Avacopan in Crescentic Immunoglobulin A Nephropathy (IgAN)

NCT06676579 | Recruiting Phase 2 FDA Drug

• 1 other identifier: 24-005668
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

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)

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Change in proteinuria >50%

  12 months

• Change in eGFR (using 2021 CKD-EPI Formula)

  6 months, 12 months

• Change in hematuria from Baseline to 12 month visit.

  12 months

Study Arms (2)

Avacopan and Low Doses Glucocorticoid

ACTIVE COMPARATOR

* 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; Drug: Methylprednisolone (drug); Drug: Prednisolone

High Doses Glucocorticoid

ACTIVE COMPARATOR

* 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: Prednisone; Drug: Methylprednisolone (drug)

Interventions

Avacopan DRUG

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

Also known as: Tavneos

Avacopan and Low Doses Glucocorticoid

Prednisone DRUG

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

High Doses Glucocorticoid

Methylprednisolone (drug) DRUG

Methylprednisolone 1g intravenous on day +1

Avacopan and Low Doses Glucocorticoid; High Doses Glucocorticoid

Prednisolone DRUG

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 and Low Doses Glucocorticoid

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (2)

Mayo Clinic in Florida

Jacksonville, Florida, 32224, United States

RECRUITING

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

MeSH Terms

Conditions

Glomerulonephritis, IGA

Interventions

avacopan; Prednisone; Methylprednisolone; Pharmaceutical Preparations; Prednisolone

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienetriols

Study Officials

• Fernando Fervenza, MD

  Mayo Clinic, Rochester, MN

  PRINCIPAL INVESTIGATOR

• Nabeel Aslam, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Corbyn Bendtsen

CONTACT

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

Zach Monson

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 29, 2024
• First Posted: November 6, 2024
• Study Start: June 9, 2025
• Primary Completion (Estimated): March 2, 2028
• Study Completion (Estimated): March 2, 2029
• Last Updated: October 3, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)