham The Emmes Company LLC, Code E (Employment); Christine Orndahl The Emmes Company LLC, Code E (Employment); Supriya Menezes The Emmes Company LLC, Code E (Employment); Brett Jeffrey None; Henry Wiley Genentech, Code E (Employment); Alisa Thavikulwat None; Catherine Cukras None; Emily Chew None; Wai Wong Janssen Research and Development LLC, Code E (Employment)
  • Footnotes
    Support  National Eye Institute Intramural Research Program, National Institutes of Health
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 5058. doi:
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      Tiarnan D L Keenan, Clare C Bailey, Sunil Bellur, Thilaka Arunachalam, Cathy Kangale-Whitney, Maria Abraham, Christine Orndahl, Supriya Menezes, Brett Jeffrey, Henry Wiley, Alisa Thavikulwat, Catherine Cukras, Emily Y. Chew, Wai T Wong; A Phase II Trial Evaluating Oral Minocycline in the Treatment of Geographic Atrophy in Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2023;64(8):5058.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : In age-related macular degeneration (AMD), geographic atrophy (GA) development and progression may be triggered by phagocytic innate immune cells, particularly activated outer retinal microglia. Minocycline is an anti-inflammatory agent that inhibits microglial activation. Cell culture and animal models support its neuroprotective role in retinal degeneration. This study represents a phase II trial to evaluate oral minocycline in slowing GA progression.

Methods : In this multi-center, prospective, single-arm, phase II trial, patients with GA secondary to AMD in ≥1 eye were enrolled (National Institutes of Health, Bethesda, MD, and Bristol Eye Hospital, UK). Following a 9-month run-in phase, participants began oral minocycline 100 mg twice/day for 3 years. The primary outcome endpoint was the difference in rate of change of square root GA area on fundus autofluorescence between 24 months of the treatment phase and the 9-month run-in phase, in study eyes, with comparison by linear spline regression. Select exploratory secondary outcomes included differences in rates of change between the two phases in square root GA area on color fundus photography, visual acuity, and central retinal thickness in study eyes. Missing data were assumed missing completely at random.

Results : Of the 37 participants enrolled (mean age 74.3 y, 57% female), 35 initiated treatment. Of these, 21 (60%) completed at least 33 months, while 14 discontinued (7 by request, 6 adverse events/illness, 1 death). Primary and select secondary outcome evaluations showed no significant difference in measures between the two phases (Table). For the primary outcome, the mean difference between enlargement rates during the treatment versus run-in phases was -0.03 mm/year (standard error 0.03; P=0.45). Of the 123 treatment-emergent adverse events reported to date, 46 (37%) were considered related to minocycline (no severe or ocular events), including raised thyroid stimulating hormone (11 participants), skin hyperpigmentation (6 participants), and gastrointestinal symptoms (7 participants).

Conclusions : No anatomic or visual acuity effects were observed in the trial. Oral minocycline may not be beneficial in slowing GA progression. This might relate to suboptimal inhibition of microglia or absence of their causal involvement in GA progression.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

 

Results of Primary and Select Exploratory Secondary Outcomes (Study Eye)

Results of Primary and Select Exploratory Secondary Outcomes (Study Eye)

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