Avacopan in Crescentic Immunoglobulin A Nephropathy (IgAN)

A Multi-Center, Phase II, Open Label, Randomized Trial Evaluating the Efficacy and Safety of Complement 5a Receptor Antagonist Avacopan in Crescentic IgA Nephropathy

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.

Study Overview

• Status: Recruiting
• Conditions: IgA Nephropathy (IgAN)
• Intervention / Treatment: Drug: Avacopan; Drug: Methylprednisolone (drug); Drug: Prednisolone; Drug: Prednisone

• Study Type: Interventional
• Enrollment (Estimated): 16
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Corbyn Bendtsen; Phone Number: 507-284-0366; Email: bendtsen.corbyn@mayo.edu
• Study Contact Backup: Name: Zach Monson; Phone Number: 507-255-0387; Email: monson.zachari@mayo.edu

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Recruiting
      • Mayo Clinic in Florida
      • Principal Investigator: Nabeel Aslam
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic in Rochester
      • Principal Investigator: Fernando Custodio Fervenza

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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	Drug: Avacopan; Avacopan is a complement 5a receptor (C5aR) antagonist, orally active.; Other Names: Tavneos; Drug: Methylprednisolone (drug); Methylprednisolone 1g intravenous on day +1; Drug: 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)
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)	Drug: Methylprednisolone (drug); Methylprednisolone 1g intravenous on day +1; Drug: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in proteinuria measured by results of protein total, 24-hour urine collection at baseline compared to collection at 12 months.	A response is based on the average of proteinuria quantified twice over a 2-weeks period at 12 months.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in proteinuria >50%	This is based on the average of proteinuria quantified twice over a 2-weeks period at 12 months.	12 months
Change in eGFR (using 2021 CKD-EPI Formula)	• Change in eGFR (using 2021 CKD-EPI Formula) at 6 and 12 months compared to baseline	6 months, 12 months
Change in hematuria from Baseline to 12 month visit.	Hematuria is measured in the urinalysis done at baseline and 12-month visit.	12 months

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Fernando Fervenza, MD, Mayo Clinic, Rochester, MN; Principal Investigator: Nabeel Aslam, MD, Mayo Clinic

Study record dates

Study Major Dates

• Study Start (Actual): June 9, 2025
• Primary Completion (Estimated): March 2, 2028
• Study Completion (Estimated): March 2, 2029

Study Registration Dates

• First Submitted: October 29, 2024
• First Submitted That Met QC Criteria: November 4, 2024
• First Posted (Actual): November 6, 2024

Study Record Updates

• Last Update Posted (Estimated): October 3, 2025
• Last Update Submitted That Met QC Criteria: October 1, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Autoimmune Diseases; Immune System Diseases; Glomerulonephritis; Nephritis; Glomerulonephritis, IGA; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Pregnadienetriols; Pregnadienediols; Prednisone; Prednisolone; Methylprednisolone; avacopan; Pharmaceutical Preparations
• Other Study ID Numbers: 24-005668

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No