Table 1.
Summary of complement inhibitors in clinical trials for dry AMD.
| Target | Drug (sponsor) | Administration | Phase | Design | Sample size (n=) | Primary outcome measure | Status | First posted | Trial number | Clinical outcome |
|---|---|---|---|---|---|---|---|---|---|---|
| POT-4 (Alcon) | Intravitreal | II | Monthly vs. sham | 10 | GA area change at month 12 by FAF | Terminated | 2012 | NCT01603043 | Drug deposit formation | |
| APL-2 (Apellis) | Intravitreal | II | Monthly vs. EOM vs. sham | 246 | Square root of GA area change at 12 months | Completed | 2015 | NCT02503332 | 29% reduction in GA lesion growth | |
| C3 | APL-2 (Apellis) | Intravitreal | III | Monthly vs. EOM vs. sham | 600 (estimated) | GA area change at month 12 by FAF | Ongoing | 2018 | NCT03525613 | — |
| APL-2 (Apellis) | Intravitreal | III | Monthly vs. EOM vs. sham | 1200 (estimated) | Percentage of adverse events at month 36 | Ongoing | 2021 | NCT03777332 | — | |
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| NGM621 (NGM bio.) | Intravitreal | II | Every 4 weeks vs. 8 weeks vs. sham | 240 (estimated) | GA area change at week 48 by FAF | Ongoing | 2020 | NCT04465955 | — | |
| Eculizumab (Alexion) | Intravenous | II | Low dose vs. high dose | 60 | Growth of GA and decrease in drusen volume | Completed | 2009 | NCT00935883 | Lack of efficacy | |
| LFG316 (Novartis) | Intravitreal | I | SAD | 24 | Safety and tolerability | Completed | 2010 | NCT01255462 | Safe and well-tolerated | |
| LFG316 (Novartis) | Intravitreal | II | Low dose vs. high dose vs. sham | 158 | GA area change at day 505 by FAF | Completed | 2012 | NCT01527500 | Lack of efficacy | |
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| C5 | ARC1905 (Ophthotech) | Intravitreal | I | Low dose vs. high dose | 47 | Safety and tolerability | Completed | 2009 | NCT00950638 | Safe and well-tolerated |
| ARC1905 (Ophthotech) | Intravitreal | II/III | Low dose vs. high dose vs. sham | 286 | GA area change at month 12 by FAF | Completed | 2016 | NCT02686658 | 27% reduction in GA lesion growth | |
| ARC1905 (Ophthotech) | Intravitreal | III | Monthly vs. EOM vs. sham | 400 (estimated) | Mean rate of GA change at month 12 by FAF | Ongoing | 2020 | NCT04435366 | — | |
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| Lampalizumab (Roche) | Intravitreal | Ia | SAD | 18 | Safety and tolerability | Completed | 2009 | NCT00973011 | Safe and well-tolerated | |
| FD | Lampalizumab (Roche) | Intravitreal | II | Every 2 weeks vs. 4 weeks vs. sham | 96 | GA area change at week 24 by FAF | Completed | 2014 | NCT02288559 | 20% reduction in GA lesion area |
|
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| Lampalizumab (Roche) | Intravitreal | II | Monthly vs. EOM vs. sham | 159 | Percentage of adverse events | Terminated | 2012 |
NCT01229215
NCT01602120 |
Lack of efficacy | |
| FD | Lampalizumab (Roche) | Intravitreal | III | Every 4 weeks vs. 6 weeks vs. sham | 906 | GA area change at week 48 by FAF | Terminated | 2014 |
NCT02247479
NCT02247531 |
Lack of efficacy |
| Lampalizumab (Roche) | Intravitreal | III | Every 4 weeks vs. every 6 weeks | 994 | Percentage of adverse events at week 96 | Terminated | 2016 | NCT02745119 | Lack of efficacy | |
|
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| CLG561 (Novartis) | Intravitreal | I | SAD (5 dose levels) | 50 | Safety and tolerability | Completed | 2013 | NCT01835015 | Safe and well-tolerated | |
| Properdin | CLG561 (Novartis) | Intravitreal | II | CLG561 vs. CLG561+LFG316 vs. sham | 114 | Percentage of adverse events, GA area change at day 337 by FAF | Completed | 2015 | NCT02515942 | Lack of efficacy |
|
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| FB | IONIS-FB-LRx (Lonis) | Subcutaneous | II | IONIS-FB-LRx vs. placebo | 330 (estimated) | GA area change at week 49 by retinal imaging | Ongoing | 2019 | NCT03815825 | — |
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| AAVCAGsCD59 (Hemera) | Intravitreal | I | SAD (3 dose levels) | 17 | Percentage of adverse events at week 26 | Completed | 2017 | NCT03144999 | Safe and well-tolerated | |
| CD59 | AAVCAGsCD59 (Hemera) | Intravitreal | II | Low dose vs. high dose vs. sham | 132 (estimated) | GA area change at month 24 by FAF | Ongoing | 2020 | NCT04358471 | — |
|
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| GT005 (gyroscope) | Subretinal | I/II | SAD (3 dose levels) | 45 (estimated) | Percentage of adverse events at week 48 | Ongoing | 2019 | NCT03846193 | — | |
| FI | GT005 (gyroscope) | Subretinal | II | Low dose vs. high dose vs. sham | 180 (estimated) | GA area change at week 48 by FAF | Ongoing | 2020 |
NCT04437368
NCT04566445 |
— |
|
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| FH | GEM103 (Gemini) | Intravitreal | I | SAD (4 dose levels) | 12 | Safety and tolerability | Completed | 2020 | NCT04246866 | Safe and well-tolerated |
| GEM103 (Gemini) | Intravitreal | II | GEM103 vs. sham | 45 (estimated) | Percentage of adverse events at month 18 | Ongoing | 2020 | NCT04643886 | — | |
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| C1q | ANX007 (Annexon) | Intravitreal | II | Monthly vs. EOM vs. sham | 240 (estimated) | GA area change at month 12 by FAF | Ongoing | 2020 | NCT04656561 | — |
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.