Review Article

Complement Inhibitors in Age-Related Macular Degeneration: A Potential Therapeutic Option

Table 1

Summary of complement inhibitors in clinical trials for dry AMD.

TargetDrug (sponsor)AdministrationPhaseDesignSample size (=)Primary outcome measureStatusFirst postedTrial numberClinical outcome

POT-4 (Alcon)IntravitrealIIMonthly vs. sham10GA area change at month 12 by FAFTerminated2012NCT01603043Drug deposit formation
APL-2 (Apellis)IntravitrealIIMonthly vs. EOM vs. sham246Square root of GA area change at 12 monthsCompleted2015NCT0250333229% reduction in GA lesion growth
C3APL-2 (Apellis)IntravitrealIIIMonthly vs. EOM vs. sham600 (estimated)GA area change at month 12 by FAFOngoing2018NCT03525613
APL-2 (Apellis)IntravitrealIIIMonthly vs. EOM vs. sham1200 (estimated)Percentage of adverse events at month 36Ongoing2021NCT03777332

NGM621 (NGM bio.)IntravitrealIIEvery 4 weeks vs. 8 weeks vs. sham240 (estimated)GA area change at week 48 by FAFOngoing2020NCT04465955
Eculizumab (Alexion)IntravenousIILow dose vs. high dose60Growth of GA and decrease in drusen volumeCompleted2009NCT00935883Lack of efficacy
LFG316 (Novartis)IntravitrealISAD24Safety and tolerabilityCompleted2010NCT01255462Safe and well-tolerated
LFG316 (Novartis)IntravitrealIILow dose vs. high dose vs. sham158GA area change at day 505 by FAFCompleted2012NCT01527500Lack of efficacy

C5ARC1905 (Ophthotech)IntravitrealILow dose vs. high dose47Safety and tolerabilityCompleted2009NCT00950638Safe and well-tolerated
ARC1905 (Ophthotech)IntravitrealII/IIILow dose vs. high dose vs. sham286GA area change at month 12 by FAFCompleted2016NCT0268665827% reduction in GA lesion growth
ARC1905 (Ophthotech)IntravitrealIIIMonthly vs. EOM vs. sham400 (estimated)Mean rate of GA change at month 12 by FAFOngoing2020NCT04435366

Lampalizumab (Roche)IntravitrealIaSAD18Safety and tolerabilityCompleted2009NCT00973011Safe and well-tolerated
FDLampalizumab (Roche)IntravitrealIIEvery 2 weeks vs. 4 weeks vs. sham96GA area change at week 24 by FAFCompleted2014NCT0228855920% reduction in GA lesion area

Lampalizumab (Roche)IntravitrealIIMonthly vs. EOM vs. sham159Percentage of adverse eventsTerminated2012NCT01229215
NCT01602120
Lack of efficacy
FDLampalizumab (Roche)IntravitrealIIIEvery 4 weeks vs. 6 weeks vs. sham906GA area change at week 48 by FAFTerminated2014NCT02247479
NCT02247531
Lack of efficacy
Lampalizumab (Roche)IntravitrealIIIEvery 4 weeks vs. every 6 weeks994Percentage of adverse events at week 96Terminated2016NCT02745119Lack of efficacy

CLG561 (Novartis)IntravitrealISAD (5 dose levels)50Safety and tolerabilityCompleted2013NCT01835015Safe and well-tolerated
ProperdinCLG561 (Novartis)IntravitrealIICLG561 vs. CLG561+LFG316 vs. sham114Percentage of adverse events, GA area change at day 337 by FAFCompleted2015NCT02515942Lack of efficacy

FBIONIS-FB-LRx (Lonis)SubcutaneousIIIONIS-FB-LRx vs. placebo330 (estimated)GA area change at week 49 by retinal imagingOngoing2019NCT03815825

AAVCAGsCD59 (Hemera)IntravitrealISAD (3 dose levels)17Percentage of adverse events at week 26Completed2017NCT03144999Safe and well-tolerated
CD59AAVCAGsCD59 (Hemera)IntravitrealIILow dose vs. high dose vs. sham132 (estimated)GA area change at month 24 by FAFOngoing2020NCT04358471

GT005 (gyroscope)SubretinalI/IISAD (3 dose levels)45 (estimated)Percentage of adverse events at week 48Ongoing2019NCT03846193
FIGT005 (gyroscope)SubretinalIILow dose vs. high dose vs. sham180 (estimated)GA area change at week 48 by FAFOngoing2020NCT04437368
NCT04566445

FHGEM103 (Gemini)IntravitrealISAD (4 dose levels)12Safety and tolerabilityCompleted2020NCT04246866Safe and well-tolerated
GEM103 (Gemini)IntravitrealIIGEM103 vs. sham45 (estimated)Percentage of adverse events at month 18Ongoing2020NCT04643886

C1qANX007 (Annexon)IntravitrealIIMonthly vs. EOM vs. sham240 (estimated)GA area change at month 12 by FAFOngoing2020NCT04656561

FD: factor D; FB: factor B; FI: factor I; FH: factor H; EOM: every other month; SAD: single ascending dose; GA: geographic atrophy; FAF: fundus autofluorescence.