TABLE 1.
Clinical trials on targeted drugs for IgAN.
| Drug name (NCT number) | Drug target | Phase/Status | Inclusion criteria | Intervention/Treatment | Primary outcome measures (Time frame) |
|---|---|---|---|---|---|
| VIS649 (NCT03719443) | Anti-APRIL monoclonal antibody | I/completed | Healthy | VIS649 0.5 mg/kg-20 mg/kg, single dose, IV | Number of participants with TEAE (112 days) Frequency of 12-lead ECG treatment emergent abnormalities (112 days) |
| Blisibimod (NCT02062684) | Anti-BAFF monoclonal antibody | II/III completed | Proteinuria 1–6 g/d | Blisibimod, SC | Proportion of subjects achieving reduction in proteinuria from baseline (24 weeks) |
| Atacicept (NCT02808429) | Recombinant fusion protein against BAFF and APRIL | II/terminated | UPCR 0.75–6 g/gCr | Atacicept 25 mg or 75 mg, once weekly, SC, 72 weeks | Percentage of participants with AEs (96 weeks) |
| Atacicept (NCT04716231 | Recombinant fusion protein against BAFF and APRIL | II/not recruiting | Urine protein excretion ≥1 g/d or UPCR ≥1 g/gCr, eGFR ≥45 ml/min/1.73 m2, SBP ≤150 mmHg and DBP ≤90 mmHg | Atacicept, once weekly, SC | Change from baseline in UPCR (24 weeks) |
| RC18 (NCT04291781) | Recombinant fusion protein against BAFF and APRIL | II/not recruiting | Urine protein excretion ≥1 g/d, eGFR >45 ml/min/1.73 m2 | RC18 160 mg or 240 mg, once weekly, SC, 24 weeks | Change from baseline in 24 h urine protein excretion level (24 weeks) |
| Rituximab (NCT04525729) | Anti-CD20 monoclonal antibody | IV/recruiting | Proteinuria ≥1 g/d, eGFR >30 ml/min/1.73 m2, SBP <130 mmHg, DBP <80 mmHg, Serum albumin >25 g/L | Rituximab 1 g, Day 1 and Day 31, IV | Changes in proteinuria levels over 1 year compared with baseline (1 year) |
| Fostamatinib (NCT02112838) | SYK inhibitor | II/completed | Proteinuria >1 g/d at diagnosis and >0.5 g/d at the second screening visit | Fostamatinib 150 mg or 100 mg, twice daily, by mouth, 24 weeks | Mean change of proteinuria at week 24 (24 weeks) |
| LNP023 (NCT03373461) | Complement factor B inhibitor | II/not recruiting | Urine protein ≥1 g/d at screening and ≥0.75 g/d after the run-in period, eGFR ≥30 ml/min/1.73 m2 | LNP023, twice daily, by mouth | Change from baseline of UPCR (90 days) |
| LNP023 (NCT04557462) | Complement factor B inhibitor | III/not recruiting | EGFR ≥20 ml/min/1.73 m2 | Single arm, LNP023 200 mg, twice daily, by mouth |
Number and percentage of patients with serious AEs, AEs, AEs of special interest, abnormalities in vital signs (Date of first administration to 7 days after the last administration) |
| LNP023 (NCT04578834) | Complement factor B inhibitor | III/recruiting | UPCR ≥1 g/gCr at screening and after the run-in period | LNP023 200 mg, twice daily, by mouth | Ratio to baseline in UPCR at 9 months (9 months) Annualized total eGFR slope over 24 months (24 months) |
| IONIS-FB-LRx (NCT04014335) | Antisense inhibitor of complement factor B | II/recruiting | Hematuria, Proteinuria | Single arm, IONIS-FB-LRx, Weeks 1, 3, 5, and every 4 weeks through Week 25, SC |
Percent reduction in 24 h urine protein excretion (baseline to week 29) |
| APL-2 (NCT03453619) | Complement C3 inhibitor | II/not recruiting | UPCR >0.75 g/gCr, eGFR ≥30 ml/min/1.73 m2 | Single arm, APL-2, once daily, SC, 48 weeks |
Change from baseline of UPCR (48 weeks) |
| OMS721 (NCT03608033) | Humanized anti-MASP-2 monoclonal antibody | III/recruiting | Proteinuria >1 g/d or UPCR >0.75 g/gCr, eGFR ≥30 ml/min/1.73 m2 at screening and baseline | Narsoplimab (OMS721), 12 weeks | Change from baseline in 24 h urine protein excretion at 36 weeks (36 weeks) |
| Ravulizumab (NCT04564339) | Humanized anti-C5 monoclonal antibody | II/recruiting | Proteinuria ≥1 g/d | Ravulizumab, IV, 50 weeks | Percentage change in proteinuria from baseline to week 26 (26 weeks) |
| Cemdisiran (NCT03841448) | Synthetic RNAi targeting complement C5 | II/recruiting | Hematuria, urine protein ≥1 g/d | Cemdisiran (ALN-CC5), SC | Percentage change from baseline in UPCR at week 32 (baseline to week 32) |
| CCX168 (NCT02384317) | C5aR antagonist | II/completed | UPCR >1 g/gCr, eGFR >60 ml/min/1.73 m2 | Single arm, CCX168, twice daily, by mouth, 84 days |
Number of patients with AEs (169 days) |
APRIL, a proliferation-inducing ligand; BAFF, B cell activation factor; TEAE, treatment-emergent adverse events; IV, intravenous infusion; SC, subcutaneous injection; AEs, adverse events; ECG, electrocardiogram; UPCR, urine protein to creatinine ratio; eGFR, estimated glomerular filtration rate; SBP, systolic blood pressure; DBP, diastolic blood pressure; SYK, spleen tyrosine kinase.