Gildeuretinol Acetate versus Placebo for Geographic Atrophy Secondary to Age-Related Macular Degeneration: The Study...

To assess the effects of gildeuretinol acetate (C20D3-vitamin A) in geographic atrophy (GA).

A 24-month, double-masked, multicenter, randomized, placebo-controlled trial.

Participants aged ≥60 years with GA.

Randomized 2:1 to oral gildeuretinol acetate 14 mg daily or placebo.

The primary endpoint was GA growth rate from baseline to 24 months. A prespecified sensitivity analysis accounted for a 6-month delay in onset of therapeutic effect. Secondary endpoints included change from baseline in low-luminance visual acuity (LLVA), best-corrected visual acuity (BCVA), Visual Function Questionnaire-25, and Functional Reading Independence (FRI) Index.

Among 198 randomized participants (mean [standard deviation {SD}] age, 78.4 [7.0] years; 68.7% women), 69.2% completed the 24-month study. In the gildeuretinol and placebo groups, baseline mean (SD) total GA lesion area in mm² was 7.72 (6.10) and 7.09 (4.16); BCVA letter scores were 56.2 (21.3) (Snellen equivalent: ∼20/80) and 58.8 (18.0) (∼20/70); and LLVA letter scores were 31.1 (19.0) (∼20/200) and 31.6 (17.8) (∼20/250), respectively. Mean GA growth rates were 1.62 mm²/yr with gildeuretinol and 1.87 mm²/yr with placebo (least squares [LSs] mean difference: -0.25 mm²/yr; 95% confidence interval [CI]: -0.53 to 0.03; P = 0.075), a 13.4% relative reduction for gildeuretinol versus placebo. The LS mean (standard error) GA growth rates from 6 to 24 months were 1.90 (0.12) mm²/yr (placebo) and 1.61 (0.08) mm²/yr (gildeuretinol), a 15.3% relative reduction (-0.29 mm²/yr; 95% CI: -0.576 to -0.004; nominal P = 0.047). At 24 months, LLVA declined 3.9 and 8.3 ETDRS letters in the gildeuretinol and placebo groups, respectively (difference: 4.4 letters; 95% CI: 0.40-8.41; nominal P = 0.031). Best-corrected visual acuity declined 6.9 letters with gildeuretinol and 10.2 letters with placebo (difference: 3.3 letters; 95% CI: -0.63 to 7.23; P = 0.099). Visual Function Questionnaire-25 scores declined 4.81 fewer points with gildeuretinol than placebo (95% CI: 0.87-8.76; nominal P = 0.017), and FRI scores declined 0.35 fewer points (95% CI: 0.11-0.58; nominal P = 0.004).

The prespecified primary endpoint was not met. Prespecified piecewise and secondary functional and patient-reported analyses favored gildeuretinol with nominal P values; these exploratory findings support further evaluation in adequately powered trials.

NCT03845582.

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