Table 3.
Clinical trials assessing targeted therapies in IgAN.
| Agent | Mechanism of Action | Registration No. | Phase | Primary Outcome Measures | Trial Results/Status | Reference |
|---|---|---|---|---|---|---|
| Hydroxychloroquine | TLR signaling inhibitor | NCT02942381 | 2 | Proteinuria (every 2 months, total 6 months) | In addition to optimized renin-angiotensin–aldosterone system inhibition, hydroxychloroquine significantly reduced proteinuria without evidence of adverse event | [102] |
| Blisibimod | Monoclonal antibody of soluble and membrane BAFF | NCT02062684 | 2/3 | Proportion of subjects achieving reduction in proteinuria from baseline (24 weeks) | The interim results of blisibimod treatment showed a reduction in the level of proteinuria, peripheral B-cells and immunoglobulins | - |
| VIS649 | Monoclonal IgG2κ antibody targeting APRIL | NCT03719443 | 1 | Number of participants with adverse events and frequency of ECG abnormalities (112 days) | VIS649 treatment reduced serum levels of APRIL, IgA and Gd-IgA1 without evidence of severe adverse event | [109,110] |
| BION-1301 | Monoclonal IgG4 antibody targeting APRIL | NCT03945318 | 1/2 | Incidence and severity of adverse events (76 weeks) | Recruiting | - |
| Atacicept | BAFF/APRIL dual inhibitor | NCT02808429 | 2 | Percentage of adverse events (96 weeks) | 1. Atacicept treatment demonstrated an acceptable safety profile 2. The interim results of atacicept treatment showed early reduction in proteinuria and dose-dependent reduction in Gd-IgA1 | [111] |
| NCT04716231 | 2 | Change from baseline in UPCR (24 weeks) | Active, not recruiting | - | ||
| Telitacicept | BAFF/APRIL dual inhibitor | NCT04291781 | 2 | Change from baseline in 24-h urine protein excretion level (24 weeks) | Results not yet available | - |
| NCT04905212 | 2 | Recruiting | - | |||
| Rituximab | Monoclonal anti-CD20 antibody | NCT00498368 | 4 | Change in proteinuria (12 months) | Rituximab treatment did not significantly improve kidney function or proteinuria and failed to reduce serum levels of Gd-IgA1 and anti-Gd-IgA1 antibodies | [113] |
| Felzartamab | Monoclonal IgG1 antibody targeting CD38 | NCT05065970 | 2 | Relative change in proteinuria value (9 months) |
Recruiting | - |
| Fostamatinib | Spleen tyrosine kinase inhibitor | NCT02112838 | 2 | Mean change from baseline in proteinuria (24 weeks) | Fostamatinib treatment did not significantly improve proteinuria or eGFR | [121] |
| NEFECON (TARPEYO) | Distal ileum targeted-release budesonide formulation targeting B-cells in mucosal lymphoid tissue | NCT01738035 | 2 | Change from baseline in UPCR (9 months) | Nefecon treatment reduced proteinuria and preserved kidney function | [132] |
| NCT03643965 | 3 | Change in proteinuria (9 months) and eGFR (up to 2 years) | [131] | |||
| CCX168 | Anti-C5a receptor antagonist | NCT02384317 | 2 | The number of patients with adverse events (169 days) | CCX168 treatment improved proteinuria | [142] |
| ALXN1210 | Long-acting C5-blocking antibody | NCT04564339 | 2 | Percentage change from baseline in proteinuria (26 weeks) | Recruiting | - |
| ALN-CC5 | Small interfering RNA targeting C5 | NCT03841448 | 2 | Percentage change from baseline in UPCR (32 weeks) | Active, not recruiting | - |
| APL-2 | Cyclic peptide inhibitor of C3 | NCT03453619 | 2 | Proteinuria (48 weeks) | Active, not recruiting | - |
| LNP023 | Selective complement factor B inhibitor | NCT03373461 | 2 | Multiple comparison procedure modeling estimates of the ratio to baseline of UPCR (90 days) | LNP023 treatment led to continuous reduction in proteinuria and strong inhibition of alternative pathway activity | [143] |
| NCT04578834 | 3 | Ratio to baseline in UPCR (9 months) and annualized total eGFR slope (24 months) | Recruiting | - | ||
| IONIS-FB-LRx | Antisense inhibitor of complement factor B | NCT04014335 | 2 | Percent reduction in 24-h urine protein excretion (29 weeks) | Recruiting | - |
| OMS721 | Monoclonal antibody against mannan-associated lectin-binding serine protease-2 | NCT02682407 | 2 | Proportion of adverse events (Up to 104 weeks) and change from baseline in serum and urine complement component levels (38 weeks) | OMS721 treatment reduced proteinuria and preserved kidney function | [144] |
| NCT03608033 | 3 | Change from baseline in 24-h urine protein excretion (36 weeks) | Recruiting | - |
UPCR: urine protein to creatinine ratio.