Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis with severe diffuse alveolar hemorrhage MedDRA version: 21.1 Level: PT Classification code 10072579 Term: Granulomatosis with polyangiitis System Organ Class: 10047065 - Vascular disorders MedDRA version: 27.0 Level: PT Classification code 10063344 Term: Microscopic polyangiitis System Organ Class: 10047065 - Vascular disorders MedDRA version: 21.1 Level: PT Classification code 10001052 Term: Acute respiratory distress syndrome
Conditions
Interventions
Trade Name: Idefirix
Product Name: Idefirix
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: Imlifidase
Other descriptive name: Immunoglobulin G cleaving cys
Sponsors
Charité - Universitätsmedizin Berlin
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. New or previous clinical diagnosis of ANCA-associated vasculitis, (granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) consistent with revised Chapel Hill definitions 2. ANCA titer >= 50 (AU/ml) (i.e. anti-myeloperoxidase / anti-proteinase 3) no more than 14 days prior to inclusion measured by certified clinical laboratory 3. 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 (1 g/dL) from less than 10g/dl ? Acute respiratory distress syndrome (ARDS, according to Berlin definition) 4. Provision of written informed consent by patients before any study related procedure 5. Willingness and ability to comply with the protocol 6. For female subjects: Confirmed post-menopausal state (defined as amenorrhea for at least 12 months) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 10 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. Subjects aged 80 years 2. Subjects physically or mentally unable to give written informed consent 3. Subjects deprived of freedom i.e., detainment or commitment to psychiatric ward, prison or state institution by law court or legal authority 4. Female subjects: pregnant or breastfeeding or of childbearing potential 5. Male subjects: unwilling to use double-barrier contraception for the duration of this study. 6. Concomitant autoimmunological disease (e.g. Goodpasture, vasculitis other than AAV) 7. Diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA) consistent with revised Chapel Hill definitions 8. Concomitant pulmonary disease (e.g. chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD)) 9. Known allergy/sensitivity to imlifidase, IVIg and/or the respective excipients 10. Previous treatment with imlifidase 11. Previous or ongoing high dose IVIg treatment (2 g/kg) within 28 days prior to inclusion 12. More than two plasma exchanges prior to administration of imlifidase within 28 days prior to inclusion 13. 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 14. 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 15. 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. 16. 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) 17. 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. 18. Active malignant disease or a history of malignancy within two years prior to diagnosis/infusion other than non-melanoma resected or cured skin cancer 19. Any condition that in the opinion of the investigator could increase the subject's risk by participating in the study other than those specified. 20. Present or history of thrombotic thrombocytopenic purpura (TTP), or known familial history of TTP 21. Subject who might be dependent on the sponsor, the investigator or the trial site.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Define efficacy of imlifidase plus standard of care (SoC) in severe ANCA-associated vasculitis with pulmonary hemorrhage;Secondary Objective: Define impact of imlifidase plus SoC on clinical and laboratory parameters Assess safety of imlifidase plus SoC in severe ANCA-associated vasculitis with pulmonary hemorrhage ;Primary end point(s): ANCA seroconversion (indicated by titerbelow reference range) within 24 hours of imlifidase administration;Timepoint(s) of evaluation of this end point: 24 hours after Imlifidase administration | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Time to ANCA seroconversion (indicated by ELISA below reference range) • Rebound of ANCA serology greater than 50% of the initial fall in titer (i.e. rise > (ANCAmax – ANCAmin) / 2) • Mortality (30 days) • Duration of ICU stay • Amelioration of lung function o Duration of invasive ventilation / ECMO o Time to resolution of ARDS (measured by Horowitz Index) • Amelioration of kidney function o Upstaging of Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury (AKI) stages o Kidney replacement therapy-dependency at 3 and 6 months after inclusion ;Timepoint(s) of evaluation of this end point: daily for the first week, then every 2-4 days for the next 3 weeks, every 4 weeks for the next 2 months, then every 6 weeks until week 24 | — |
Countries
Germany
Contacts
Public ContactMedizinische Klinik mit Schwerpunkt
Charité - Universitätsmedizin Berlin
Outcome results
None listed