Avacopan added to standard-of-care therapy in ANCA-associated vasculitis with severe kidney involvement

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Toulouse

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

1 Jun 2026 → ongoing

Decision date (initial)

2025-11-27

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To demonstrate an improvement in the kidney function at week 52 (eGFR > or =30 mL/min/1.73m2; i.e. CKD stage 1-3) in patients with severe forms of AAV-associated RPGN (eGFR 0-29 mL/min/1.73m2 at inclusion) when avacopan is added to GCs-based SOC.

Secondary objectives 9

1. To assess survival in both groups up to week 64
2. To assess in both groups the vasculitis activity: Birmingham Vasculitis Activity Score (BVAS) and Vasculitis Damage Index (VDI) at weeks 20, 52 and 64
3. To assess in both groups the occurrence of treatment-related adverse events
4. To assess in both groups the kidney function (eGFR and proteinuria) at weeks 20, 52 and 64
5. To assess in both groups the proportion of end-stage kidney disease (chronic dialysis) at weeks 20 52 and 64
6. To assess in both groups the intensity of kidney inflammation (urinary levels of soluble CD163 and MCP1; urinary and serum levels of C3a, C5a and factor Bb) at inclusion and at weeks 4, 12, 20 and 52)
7. To assess in both groups changes in quality of life from baseline to week 64
8. To assess the ability of kidney biopsy to predict the renal response to avacopan, in those receiving avacopan (per-protocol analysis)
9. Conservation of blood and urines samples for future biological analyses

Conditions and MedDRA coding

ANCA-associated vasculitis

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Are male or female, 18 to 85 years of age
2. Kidney biopsy before inclusion available (up to 6 weeks before inclusion) or patients agreeing to have a renal biopsy procedure performed no later than prior the visit at week 4
3. Have been newly diagnosed or relapsing active AAV-related RPGN at the time of inclusion (either granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA), according to the American College of Rheumatology/European League Against Rheumatism 2022 (ACR/EULAR 2022) classification criteria, with or without positive ANCA testing)
4. Have an active disease (BVAS ≥ 3, with at least one of the 2 renal items of proteinuria (urinary proteinuria/creatininuria > 300 mg/g) and haematuria (>10 RBC/hpf) within the BVAS), and eGFR 0-29 mL/min/1.7 m2 at inclusion
5. Be planned to receive a SOC induction regimen by rituximab or cyclophosphamide plus glucocorticoids (+ or - plasma exchanges) for the current AAV flare (rituximab or cyclophosphamide may have been started before the inclusion in the study, maximum 2 weeks before the inclusion)
6. Affiliated person or beneficiary of a social security scheme.
7. Free, informed and written consent signed by the participant and the investigator (at the latest on the day of inclusion and before any examination required by the research).
8. For women able to procreate, ongoing effective contraception

