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With Aleksandra Rachitskaya, MD; Emmanuel Chang, MD, PhD; Michael Klufas, MD; and Dmitra Skondra, MD

STUDY SUBJECTS

Major Inclusion criteria:

• At least 50 years of age
• Best corrected visual acuity (BCVA) of 24 letters or better
• Diagnosis of GA secondary to AMD confirmed using fundus autofluorescence imaging with GA area size of 2.5 mm2 or more and 17.5 mm2 or less
• Presence of any pattern of hyperautofluorescence in the junctional zone of GA
• At least 1 focal lesion of 1.25 mm2 or more if GA was multifocal

RANDOMIZATION SCHEME AND INTERVENTIONS

Randomized 2:2:1:1 to

• 15 mg pegcetacoplan monthly
• 15 mg pegcetacoplan EOM
• Sham injection monthly
• Sham injection EOM

Primary Endpoint

• Change from baseline to month 12 in the square root of the GA lesion area

Secondary Endpoint

• Change from baseline to month 12 in the following:
  • Untransformed GA lesion area
  • Distance of GA lesion from the fovea (foveal encroachment)
  • BCVA
  • Low-luminance BCVA (LL-BCVA)
  • Low-luminance visual acuity deficit (LL-VD)

Primary Safety Endpoint

• Frequency and severity of treatment-emergent adverse events

Genetic Analysis

• Blood samples were collected for genetic marker analysis and genotyped on the Axiom Precision Medicine Chip

Results

Study population:

• 246 participants; comparable in baseline demographic and ocular characteristics
• Study completion 88.6%

Primary Outcome: Change from baseline to month 12 in the square root of the GA lesion area

• Pegcetacoplan monthly: +.25 mm (29% smaller increase compared to sham)
• Pegcetacoplan EOM: +.28 mm (20% smaller increase compared to sham)
• Pooled sham groups: +.35 mm
• Reductions in growth rate of square root GA lesion area in the pegcetacoplan monthly (45%) and pegcetacoplan EOM (33%) groups compared with sham during months 6-12
• Genetic factors did not significantly affect treatment effect

Secondary Outcomes

• 30% and 20% reductions in untransformed GA lesion area growth at month 12 in the pegcetacoplan monthly and EOM treatment groups, respectively
• No effect of pegcetacoplan on foveal encroachment, visual acuity measures, or LL-VD at month 12 compared with sham treatment

Rescue Treatment

• The proportion of participants who underwent PRP or vitrectomy was lower in the aflibercept groups compared with the control group

Safety

• Injection-related culture-positive endophthalmitis occurred in 2 pegcetacoplan-treated eyes
• Culture-negative endophthalmitis occurred in 1 pegcetacoplan-treated eye
• Higher incidence of choroidal neovascularization (CNV) in eyes treated with pecetacoplan monthly (20.9%) and pegcetacoplan EOM (8.9%) compared to sham (1.2%)
  • Exudative AMD was more common in patients with a history of CNV in the contralateral eye
  • Development of exudative AMD was not associated with any substantial change in visual acuity

Conclusions

• Treatment of GA secondary to AMD with pegcetacoplan reduced GA lesion growth rate by 29% and 20% compared with sham treatment, particularly between months 6-12
• GA growth rate in pegcetacoplan-treated eyes began increasing after cessation of treatment at 12 months, suggesting a need for continuous therapy
• A higher incidence of exudative AMD was observed in eyes treated with pegcetacoplan compared with sham treatment, occurring primarily in patients with a history of contralateral eye CNV, suggesting that pegcetacoplan altered the course of AMD