Avacopan plus low-dose steroid for crescentic IgA nephropathy
Official title: A Multi-Center, Phase II, Open Label, Randomized Trial Evaluating the Efficacy and Safety of Complement 5a Receptor Antagonist Avacopan in Crescentic IgA Nephropathy
Run by Mayo Clinic · NCT06676579 · Data updated 2026-11-12
This trial will test whether adding avacopan to low-dose glucocorticoids helps adults with crescentic IgA nephropathy who are at high risk of kidney progression.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Ages | 18 Years and up |
| Sex | All |
| Enrollment | 16 (estimated) |
| Sponsor | Mayo Clinic Academic / other |
| Drugs / interventions | Rituximab |
| Locations | 2 sites (Jacksonville, Florida and 1 other locations) |
| Status | Recruiting |
| Started | June 9, 2025 |
| Main results expected | March 2028 |
| Study ends | March 2029 |
| Registry record updated | October 9, 2026 |
| Trial ID | NCT06676579 on ClinicalTrials.gov |
Is this trial a fit for you?
✓Likely a good fit
Adults over 18 with a kidney biopsy within six months showing crescentic IgA nephropathy, proteinuria >750 mg/24h despite maximized RAS blockade, and creatinine clearance >20 ml/min/1.73 m2 are the intended participants.
✕Probably not a fit
Patients with advanced kidney failure below the creatinine clearance threshold, without crescentic lesions on biopsy, or who cannot tolerate RAS blockade or glucocorticoids are unlikely to benefit from this protocol.
A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.
What this trial studies
This Phase 2 interventional trial gives adults with biopsy-proven crescentic IgA nephropathy avacopan together with low-dose glucocorticoids on top of standard supportive care to measure safety and effects on kidney outcomes. Eligible participants have recent kidney biopsies showing crescents, significant proteinuria despite maximized RAS blockade, and reasonable kidney function. Patients undergo a run-in period with optimized blood pressure, RAS blockade, dietary counseling, and lifestyle measures before starting the investigational regimen. The study is conducted at Mayo Clinic sites and will monitor kidney function, proteinuria, hematuria, and adverse events to judge whether this approach merits larger trials.
Why it matters
Potential benefit: If successful, this approach could reduce inflammation and slow or prevent rapid kidney decline in patients with crescentic IgA nephropathy while using lower steroid doses.
How similar studies have gone: Avacopan has shown benefit in ANCA-associated vasculitis, but its use specifically for crescentic IgA nephropathy is novel and has limited direct evidence to date.
Who can join: the full rules
Show full inclusion / exclusion criteria
Inclusion Criteria * Age \> 18 years * Kidney biopsy showing crescentic IgA nephropathy within 6 months of enrolment (MEST-C-score =C1/C2). * Quantified creatinine clearance \>20 ml/min/1.73m2 * Quantified Proteinuria \> 750 mg/24h based on a 24h urine collection while on maximum tolerated dose of RAS blockade * Hematuria defined as \>10 RBC/hpf or hemoglobinuria \>1+ * Patients need to be in adequate supportive care (blood pressure \<125/85mmHg, lifestyle advice, and maximum doses tolerable of RAS blockade) at least 4 weeks prior to enrollment * Patients would receive dietary and lifestyle counseling prior enrollment: low protein (0.8-1.0 g/kg/day) diet, low sodium (2 grams/day) intake, indication for smoke cessation, during the 4 weeks run-in period * Has signed an informed consent form prior to any study-related procedures * Patients with documented use of RAS blockade and adequate blood pressure control (\<125/85 mmHg) for ≥4 weeks, can be enrolled in the study and randomized without repeating a 4-week run-in period. Exclusion Criteria * Creatinine clearance \<20 ml/min/1.73 m2 * Liver function tests \> 2x upper limit of normal. (Serious cases of hepatotoxicity have been reported in patients with avacopan during first approval and ADVOCATE study (29) (30) * Severe interstitial fibrosis and tubular atrophy (IFTA \> 70% on renal biopsy) * Active cancer or acute non-controlled infection (including HIV, HBV, HCV) * Women who are pregnant or breastfeeding * Immunosuppression treatment: * Rituximab less than 12 months prior to enrollment * MMF, CYC, or immunomodulatory agents within 3 months prior to enrollment * AZA within 3 months prior to enrollment. * Glucocorticoids \>20 mg/day within 1 month prior to enrollment * Secondary IgA nephropathy (associated with gastrointestinal diseases, infection, autoimmune, malignancy, respiratory tract, or skin) * ANCA-associated vasculitis or other vasculitis diagnostic defined by ACR criteria/Chapel Hill Consensus conference * Contraindication to use any of the protocol treatments (glucocorticoids, avacopan) * Use of a strong/moderate CYP3A4 inducer * Initiation of SGLT2 inhibitors is not allowed once patient has been enrolled in the study. Patients who have been on an SGLT2 inhibitor prior to enrollment on the study may continue on this therapy, at the same dose. No dose increase is allowed. * Active, untreated and/or uncontrolled chronic liver disease (chronic active hepatitis B, untreated hepatitis C, uncontrolled autoimmune hepatitis, cirrhosis * Unable to give written consent form * As a safety measure patients who are pregnant or lactating will not be enrolled in the study.
Where it's running
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Mayo Clinic in Florida
Jacksonville, Florida, United States Recruiting -
Mayo Clinic in Rochester
Rochester, Minnesota, United States Recruiting
Study contacts
- Principal investigator: Fernando Fervenza, MD — Mayo Clinic, Rochester, MN
- Study coordinator: Corbyn Bendtsen
- Email: bendtsen.corbyn@mayo.edu
- Phone: 507-284-0366
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How to take part
- Review the eligibility criteria above with your treating physician.
- Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
- Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.