Effectiveness of a lighter versus standard initial dosing regimen of Faricimab in Patients with Pretreated Neovascular Age-Related Macular Degeneration: Protocol of a Multicentre Randomised Controlled Phase III Non-Inferiority Clinical Trial

Purpose To evaluate whether initiating faricimab without an induction (“loading”) phase (Light Touch regimen) is non-inferior to standard induction therapy in terms of visual outcomes in patients with neovascular age-related macular degeneration (nAMD) previously treated with other anti-angiogenic agents. Methods This multicentre, phase III, parallel-group randomised controlled non-inferiority trial is recruiting patients with nAMD unable to maintain disease control beyond 4–12-week treatment intervals from up to 16 UK NHS retinal centres. Participants are randomised 1:1 to receive either three monthly faricimab injections (standard induction) followed by treat-and-extend or immediate treat-and-extend matching their pre-switch interval (Light Touch Regimen). The primary outcome is mean change in best-corrected visual acuity from baseline to average of Weeks 52 and 56, measured by ETDRS letter score. Secondary outcomes include anatomical measures on optical coherence tomography, treatment frequency, patient-reported outcomes, and safety endpoints. Randomisation uses minimisation by baseline visual acuity, pre-switch interval, and site. Visual acuity assessors remain masked to treatment allocation. A sample size of 230 patients provides 90% power to demonstrate non-inferiority with a pre-specified margin. Conclusions This is the first prospective randomised trial comparing interval-matched versus standard induction dosing when switching to faricimab in pretreated nAMD. Results will provide evidence-based guidance on optimal switching protocols, with potential implications on assessment of treatment burden and healthcare resource utilization. If non-inferiority is demonstrated, the light touch approach could reduce patient visits while maintaining visual outcomes. Trial Registration ISRCTN10012824