C5 Inhibitor Avacincaptad Pegol for Geographic Atrophy Due to Age-Related Macular Degeneration: A Randomized Pivotal Phase 2/3 Trial
NCT02686658 | GATHER1 | Jaffe GJ et al. (2021)
Jaffe, G. J., Westby, K., Csaky, K. G., Monés, J., Pearlman, J. A., Patel, S. S., Joondeph, B. C., Randolph, J., Masonson, H., & Rezaei, K. A. C5 Inhibitor Avacincaptad Pegol for Geographic Atrophy Due to Age-Related Macular Degeneration: A Randomized Pivotal Phase 2/3 Trial. Ophthalmology, 2021; 128:576-586.
Locations
63 sites across the United States, Europe, and Israel
Study Period
January 2016 – October 2018
Study Design
International, prospective, randomized, double-masked, sham-controlled pivotal phase 2/3 trial
Study Population
Experimental Group
Control Group
Follow-up Time: 12 months
Outcomes
Durability
Not reported
Vision
Best-Corrected Visual Acuity (BCVA)
Mean BCVA change from baseline to12 months:
• 2 mg = -7.9 letters (SE 2.66); Sham = -9.3 letters (SE 2.59); difference = +1.4 letters
• 4 mg = -3.8 letters (SE 3.1); Sham = -3.5 letters (SE 3.0); difference = -0.3 letters
Other
Efficacy: Progression Outcomes
Geographic Atrophy (GA) Growth (Primary Outcomes)
The least squares mean change in the square root GA lesion area from baseline to month 12:
• 0.292 mm (avacincaptad pegol 2mg) vs. 0.402 mm (the)
• 0.321 mm (avacincaptad pegol 4 mg) vs. 0.444 mm (the corresponding sham
The reduction in the mean GA growth rate over 12 months (Primary Outcome):
• 2 mg compared with the corresponding sham = 27.4% (0.110 mm reduction, p = 0.0072)
• 4 mg compared with the corresponding sham = 27.8% (0.124 mm reduction, p = 0.0051)
The impact of avacincaptad pegol treatment on GA growth at Month 6:
• 2 mg compared with the corresponding sham = 28.4% reduction
• 4 mg compared with the corresponding sham = 26.6% reduction for
Untransformed (without square root transformation) reduction in the mean GA growth rate from baseline to 12 months:
• 2 mg compared with the corresponding sham = 30.5%
• 4 mg compared with the corresponding sham = 25.6%
Immunognicity
Not reported
Pharmokinetics
Not reported
Anatomic
Not reported
Safety
Treatment-emergent AEs (TEAEs)
Ocular TEAEs in the study eye:
• 2 mg = 35 (52.2%)
• 4 mg = 57 (68.7%)
• Sham = 38 (34.5%)
Ocular TEAEs in the contralateral eye
• 2 mg = 10 (14.9%)
• 4 mg = 17 (20.5%)
• Sham = 20 (18.2%)
Systemic TEAEs:
• 2 mg = 39 (58.2%)
• 4 mg = 47 (56.6%)
• Sham = 60 (54.5%)
Serious AEs (SAEs
No serious ocular AEs or endophthalmitis.
Systemic SAEs:
• 2 mg = 7 (10.4%)
• 4 mg = 17 (20.5%)
• Sham = 20 (18.2%)
Conclusion
Avacincaptad pegol significantly reduced GA growth at both 2 mg and 4 mg doses over 12 months, with a favorable safety profile.
Risk of Bias Assessment for Primary Outcome
Randomization Process
Low risk
Note: “A web-based randomization system (ID-net, IDDI, Louvain-la-Neuve, Belgium) was used…”, “Baseline characteristics were balanced between various study groups.”
Missing Outcome Data
Low risk
Note: Evidence that the result was not biased by missing outcome data (sensitivity analysis): “Four simple sensitivity analyses described by Miller et al. were performed...”
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. “All efficacy analyses were conducted for the intention-to-treat population.”
Measurement of the Outcome
Low risk Note: “Masked Readers (Duke Reading Center) independently analyzed and graded the images.” “If there was more than a 10% discrepancy in the measurements, the results were arbitrated by the Reading Center Director (G.J.J.).”
Overall
Low risk
Categories: Dry AMD Geographic Atrophy