Characterizing New-Onset Exudation in the Randomized Phase 2 FILLY Trial of Complement Inhibitor Pegcetacoplan for Geographic Atrophy
NCT02503332 | FILLY | Wykoff et al. (2021)
Wykoff, C. C., Rosenfeld, P. J., Waheed, N. K., Singh, R. P., Ronca, N., Slakter, J. S., Staurenghi, G., Monés, J., Baumal, C. R., Saroj, N., Metlapally, R., Ribeiro, R. Characterizing New-Onset Exudation in the Randomized Phase 2 FILLY Trial of Complement Inhibitor Pegcetacoplan for Geographic Atrophy. Ophthalmology, 2021; 128:1325-1336.
Locations
46 sites across the United States, Australia, and New Zealand
Study Period
Not reported
Study Design
Post hoc analysis of a phase 2, prospective, randomized, single-masked, sham-controlled trial
Study Population
Experimental Group
Control Group
Follow-up Time: 18 months
Outcomes
Durability
Not reported
Vision
Best-Corrected Visual Acuity (BCVA) BCVA change at eAMD diagnosis:
• Mean = -2.3 lettersBCVA change from baseline to Month 18:
• eAMD eyes = -11 letters
• non-eAMD eyes = -6 letters.
Other
Efficacy: Progression OutcomesExudative AMD (eAMD) New-Onset eAMD incidence over 18 months (Primary Outcome):
• Pegcetacoplan Monthly = 20.9% (18/86)
• Pegcetacoplan EOM = 8.9% (7/79)
• Sham = 1.2% (1/81)Mean time to eAMD diagnosis = 256 days (range: 31-555 days) for all three groups.Baseline history of eAMD in the fellow eye (risk factor of the new onset eAMD in the study eye):
• Patients with new development of eAMD = 69% (18/26)
• Patients without new development of eAMD = 35% (76/217)
• p = 0.0007Double-layer sign (DLS) in the study eye (risk factor of the new onset eAMD in the study eye):
• Patients with new development of eAMD = 73.1% (19/26)
• Patients without new development of eAMD = 32.5% (70/215)
• p < 0.0001
Immunognicity
Not reported
Pharmokinetics
Not reported
Anatomic
Macular Neovascularization (MNV) Fluorescein Angiography (FA) Findings:
• FA confirmed MNV in 10/17 eyes (59%) at eAMD diagnosis, all classified as occult lesions.
• No FA evidence of MNV in 7/17 eyesOthers For patients with new eAMD:
• Mean increase in central retinal thickness (CRT) = 60 µm
• Cystoid spaces detected in 76% of affected eyes
• Subretinal fluid detected in 62% of affected eyes
Safety
Not specifically reported for this post hoc analysis.
Conclusion
Pegcetacoplan treatment slowed GA progression but was associated with an increased incidence of investigator-determined exudative AMD. The presence of fellow-eye eAMD and baseline double-layer sign were significant risk factors. The safety profile was acceptable, supporting the continuation of phase 3 trials.
Risk of Bias Assessment for Primary Outcome
Randomization Process
Low risk
Note: *“Randomization was performed using a web-based system, and the randomization schedule was blocked to ensure balanced treatment allocations within sites.” *“The pegcetacoplan and sham groups were comparable with regard to baseline demographic and ocular characteristics”
Missing Outcome Data
Low risk
Note: This is a post hoc analysis, the patients without needed information were excluded from the final analysis. Therefore, the missingness did not depend on the true value.
Selection of the Reported Results
Low risk Note: have registration with protocol.
Deviations from Intended Observations
Low risk Note: This is a double-masked study. mITT was applied to the primary outcome analysis.
Measurement of the Outcome
Low risk Note: This is double masked study. In addition, *“…Images were assessed by the central reading center.”
Overall
Low risk
Categories: Dry AMD Geographic Atrophy