Table 2.
Clinical trials of novel medications in IgAN.
| Trial (NCT number) | Intervention | Mechanism of intervention | Inclusion criteria | Exclusion criteria | Trial design; status |
Primary end point (results) | Follow-up duration |
|---|---|---|---|---|---|---|---|
| Glucocorticoids | |||||||
| NefIgArd (NCT03643965) | Nefecon 16 mg once daily by mouth for 9 months vs. matching placebo | A modified-release formulation of budesonide that targets the sites of mucosal B-cell induction | Proteinuria ≥ 1 gm/day Stabilized on RAAS-i at the maximum tolerated dose according to 2012 KDIGO guidelines eGFR 35–90 mL/min/1.73 m2 in using CKD-EPI equation |
Acute or chronic infectious disease Unacceptable blood pressure control Liver cirrhosis |
Randomized, double-blind, placebo-controlled Phase III Ongoing |
Change in proteinuria in 9 months eGFR in 2 years |
2 years |
| PL-56 in IgAN (NCT00767221) | Budesonide 8 mg once daily for 6 months | Corticosteroid | Albuminuria > 500 mg/day Serum creatinine < 200 μmol/L |
Use of investigational drug within 30 days Using cytochrome P450 enzyme inhibitors |
Open-label Phase II Completed |
Albuminuria at 3 months (No publication posted) |
9 months |
| Complement pathway inhibitors | |||||||
| CCX168 in IgAN (NCT02384317) | Avacopan twice daily for 48 days | C5a receptor inhibitor | Proteinuria > 1 g/g Stabilized on RAAS-i eGFR > 60 mL/min/1.73 m2 |
Use of immunosuppressants within 24 weeks Henoch–Schönlein purpura with systemic manifestations within 2 years Proteinuria > 8 g/g |
Open-label Phase II Completed |
Incidence of adverse events at 169 days (No publication posted) |
169 days |
| LNP023 in kidney disease caused by inflammation (NCT03373461) | Iptacopan twice daily (part 1: 10 mg, 50 mg, 200 mg; part 2: 10 mg, 50 mg, 100 mg, and 200 mg) vs. matching placebo | A factor B inhibitor of the alternative complement pathway | Proteinuria ≥ 1 gm/day at screening and ≥ 0.75 gm/day after the run-in period Stabilized on RAAS-i for at least 90 days eGFR ≥ 30 mL/min/1.73 m2 |
Use of immunosuppressants within 90 days or other investigational drugs within 30 days Plasma donation within 30 days History of porphyria metabolic disorder History of alcohol or drug abuse within 12 months |
Randomized, double-blind, placebo-controlled Phase II Completed |
Reduction of proteinuria at 90 days (No publication posted) |
180 days |
| Narsoplimab in IgAN (NCT02682407) | Narsoplimab vs. matching placebo | Human monoclonal antibody against mannan-associated lectin-binding serine protease-2 (MASP-2) | Proteinuria > 1 gm/day Stabilized on RAAS-i for 6 months |
Use of investigational drugs within 6 months | Open-label Phase II Ongoing |
Treatment-related adverse events Change from baseline in urine and serum complement components |
104 weeks |
| ALXN2050 in LN & IgAN (NCT05097989) | Vemircopan 120 mg vs. Vemircopan 180 mg vs. placebo in IgAN cohort | Factor D inhibitor | Proteinuria ≥ 1 gm/day Presence of hematuria Stabilized on RAAS-i for ≥ 3 months |
Use of glucocorticoid within 6 months Blood pressure > 140/90 mmHg Rapidly progressive glomerulonephritis diagnosis within 3 months |
Randomized, multi-center, double-blind, placebo-controlled Phase II Ongoing |
Change of proteinuria at week 26 | 50 weeks |
| SANCTUARY in LN & IgAN (NCT04564339) | Ravulizumab based on body weight | Terminal complement pathway inhibitor | Proteinuria ≥ 1 gm/day Stabilized n RAAS-i for 3 months |
Use of glucocorticoid within 6 months Previous use of complement inhibitor |
Randomized, double-blind, placebo-controlled Phase II Ongoing |
