The goal of this clinical trial is to learn if a new drug that might help protect and preserve kidney function in antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV). AAV is a type of autoimmune disease where the body's own immune system attacks itself, and in the case of AAV the body attacks its own small blood vessels. There are many small blood vessels in the kidneys meaning the kidneys are commonly affected in AAV. The main questions it aims to answer are: * Is the new drug well tolerated and safe? * Can the new drug protect and preserve kidney functions when is added to standard therapy? Researchers will compare the following groups to see how the new drug is tolerated and what effect to preserve kidney tissue has: * Group A: Standard treatment + ALE.F02 low dose infusions * Group B: Standard treatment + ALE.F02 high dose infusions * Group C: Standard treatment + ALE.F02 maximum dose infusions * Group D: Standard treatment + placebo infusions (inactive substance) The Treatment period will consist of 24 weeks beginning on Day 1, during which time participants will receive 13 infusions of the study medicine, along with standard therapy for kidney inflammation due to AAV. During the treatment period, participants will have the following assessments: * A brief physical examination focusing on their skin any pre-existing medical conditions that you have. * Collection of blood and urine samples for routine safety tests and to assess renal function. * Collection of blood samples: * To measure the amount of study medicine in their blood. This is called pharmacokinetics (PK) and it is tested to see how study medicine enters, moves through, and exits the body. * To test for antidrug antibodies (ADA). To check if their body create antibodies against the study medicine, as this could reduce its effect. * To measure biomarkers. Biomarkers are specific compounds in the body (can be protein, hormones, or genetic molecules) that indicate normal or abnormal processes taking place in your body and may be a sign of an underlying condition or disease (for example glucose levels are used as biomarker in managing diabetes). They are used to see how well the body responds to a treatment for a disease or condition. * Collection of urine to measure urine markers of vasculitis/inflammation called biomarkers. * Urine pregnancy test. A urine pregnancy test is a quick medical test that can tell if a woman is pregnant or not by checking for a hormone which is produced during pregnancy, usually in the urine. * Chest High Resolution Computed Tomography (HRCT) scan to check whether they have vasculitis affecting their lungs. A CT scan uses special x-ray equipment to take detailed pictures of body tissues and organs to diagnose and monitor conditions in various parts of the body. For the CT scan, they will need to lie still on a table. At Week 24 a second lung CT scan will be performed for participants whose initial scan showed lung vasculitis to see whether your lung vasculitis is getting better or ongoing/worse.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
80
ALE.F02 is an anti-Claudin-1 (CLDN1) monoclonal antibody (mAb) to selectively target the non-tight junctions (TJ), exposed form of CLDN1. CLDN1 is an integral component of the TJs between cells.
Rituximab is a monoclonal antibody that targets cluster of differentiation antigen 20 (CD20), an antigen expressed on the surface of pre-B and mature B-lymphocytes
Glucocorticoids are a class of corticosteroids, which are a class of steroid hormones that bind to the glucocorticoid receptor. Glucocorticoid effects may be broadly classified into two major categories: immunological and metabolic.
Cyclophosphamid is a medication used as chemotherapy and to suppress the immune system
Drug product that will contain no active ingredient
Immunosuppressants are drugs that prevent your immune system from attacking healthy cells and tissues by mistake.
Vseobecna fakultni nemocnice v Praze
Prague, Czechia
RECRUITINGInstitut klinicke a experimentalni mediciny
Prague, Czechia
RECRUITINGAalborg University Hospital
Aalborg, Denmark
RECRUITINGAarhus University Hospital
Aarhus, Denmark
The primary endpoint for this study is the safety and tolerability of ALE.F02 when administered as a continuous IV infusion in patients with rapidly progressive glomerulonephritis (RPGN) attributed to AAV.
Safety endpoints are the following: * All adverse events (AEs); * All serious adverse events (SAEs); * Hematology and clinical chemistry analyte assessments; * Serum lipids; * Antidrug antibodies (ADAs); and * ECGs
Time frame: through study completion, an average of 1 year
The key secondary endpoint for this study is the change in mean estimated glomerular filtration rate (eGFR) from baseline to Week 24/End of Treatment (EOT) for recipients of ALE.F02 compared to placebo.
Time frame: from baseline to Week 24/EOT
Change in mean urine protein to creatinine ratio (UPCR) area under the concentration time curve (AUC) from baseline to Week 24/EOT for recipients of ALE.F02 compared to placebo;
Time frame: from baseline to Week 24/EOT
Change in mean urine protein to creatinine ratio (UPCR) area under the concentration time curve (AUC) from baseline to Week 52/End of Study (EOS) for recipients of ALE.F02 compared to placebo;
Time frame: from baseline to Week 52/EOS
Time to stable proteinuria (≤0.5 g/day for ≥14 days) during the Treatment Period for recipients of ALE.F02 compared to placebo;
Time frame: up to 24 weeks
Time to stable hematuria (≤5 RBCs/high-power field for ≥14 days) during the Treatment Period for recipients of ALE.F02 compared to placebo;
Time frame: up to 24 weeks
Incidence of renal replacement therapy (RRT) at any time during the study for recipients of ALE.F02 compared to placebo; and
Time frame: through study completion, an average of 1 year
Total glucocorticoid and immunosuppressive exposure at Week 24/EOT and Week 52/EOS for recipients of ALE.F02 compared to placebo.
Time frame: at Week 24/EOT and Week 52/EOS
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Rigshospitalet
Copenhagen, Denmark
RECRUITINGOdense University Hospital
Odense, Denmark
RECRUITINGCentre Hospitalier Boulogne sur Mer
Boulogne-sur-Mer, Cedex, France
RECRUITINGCHU Bordeaux - Hopital Pellegrin
Bordeaux, France
RECRUITINGCHRU de Brest - Hopital de la Cavale Blanche
Brest, France
RECRUITINGCHU Grenoble-Alpes - Hopital Michallon
La Tronche, France
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