Nephrology · Clinical trials
IgA Nephropathy Clinical Trials
Approved therapies, the pivotal-trial endpoints they were judged on, the magnitude of benefit — and the drugs that failed their endpoints, and why.
Indication overview
About iga nephropathy — and why its trials are hard
IgA nephropathy (IgAN, Berger disease) is the most common primary glomerulonephritis worldwide and a leading cause of kidney failure in young adults. Galactose-deficient IgA1 triggers immune-complex deposition in the glomerular mesangium, driving inflammation, proteinuria and progressive loss of kidney function; a substantial fraction of patients reach kidney failure within two decades. For years management was limited to optimized renin-angiotensin system blockade, blood-pressure control and supportive care, with systemic corticosteroids used cautiously given toxicity. The landscape shifted dramatically after 2021 as disease-modifying agents reached the market: targeted-release budesonide acting on gut-associated lymphoid tissue, the dual endothelin/angiotensin receptor antagonist sparsentan, the endothelin antagonist atrasentan, and complement pathway inhibitors such as iptacopan. SGLT2 inhibitors add further nephroprotection. Regulatory approvals initially relied on proteinuria surrogate endpoints under accelerated pathways, later confirmed by eGFR slope data. Proteinuria reduction and slowing eGFR decline are now the central efficacy measures guiding treatment selection and sequencing in this rapidly evolving field.
Approved therapies & pivotal evidence
What's been approved — and by how much it moved the endpoint
| Drug (brand) | Approved | Setting | Pivotal trial | Primary endpoint | Magnitude of benefit |
|---|---|---|---|---|---|
| sparsentan (Filspari) | 2023 | Adults with primary IgAN at risk of rapid progression (accelerated approval 2023; full approval 2024) | PROTECT (Phase 3) | Change in urine protein-creatinine ratio (UPCR) at 36 weeks; confirmatory eGFR slope | 49.8% reduction in proteinuria from baseline vs 15.1% with irbesartan at week 36; full approval based on significantly slower eGFR decline |
| budesonide (targeted-release) (Tarpeyo (US) / Nefecon (EU)) | 2021 | Adults with primary IgAN at risk of progression (accelerated approval 2021; full approval Dec 2023) | NefIgArd (Phase 3) | UPCR reduction at 9 months; confirmatory 2-year eGFR | ~27% reduction in UPCR vs placebo at 9 months; ~2.5 mL/min/1.73m2 eGFR benefit preserved over 2 years supporting full approval |
| atrasentan (Vanrafia) | 2025 | Adults with primary IgAN at risk of rapid progression (accelerated approval) | ALIGN (Phase 3) | Change in proteinuria (UPCR) at week 36 | ~36% reduction in proteinuria vs placebo at week 36 (unverified exact value) |
Where trials have failed
Drugs that missed their endpoint — and what contributed
The most instructive lessons in iga nephropathy development come from programmes that failed the endpoint that mattered.
| Drug / trial | Endpoint outcome | What contributed |
|---|---|---|
| mycophenolate mofetil (MMF) — Multiple RCTs in Caucasian/Western populations (e.g., Frisch 2005; Hogg 2015) | Did not consistently reduce proteinuria or preserve kidney function in non-Asian IgAN populations | Heterogeneous populations, possible pharmacogenomic and pharmacokinetic differences across ethnic groups, small samples, and background RAS-blockade masking any effect |
| systemic corticosteroids (high-dose oral) — STOP-IgAN; TESTING (early high-dose arm) | STOP-IgAN showed added immunosuppression did not meaningfully improve outcomes over supportive care; TESTING high-dose arm was halted for excess serious adverse events | Serious infections and treatment-related toxicity outweighed benefit, prompting a lower-dose regimen in TESTING |
Choosing the right endpoint
Primary endpoints that matter in iga nephropathy trials
- Proteinuria (UPCR/UACR) — Accepted surrogate for accelerated approvals; reduction correlates with slower progression
- eGFR slope — Rate of kidney function decline; the confirmatory hard endpoint for full approval
- Time to kidney failure/ESKD — Definitive clinical outcome but requires long follow-up
- Galactose-deficient IgA1 / complement biomarkers — Emerging mechanistic biomarkers used exploratorily to gauge target engagement
How iNGENū runs iga nephropathy trials
Physician-led design, built for FDA submission
Endpoint & biomarker strategy
Board-certified specialists design endpoints and patient selection aligned to current FDA guidance for this indication.
FDA-ready data
Built to ICH-GCP and 21 CFR 312.120, with direct FDA submission — data accepted by the FDA, EMA and MHRA.
Faster, lower-cost delivery
~4-week ethics via the TGA CTN scheme, up to 43.5% R&D rebate, and 80–90% below US CRO cost.
Request a fixed-milestone proposal and a tailored endpoint & feasibility summary for this indication.
Frequently asked questions
IgA Nephropathy clinical trials — FAQs
Is there a cure for IgA nephropathy?
Why is proteinuria used to approve IgAN drugs?
Do SGLT2 inhibitors help in IgAN?
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