Imlifidase in ANCA-associated Vasculitis

Prior treatment

• Previous treatment with imlifidase
• Previous or ongoing high dose IVIg treatment (2 g/kg) within 28 days prior to inclusion
• More than two plasma exchanges prior to administration of imlifidase within 28 days prior to inclusion
• Participation in an other interventional clinical trial or intake of other investigational medicinal product within 5 half-lives (or similar) of the product prior to inclusion
• Ongoing bacterial or fungal infection requiring antibiotic /-fungal therapy (or completed within 7 days prior to inclusion). Viral infection with Hepatitis B, C and HIV (up to 14 days old negative test results are accepted); or active tuberculosis as indicated by chest X-ray. Every patient will be screened for SARS-CoV2, positive cases will be excluded.
• Concomitant autoimmunological disease (e.g. Goodpasture, vasculitis other than AAV)
• Concomitant pulmonary disease (e.g. chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD))

Other illness

• Symptomatic congestive heart failure (NYHA class 2-4) requiring prescription medication or clinically evident peripheral edema of cardiac origin or documented evidence/history of NYHA class 2-4 heart failure
• Active malignant disease or a history of malignancy within two years prior to diagnosis/infusion other than non-melanoma resected or cured skin cancer
• Any condition that in the opinion of the investigator could increase the subject's risk by participating in the study other than those specified.
• Present or history of thrombotic thrombocytopenic purpura (TTP), or known familial history of TTP
• Subjects deprived of freedom i.e., detainment or commitment to psychiatric ward, prison or state institution by law court or legal authority
• Known allergy/sensitivity to imlifidase, IVIg and/or the respective excipients

Lab values

• A comorbidity or indication of such based on medical history, physical examination, and clinical laboratory assessments which precludes the use of cyclophosphamide, glucocorticoids, or imlifidase.
• Evidence of moderate or severe hepatic impairment indicated by elevated aminotransferases (ALT or AST) or bilirubin greater than double (2.0 x) the upper limit of normal (ULN)

Age

• Subjects aged < 18 or > 80 years

Other

• Subjects physically or mentally unable to give written informed consent
• Subject who might be dependent on the sponsor, the investigator or the trial site.
• Female subjects: pregnant or breastfeeding or of childbearing potential
• Male subjects: unwilling to use double-barrier contraception for the duration of this study.
• Diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA) consistent with revised Chapel Hill definitions

• New or previous clinical diagnosis of ANCA-associated vasculitis, (granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) consistent with revised Chapel Hill definitions
• ANCA titer >= 50 (AU/ml) (i.e. anti-myeloperoxidase / antiproteinase 3) no more than 14 days prior to inclusion measured by certified clinical laboratory
• Pulmonary hemorrhage due to active vasculitis defined by the following: o A compatible chest x-ray or CT scan (diffuse pulmonary infiltrates) o The absence of an alternative explanation for all pulmonary infiltrates (i.e. volume overload or pulmonary infection) o At least one of the following: § Evidence of alveolar hemorrhage on bronchoscopic examination or increasingly bloody returns with bronchoalveolar lavage § Observed hemoptysis § Unexplained anemia (<10 g/dL) or documented drop in hemoglobin (>1 g/dL) from less than 10g/dl § Acute respiratory distress syndrome (ARDS, according to Berlin definition)
• Provision of written informed consent by patients before any study related procedure
• Willingness and ability to comply with the protocol
• For female subjects: Confirmed post-menopausal state (defined as amenorrhea for at least 12 months)