Change of proteinuria at 26 weeks | 50 weeks |
| B-cell inhibitors | |||||||
| BRIGHT-SC (NCT02062684) | Subcutaneous blisibimod 100 mg three times weekly for 8 weeks then 200 mg weekly for 16 weeks vs. matching placebo | A selective peptibody antagonist of B-cell activating factor | Proteinuria ≥ 1 gm/day but ≤ 6 gm/day at two consecutive time points Stabilized on RAAS-i for 8 weeks |
Use of glucocorticoid within 3 months or immunosuppressants within 6 months Neutropenia |
Randomized, double-blind, placebo-controlled Phase II/III Completed |
Reduction in proteinuria at 42 weeks (No publication posted) |
104 weeks |
| RC18 in IgAN (NCT04291781) | Subcutaneous telitacicept 160 mg once weekly for 24 doses vs. 240 mg once weekly for 24 doses vs. matching placebo | A fusion protein that neutralizes the B lymphocyte stimulator and a proliferation-inducting ligand | Proteinuria ≥ 1 gm/day Stabilized on RAAS-i for 4 weeks eGFR > 45 mL/min/1.73 m2 |
Use of glucocorticoid within 6 months or investigational drug within 4 weeks Cytopenia A cardiovascular event within 12 weeks |
Randomized, double-blind, placebo-controlled Phase II Completed |
Reduction of proteinuria at week 24 (No publication posted) |
24 weeks |
| ORIGIN (NCT04716231) | Atacicept weekly subcutaneous injections vs. matching placebo | Recombinant fusion protein that inhibits B lymphocytes stimulators and a proliferation-inducing ligand | Proteinuria > 0.75 gm/day Stabilized on RAAS-i for 12 weeks |
Rapidly progressive glomerulonephritis Nephrotic syndrome |
Randomized, double-blind, placebo-controlled Phase IIb Ongoing |
Reduction of proteinuria at 24 weeks | 2 years |
| Telitacicept in IgAN (NCT05596708) | Telitacicept 240 mg weekly subcutaneous injection for 104 weeks vs. matching placebo | Recombinant fusion protein that inhibits B lymphocytes stimulators and a proliferation-inducing ligand | Proteinuria ≥ 0.75 gm/day Stabilized on RAAS-i for 12 weeks |
Use of immunosuppressants within 3 months | Randomized, double-blind, placebo-controlled Phase III Ongoing |
Complete clinical response The absolute value of eGFR Reduction of proteinuria |
3 years |
| VISIONARY (NCT05248646) | Sibeprenlimab 400 mg subcutaneous every 4 weeks vs. matching placebo | Humanized monoclonal IgG2 antibody that inhibits a proliferation-inducing ligand | Proteinuria ≥ 1 gm/day Stabilized on RAAS-i for 3 months |
Use of immunosuppressants within 16 weeks Nephrotic syndrome |
Randomized, multi-center, double-blind, placebo-controlled Phase III Ongoing |
Reduction of proteinuria at 9 months | 24 months |
| BION-1301 in IgAN (NCT03945318) | BION-1301 vs. placebo, 2 parts | Humanized monoclonal antibody against a proliferation-inducing ligand | Proteinuria ≥ 0.5 gm/day Stabilized on RAAS-i for 3 months |
Use of glucocorticoid within 3 months | Randomized, multi-center, double-blind, placebo- controlled Phase I/II Ongoing |
Incidence of treatment-emergent adverse events and their severity | 76 weeks |
| IGANZ (NCT05065970) | Felzartamab vs. matching placebo | Anti-CD38+ monoclonal antibody | Proteinuria ≥ 1 gm/day Stabilized on RAAS-i for ≥ 3 months |
Diabetes mellitus type 1 Deranged liver enzymes Cytopenia |
Randomized, multi-center, double-blind, placebo-controlled Phase IIa Ongoing |
Change of proteinuria at 9 months | 2 years |
| AT-1501 in IgAN (NCT05125068) | Tegoprubart 10 mg/kg vs. 5 mg/kg both every 3 weeks for 93 weeks, a total of 32 infusions | Anti-CD40L monoclonal antibody | Proteinuria ≥ 0.75 gm/day Stabilized on RAAS-i for at least 90 days |
Diabetes mellitus Blood pressure > 140/90 mmHg |