Exclusion criteria 22

1. Irreversible medical conditions likely to affect short-term survival or ability to participate in the study protocol
2. Human immunodeficiency virus (HIV) positivity.
3. Acute or chronic infection with hepatitis B (HBV) or hepatitis C (HCV
4. Positive serology for hepatitis B core antibody (HBcAb) or hepatitis B surface antigen (HBsAg) excludes the participant regardless of detection of hepatitis B surface antibodies (HBsAb) or HBV-DNA
5. Participants with a positive HCV antibody test should have HCV ribonucleic acid (RNA) levels measured. Participants with positive (detectable) HCV RNA must be excluded. Chronic hepatitis C participants, who have completed anti- HCV treatment for at least 12 weeks must have a negative HCV RNA result before randomization. Cases of spontaneous HCV clearance should be discussed with sponsor before enrolment.
6. Active viral, bacterial or other infections requiring systemic treatment, or history of recurrent clinically significant infection which in the opinion of the investigator will place the participant at risk for participation.
7. Uncontrolled diabetes mellitus, lung diseases or any other illnesses not related to GPA/ MPA that in the opinion of the Investigator would jeopardize the ability of the patient to tolerate glucocorticoids
8. History of lymphoproliferative disease or any known malignancy or history of malignancy of any organ system within the past 3 years (except for basal cell carcinoma or actinic keratosis that have been treated with no evidence of recurrence in the past 3 months, carcinoma in situ of the cervix or non-invasive malignant colon polyps that have been removed).
9. Severe heart failure history (i.e., LVEF < 30%)
10. Solid organ transplantation
11. Use of other investigational drugs at the time of enrollment, or within 5 half-lives of enrollment, or within 30 days, whichever is longer; or longer if required by local regulations.
12. Treatment by >3000 mg methylprednisolone or equivalent within the 3 weeks preceding the screening visit
13. Pregnancy or breastfeeding
14. Patient under legal protection.
15. Known eGFR before the AAV flare already <35 mL/min/1.73m2
16. Glomerulosclerosis >60% or kidney interstitial fibrosis >60%, if results of a kidney biopsy are available. If kidney biopsy is performed after inclusion in the study, the patients will continue the study according to the protocol whatever the extent of glomerulosclerosis or interstitial fibrosis.
17. • Pregnant or breast-feeding women, or desire to become pregnant within 24 months. All women of childbearing potential (WOCBP) are required to have a negative pregnancy test before treatment and must agree to maintain highly effective contraception by practicing abstinence or by using an effective method of birth control from the date of consent through the end of the study and another 12 months after (or 12 months after the last rituximab infusion in case of premature termination)
18. Hepatic dysfunction defined as: ALT, AST or alkaline phosphatase > 3 ×ULN Total Bilirubin >2 × ULN, with the exception of participants with Gilbert syndrome who may be included if their total bilirubin is ≤ 3.0 × ULN and direct bilirubin ≤ 1.5 × ULN International normalized ratio (INR) >1.7 (excepted if patient receive vitamin K antagonists)
19. Co-administration of strong CYP3A4 enzyme inducers
20. Known allergy to avacopan
21. Other clinically active systemic autoimmune disease requiring therapy, including but not limited to: eosinophilic granulomatosis with polyangiitis (EGPA), moderate to severe systemic lupus erythematosus, IgA vasculitis (Henoch-Schönlein), rheumatoid vasculitis, Sjögren's syndrome, cryoglobulinemic vasculitis, autoimmune hemolytic anemia, autoimmune lymphoproliferative syndrome or mixed connective tissue disease.
22. • Patients with leukocytes below 2000/mm3 or neutrophils below 1000/mm3 will be excluded. However, since patients may have received rituximab or cyclophosphamide before inclusion as a part of induction regimen of the AAV (see inclusion criteria), and both are considered as lymphodepleting agent, mild to moderate lymphopenia (400 – 1500/mm3) at randomization will be allowed

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of patients reaching an estimated glomerular filtration rate > or =30 mL/min/1.7m² (CKD-EPI formula applied to the measure of standardized serum creatinine) at week 52 without requiring treatment study discontinuation for serious adverse event or treatment modification or intensification for refractory vasculitis or relapse

Secondary endpoints 11

1. Survival (at week 52 and 64; % and survival curves)
2. Birmingham Vasculitis Activity Score (BVAS; evaluation at weeks 0, 20, 52, 64) and Vasculitis Damage Index (change between baseline (week 0) and weeks 20, 52 and 64, respectively)
3. Proportion of patients achieving disease remission (defined as BVAS score = 0) at weeks 20, 52 and 64
4. Changes in eGFR from baseline (in mL/min/1.7m2; CKD-EPI formula derived from the serum creatinine) and weeks 20, 52 and 64, respectively
5. Urinary protein/creatinine ratio (mg/mmol) and urinary albumin/creatinine ratio (mg/mmol) at week 20, 52 and 64
6. Number and percentage of patients requiring chronic dialysis at weeks 20, 52 and 64
7. Urinary levels of MCP-1 and soluble CD163
8. Urinary and serum levels of C3a, C5a and factor Bb (evaluation at inclusion and at weeks 4, 12, 20, and 52)
9. Short Form-36 v.2 component and domain scores and the EuroQOL-5D-5L visual analogue scale (in mm) and index: change between baseline and week 64
10. Brix / Berden scores, C3 deposits in glomeruli, interstitial fibrosis, glomerulosclerosis, percentage of extra-capillary crescents measured at baseline
11. Occurrence of infections, diabetes mellitus, hepatitis and other adverse events (inclusion to week 64)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Toulouse

Sponsor organisation

Centre Hospitalier Universitaire De Toulouse

Address

2 Rue Viguerie

City

Toulouse

Postcode

31300

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Toulouse

Contact name

principal investigator

Public contact point

Organisation

Centre Hospitalier Universitaire De Toulouse

Contact name

clinical research project manager

Locations

1 EU/EEA country · 30 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications