Design Characteristics of Geographic Atrophy Treatment Trials: Systematic Review of Registered Trials in ClinicalTrials.gov

Purpose Currently there is no effective treatment for geographic atrophy (GA) secondary to age-related macular degeneration, despite many trials that were completed or are ongoing. The purpose of this systematic review is to describe the key design characteristics of GA trials. Well-designed GA trials using appropriate outcome measures are critical for the discovery of an effective treatment. This review may provide valuable insights for improving the design of future trials. Methods Two reviewers independently searched for eligible trials (last search on February 28, 2017) and abstracted data of design characteristics including eligibility criteria, sample size, length of follow-up, and primary and secondary outcomes. Results Among 53 registered GA treatment trials, 10 (19%) were in phase 1, 36 (68%) in phase 1–2 or 2 (phase 2), and 7 (13%) in phase 2–3 or 3 (phase 3); 24 of the 53 trials (45%) are ongoing. The most common interventions were anti-inflammatory agents (40%). GA growth was used as the primary outcome in 58% of phase 2 trials and 71% of phase 3 trials, and as a secondary outcome in 31% of phase 2 trials and 0% of phase 3 trials. Visual acuity (VA) was used as the primary outcome in 17% of phase 2 trials and 14% of phase 3 trials, and as a secondary outcome in 67% of phase 2 trials and 57% of phase 3 trials. The median sample size of trials was 22 in phase 1, 60 in phase 2, and 772 in phase 3, with median follow-up length of 0.7, 1.0, and 2.0 years, respectively. The study eye baseline VA criterion was specified in 33 trials (62%) and varied across trials, with a lower limit of 20/50 to 20/400. The criterion for baseline GA size was specified in 14 trials (26%), with minimum GA size 0.5 to 1 disc area. Conclusions There exists large variation in the design characteristics of GA treatment trials. GA growth is the most common primary outcome measure, and VA is the most common secondary outcome measure. Future trials should consider these design characteristics to advance the discovery of an effective treatment for GA.