Recruiting
Phase 2

Avacopan with Glucocorticoid

Sponsor:

Mayo Clinic

Code:

NCT06676579

Conditions

IgA Nephropathy (IgAN)

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Avacopan

Prednisone

Methylprednisolone (drug)

Prednisolone

Study Details

Brief summary:

The purpose of this study is to evaluate the efficacy and safety of Avacopan together with low-dose glucocorticoid in the treatment of patients with crescentic Imunoglobulin A Nephropathy (IgAN) and high risk of progression.

Conditions

IgA Nephropathy (IgAN)

Study ID

NCT06676579

Start date

Jun 9, 2025

Status verified date

Oct, 2025

Completion date

Mar 2, 2029

Anticipated

Primary completion date

Mar 2, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

16 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: Avacopan and Low Doses Glucocorticoid

  • Methylprednisolone 1g intravenous on day +1
  • Prednisone 0.2 mg/kg per day (maximum, 16 mg/day) for 2 months followed by dose tapering by 2 mg per day each month (total duration 6-9 months)
  • Avacopan 30 mg oral twice a day (1-0-1) for 12 months

active comparator: High Doses Glucocorticoid

  • Methylprednisolone 1g intravenous on day +1
  • Prednisone 0.4 mg/kg per day (maximum, 32 mg/day) for 2 months followed by dose tapering by 4 mg per day each month (total duration 6-9 months)

Interventions

Avacopan

Avacopan is a complement 5a receptor (C5aR) antagonist, orally active.

Prednisone

0.4 mg/kg per day (maximum, 32 mg/day) for 2 months followed by dose tapering by 4 mg per day each month (total duration 6-9 months

Methylprednisolone (drug)

Methylprednisolone 1g intravenous on day +1

Prednisolone

Prednisone 0.2 mg/kg per day (maximum, 16 mg/day) for 2 months followed by dose tapering by 2 mg per day each month (total duration 6-9 months)

Primary outcome measure

  • Change in proteinuria measured by results of protein total, 24-hour urine collection at baseline compared to collection at 12 months. [ Time Frame: 12 months ]

Central Contacts and Locations

Central contacts

Corbyn Bendtsen

507-284-0366bendtsen.corbyn@mayo.edu

Zach Monson

507-255-0387monson.zachari@mayo.edu

Locations

Mayo Clinic in Florida

Recruiting

Jacksonville, Florida, United States, 32224

Principal Investigator:

Nabeel Aslam

Mayo Clinic in Rochester

Recruiting

Rochester, Minnesota, United States, 55905

Principal Investigator:

Fernando Custodio Fervenza

More Information

Sponsor

Mayo Clinic

Last update posted

Oct 3, 2025

Last verified

Oct, 2025

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-25. This information was provided to ClinicalTrials.gov by Mayo Clinic on 2025-10-03. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.