Non-randomized, multi-center, open-label Phase IIa Ongoing |
Change of proteinuria at 24 weeks Safety |
100 weeks |
| Rituximab in IgAN (NCT00498368) | Intravenous rituximab 1 g on days 1 and 15, and the course repeated after 6 months vs. matching placebo | A chimeric monoclonal antibody directed against the CD20 antigen of B cells | Proteinuria ≥ 1 gm/day while on stable RAAS-i for 2 months eGFR 30–90 mL/min/1.73 m2 |
Use of glucocorticoid for > 6 months or previous treatment with rituximab or natalizumab History of Crohn’s disease or celiac sprue |
Randomized, multi-center, open-label Phase IV Completed |
Reduction of proteinuria at 12 months [Results showed that rituximab did not significantly improve renal function or proteinuria assessed over a year (48),] |
12 months |
| RITA in IgAN (NCT04525729) | Rituximab (1 g on day 1, day 31, and at 6 months) and RAAS-i vs RAAS-i | A chimeric monoclonal antibody directed against CD20 antigen of B cells | Stabilized on RAAS-i for 3 months | Use of glucocorticoid within 12 months or other immunosuppressants within 6 months | Randomized, multi-center, controlled | Change of proteinuria at 1 year | 1 year |
| Protein degradation inhibitors | |||||||
| Velcade in IgAN (NCT01103778) | Intravenous bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11. A second cycle is to be given for non-responders 1 month later | A proteasome inhibitor | Proteinuria > 1 gm/day Stabilized on RAAS-i for at least 4 weeks |
Use of investigational drug within 14 days Low platelet and neutrophil count Peripheral neuropathy |
Open-label Phase IV Completed |
Reduction of proteinuria at 12 months [Results showed that 38% had achieved the primary end point at 1-year follow-up (49)] |
12 months |
| SIGN (NCT02112838) | Fostamatinib 150 mg twice daily vs. fostamatinib 100 mg twice daily vs. matching placebo | A relatively selective small molecule spleen tyrosine kinase inhibitor | Proteinuria > 1 gm/day at diagnosis of IgAN Stabilized on RAAS-i for at least 90 days eGFR > 30 mL/min/1.73 m2 |
Recent use of immunosuppressants or > 15 mg/day of prednisone | Randomized, multi-center, double-blind, placebo-controlled Phase II Completed |
Reduction of proteinuria at week 24 (No publication posted) |
24 weeks |
| ANG-3070 in chronic kidney disease (NCT04939116) | ANG-3070 200 mg once daily vs. 400 mg once daily vs. 300 mg twice daily vs. placebo for 12 weeks | Oral tyrosine kinase inhibitor | Proteinuria ≥ 1 gm/day Stabilized on RAAS-i eGFR ≥ 40 mL/min/1.73 m2 |
Deranged liver enzymes Type 1 diabetes Positive hepatitis B or C or HIV viral screening |
Randomized, multi-center, double-blind, placebo-controlled Phase II Ongoing |
Change of proteinuria at 12 weeks | 12 weeks |
| Endothelin receptor antagonists | |||||||
| PROTECT (NCT03762850) | Sparsentan 400 mg total vs. irbesartan 300 mg total for 110 weeks | Dual endothelin angiotensin receptors antagonist | Proteinuria ≥ 1 gm/day Stabilized on RAAS-i for 12 weeks Blood pressure ≤ 150/100 mmHg |
Use of glucocorticoid within 3 months History of heart failure |
Randomized, multi-center, double-blind, active-control Phase III Ongoing |
Change of proteinuria at week 36 | 2 years |
| ALIGN (NCT04573478) | Atrasentan 0.75 mg orally daily for 132 weeks vs. matching placebo | Endothelin A antagonist | Proteinuria ≥ 1 gm/day Stabilized on RAAS-i for at least 12 weeks |
Use of immunosuppressants for more than 2 weeks within 3 months | Randomized, multi-center, placebo-controlled Phase III Ongoing |
Change in proteinuria at week 24 | 2.6 years |