A randomized, open-label, multicenter study of switching to brolucizumab with or without a loading dose for patients with suboptimal anatomically controlled neovascular age-related macular degeneration-the FALCON study

Graefes Arch Clin Exp Ophthalmol. 2022 Aug;260(8):2695-2702. doi: 10.1007/s00417-022-05591-z. Epub 2022 Feb 21.

Abstract

Background: Treatment initiation with brolucizumab, a new potent anti-vascular endothelial growth factor (VEGF) agent, is typically performed with three monthly injections (loading dose) and has been well studied in treatment-naïve patients. However, no clinical data are available yet on whether or not anti-VEGF pretreated patients also benefit from a loading dose. In the clinical setting, different heterogeneous treatment patterns are used as no clinical trial has addressed this so far in a head-to-head comparison. Therefore, the FALCON study is investigating whether patients with unsatisfactory response to previous anti-VEGF treatments benefit from a loading dose at the switch to brolucizumab treatment.

Methods: FALCON is a 52-week, two-arm, randomized, open-label, multicenter, multinational study in patients with residually active neovascular age-related macular degeneration (nAMD) who will be randomized 1:1 and started with brolucizumab 6 mg loading (three monthly loading doses) or brolucizumab 6 mg non-loading (one initial injection) and consecutive treatment every 12 weeks, respectively. The primary objective is to demonstrate non-inferiority of the non-loading vs. loading arm in mean change of best-corrected visual acuity (BCVA) from baseline to the mean value at week 40 to week 52. Secondary objectives include the assessment of anatomical outcomes, treatment intervals, safety and tolerability.

Results: FALCON will be the first study to assess treatment initiation with an anti-VEGF agent in a switch situation with or without loading dose in patients with nAMD.

Conclusions: The results will support the optimization of treatment of patients with previous unsatisfactory anti-VEGF response. Therefore, we expect to see an impact on current clinical practice which has been established for more than a decade.

Trial registration: Clinicaltrials.gov: NCT04679935, date of registration-22-Dec 2020; EUDRACT number: 2019-004763-53, date of registration-03 Dec 2019.

Keywords: Anti-VEGF; Brolucizumab; Neovascular age-related macular degeneration; Switch.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Humans
  • Infant, Newborn
  • Intravitreal Injections
  • Macular Degeneration* / drug therapy
  • Receptors, Vascular Endothelial Growth Factor
  • Recombinant Fusion Proteins / therapeutic use
  • Treatment Outcome
  • Visual Acuity
  • Wet Macular Degeneration* / diagnosis
  • Wet Macular Degeneration* / drug therapy

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Recombinant Fusion Proteins
  • Receptors, Vascular Endothelial Growth Factor
  • brolucizumab

Associated data

  • ClinicalTrials.gov/NCT04679935