Table 2:
Summary of clinical trials with complement inhibitors in IgAN.
| Agent | Target/mechanism of action | Compound/route | Company | Trial registration no./trial name | Phase | Design | Primary outcome | Results/status |
|---|---|---|---|---|---|---|---|---|
| Narsoplimab (OMS721) |
MASP-2/LP inhibition | Monoclonal antibody against MASP-2/intravenous injection | Omeros | NCT02682407 | 2 | Substudy 1: single-arm open-label study | Safety and tolerability | - Safe and well tolerated |
| Substudy 2: RCT followed by open-label | - Proteinuria reduction with preserved eGFR | |||||||
| NCT03608033/ARTEMIS-IGAN | 3 | Randomized, double-blind, placebo-controlled | Change of proteinuria from baseline at 36 weeks | Ongoing | ||||
| Iptacopan (LNP023) | Factor B/AP inhibition | Small molecule/orally administered | Novartis | NCT03373461 | 2 | Randomized, double-blind, dose-ranging, parallel-group adaptive design | Safety and tolerability | - Well tolerated |
| - Reduction in proteinuria | ||||||||
| - Strong inhibition of alternative pathway | ||||||||
| NCT04578834/APPLAUSE-IgAN | 3 | Multi-center, randomized, double-blind, placebo-controlled | Ratio to baseline in UPCR (9 months) and annualized total eGFR slope (24 months) |
Ongoing | ||||
| IONIS-FB-LRX (RG6299) |
Factor B/antisense inhibitor of complement factor B | Oligonucleotide/subcutaneous injection | Ionis | NCT04014335 | 2 | Single-arm, open-label study | Change of proteinuria from baseline at 29 weeks | Ongoing |
| Pegectacoplan (APL-2) | C3/AP inhibition | Pegylated peptide/subcutaneous injection | Apellis | NCT03453619 | 2 | Single-arm, open-label study | Safety and efficacy in reduction of proteinuria at Week 48 | Ongoing |
| Pelecopan (BCX9930) |
Factor D/AP inhibition | Small molecule/orally administered | BioCryst Pharmaceuticals | NCT05162066 | 2 | Open-label, proof-of-concept study | Safety and tolerability | Terminated, no results available |
| Percent change from baseline in UPCR | ||||||||
| Vemircopan (ALXN2050) |
Factor D/AP inhibition | Small molecule/orally administered | Alexion | NCT05097989 | 2 | Randomized, double-blind, placebo-controlled study | Percentage proteinuria change at Week 26 | Ongoing |
| Ravulizumab (ALXN1210) |
C5/TP inhibition | Monoclonal antibody/intravenous injection | Alexion/AstraZeneca | NCT04564339 | 2 | Randomized, double-blind, placebo-controlled study | Percentage proteinuria change at Week 26 | Ongoing |
| Cemdisiran (ALN-CC5) | C5/TP inhibition | Small interfering RNA/subcutaneous injection | Alnylam | NCT03841448 | 2 | Randomized, double-blind, placebo-controlled study | Percentage proteinuria change at Week 32 | Ongoing |
| Avacopan (CCX168) |
C5aR1/inhibition of anaphylatoxin | Small molecule/orally administered | Chemocentryx | NCT02384317 | 2 | Single-arm open-label study | Change in slope of the UPCR from the 8-week run-in period through the 12 weeks | Improvement in UPCR slope, with ∼50% improvement in 3/7 patients |
eGFR: estimated glomerular filtration rate; MASP-2: Mannan-associated lectin-binding serine protease-2; RCT: randomized controlled trial; UPCR: urinary protein-to-creatinine ratio.