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Avacopan added to standard-of-care therapy in ANCA-associated vasculitis with severe kidney involvement
EU CTIS ID: 2024-519620-24-01
What this study is testing
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.
- Therapeutic confirmatory (Phase III)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Are male or female, 18 to 85 years of age
- 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
- 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)
- 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
- Be planned to receive a SOC induction regimen by rituximab/obinutuzumab (pour les patients allergiques ou intolérant au rituximab) or cyclophosphamide plus glucocorticoids (+ or - plasma exchanges) for the current AAV flare (rituximab/obinutuzumab or cyclophosphamide may have been started before the inclusion in the study, maximum 2 weeks before the inclusion)
- Affiliated person or beneficiary of a social security scheme.
You likely can't join if
- Irreversible medical conditions likely to affect short-term survival or ability to participate in the study protocol
- 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)
- Co-administration of strong CYP3A4 enzyme inducers
- Human immunodeficiency virus (HIV) positivity.
- Known allergy to avacopan
- 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.
See the full eligibility criteria
Who can join
- Are male or female, 18 to 85 years of age
- 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
- 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)
- 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
- Be planned to receive a SOC induction regimen by rituximab/obinutuzumab (pour les patients allergiques ou intolérant au rituximab) or cyclophosphamide plus glucocorticoids (+ or - plasma exchanges) for the current AAV flare (rituximab/obinutuzumab or cyclophosphamide may have been started before the inclusion in the study, maximum 2 weeks before the inclusion)
- Affiliated person or beneficiary of a social security scheme.
- 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).
- For women able to procreate, ongoing effective contraception
What rules you out
- Irreversible medical conditions likely to affect short-term survival or ability to participate in the study protocol
- 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)
- Co-administration of strong CYP3A4 enzyme inducers
- Human immunodeficiency virus (HIV) positivity.
- Known allergy to avacopan
- 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.
- • 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
- Acute or chronic infection with hepatitis B (HBV) or hepatitis C (HCV
- 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
- 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.
- 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.
- Solid organ transplantation
- 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
- 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).
- Severe heart failure history (i.e., LVEF < 30%)
- Positive anti-glomerular basement membrane (GBM) antibodies (ELISA threshold 0.9 AI) or linear IgG deposits along the GBM on kidney biopsy
- 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.
- Treatment by >3000 mg methylprednisolone or equivalent within the 3 weeks preceding the screening visit
- Pregnancy or breastfeeding
- Patient under legal protection.
- Known eGFR before the AAV flare already <35 mL/min/1.73m2
- 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.
- • 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)
The study team makes the final eligibility decision.
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18-64 years, 65+ years. The study team makes the final eligibility decision.
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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.