Impact of Baseline Characteristics on Geographic Atrophy Progression in the FILLY Trial Evaluating the Complement C3 Inhibitor Pegcetacoplan

NCT02503332 | FILLY | Steinle NC et al. (2021)

Steinle, N. C., Pearce, I., Monés, J., Metlapally, R., Saroj, N., Hamdani, M., Ribeiro, R., Rosenfeld, P. J., & Lad, E. M. Impact of Baseline Characteristics on Geographic Atrophy Progression in the FILLY Trial Evaluating the Complement C3 Inhibitor Pegcetacoplan. Am J Ophthalmol, 2021; 227:116–124.

Locations

Multicenter international study

Study Period

Not reported

Study Design

Post hoc analysis of a Phase 2, multicenter, randomized, single-masked, sham-controlled trial

Study Population

Characteristic:

Type of AMD:

1 (Dry AMD)

AMD Stage:

3 (Late)

Total Sample Size:

246 randomized, 176 for final analysis

Age:

Post hoc analysis of a Phase 2, multicenter, randomized, single-masked, sham-controlled trial

Sex (Male) n%:

Not reported

Experimental Group

Intervention Therapy:

Pegcetacoplan 15 mg

Dose & Frequency:

Intravitreal injection monthly or every other month (EOM) for 12 months

Age (Years):

• Monthly=79.6±7.51 • EOM=80.9±7.55

Number of Patients:

• Monthly = 86 • EOM = 79

Male N %:

• Monthly=31 (36.0%) • EOM=29 (36.7%)

Patients Followed Up:

• Monthly = 62 • EOM = 53

Control Group

Intervention Therapy:

Sham injection

Dose & Frequency:

Monthly or EOM for 12 months

Age (Years):

78.4±7.43

Number of Patients:

Patients Followed Up:

Follow-up Time: 12 months

Outcomes

Durability

Not reported

Vision

Not reported

Other

Efficacy: Progression Outcomes
Geographic Atrophy (GA)
Overall mean change in GA lesion size from baseline to Month 12:
• Pegcetacoplan Monthly = 0.26 mm (SD 0.17)
• Pegcetacoplan EOM = 0.27 mm (SD 0.26)
• Sham = 0.36 mm (SD 0.21)
Compared to sham:
• Monthly dosing (p <0.05)
• EOM dosing (p <0.05).

Risk Factors for GA Progression (multiple variate analysis)
• Patients with extrafoveal GA lesions showed significantly higher lesion growth compared to foveal lesions (p =0.001)
• Larger low-luminance deficit (LLD) at baseline was associated with increased GA lesion growth (p = 0.023)
• Pegcetacoplan treatment significantly reduced GA progression in all subgroups, even when accounting for these risk factors.

Immunognicity

Not reported

Pharmokinetics

Not reported

Anatomic

Not reported

Safety

Not reported

Outcomes

Conclusion

Pegcetacoplan significantly reduced GA progression at both monthly and EOM doses over 12 months, even after adjusting for baseline risk factors.

Risk of Bias Assessment for Primary Outcome

Randomization Process

Some concerns

Note: “Randomization was performed using a web-based system, and the randomization schedule was blocked to ensure balanced treatment allocations within sites.”
However, as this is a post hoc analysis, the patients without needed information were excluded from the final analysis.

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

Some concerns