Avacopan in Crescentic Immunoglobulin A Nephropathy (IgAN)

Launched by MAYO CLINIC · Nov 4, 2024

Keywords

ClinConnect Summary

This clinical trial is looking at a new treatment called Avacopan for patients with a kidney condition known as crescentic IgA Nephropathy (IgAN). The goal is to see if Avacopan, used alongside a low dose of a common steroid medication (glucocorticoid), can help improve kidney health for people who are at high risk of their condition getting worse. The trial is not yet open for enrollment, but once it begins, it will include adults over 18 who have had a kidney biopsy showing this specific type of IgAN, and who have certain levels of kidney function and protein in their urine.

If eligible and chosen to participate, patients can expect to receive dietary and lifestyle advice before starting the treatment. They will need to follow a low-protein and low-sodium diet, and control their blood pressure. Participants will be monitored closely throughout the study to ensure their safety. It’s important to note that individuals with certain health issues, such as severe liver problems or recent serious infections, will not be able to join the trial. Overall, this study aims to find out if Avacopan can be an effective and safe option for treating this challenging kidney disease.

Gender

ALL

Eligibility 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.