IMLIFIDASE for ANCA-associated vasculitis|Granulomatosis with polyangiitis|Microscopic polyangiitis|Pulmonary alveolar hemorrhage|Acute respiratory distress syndrome

Inclusion criteria

• {"criterion_text":"- New or previous clinical diagnosis of ANCA-associated vasculitis, (granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) consistent with revised Chapel Hill definitions\n- ANCA titer >= 50 (AU/ml) (i.e. anti-myeloperoxidase / antiproteinase 3) no more than 14 days prior to inclusion measured by certified clinical laboratory\n- 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)\n- Provision of written informed consent by patients before any study related procedure\n- Willingness and ability to comply with the protocol\n- For female subjects: Confirmed post-menopausal state (defined as amenorrhea for at least 12 months)"}

Exclusion criteria

• {"criterion_text":"- Subjects aged < 18 or > 80 years\n- Previous treatment with imlifidase\n- Previous or ongoing high dose IVIg treatment (2 g/kg) within 28 days prior to inclusion\n- More than two plasma exchanges prior to administration of imlifidase within 28 days prior to inclusion\n- 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\n- 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\n- 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.\n- 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)\n- 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.\n- Active malignant disease or a history of malignancy within two years prior to diagnosis/infusion other than non-melanoma resected or cured skin cancer\n- Any condition that in the opinion of the investigator could increase the subject's risk by participating in the study other than those specified.\n- Subjects physically or mentally unable to give written informed consent\n- Present or history of thrombotic thrombocytopenic purpura (TTP), or known familial history of TTP\n- Subject who might be dependent on the sponsor, the investigator or the trial site.\n- Subjects deprived of freedom i.e., detainment or commitment to psychiatric ward, prison or state institution by law court or legal authority\n- Female subjects: pregnant or breastfeeding or of childbearing potential\n- Male subjects: unwilling to use double-barrier contraception for the duration of this study.\n- Concomitant autoimmunological disease (e.g. Goodpasture, vasculitis other than AAV)\n- Diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA) consistent with revised Chapel Hill definitions\n- Concomitant pulmonary disease (e.g. chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD))\n- Known allergy/sensitivity to imlifidase, IVIg and/or the respective excipients"}

Primary endpoints

• {"endpoint_text":"- ANCA seroconversion (indicated by titerbelow reference range) within 24 hours of imlifidase administration","definition_or_measurement_approach":"ANCA seroconversion defined as ANCA titer below reference range within 24 hours of imlifidase administration (measurement method not specified in the primary endpoint text)."}

Secondary endpoints

• {"endpoint_text":"- Time to ANCA seroconversion (indicated by ELISA below reference range)","definition_or_measurement_approach":"Time from treatment to ANCA seroconversion as indicated by ELISA below reference range."}
• {"endpoint_text":"- Rebound of ANCA serology greater than 50% of the initial fall in titer (i.e. rise > (ANCAmax – ANCAmin) / 2)","definition_or_measurement_approach":"ANCA rebound defined as serology rise greater than 50% of initial fall, i.e. rise > (ANCAmax – ANCAmin) / 2."}
• {"endpoint_text":"- Mortality (30 days)","definition_or_measurement_approach":"All-cause mortality within 30 days of inclusion."}
• {"endpoint_text":"- Duration of ICU stay","definition_or_measurement_approach":"Length of intensive care unit stay measured in days."}
• {"endpoint_text":"- Amelioration of lung function o Duration of invasive ventilation / ECMO o Time to resolution of ARDS (measured by Horowitz Index)","definition_or_measurement_approach":"Lung function endpoints include duration of invasive ventilation/ECMO and time to resolution of ARDS measured by Horowitz Index (PaO2/FiO2)."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Kidney function endpoints include change in KDIGO AKI staging and requirement for kidney replacement therapy dependency at 3 and 6 months."}
• {"endpoint_text":"- Safety Endpoint: Frequency and distribution of safety parameters (adverse events (AEs), severe adverse events (SAEs), clinical laboratory tests, vital signs)","definition_or_measurement_approach":"Safety assessed by frequency and distribution of AEs, SAEs, laboratory tests and vital signs."}
• {"endpoint_text":"- Safety Endpoint: Frequency and quality of infectious complications","definition_or_measurement_approach":"Infectious complications monitored and reported by frequency and quality (severity/type)."}

Germany

Earliest CTIS Part Ii Submission Date

06-09-2024

Latest Decision Or Authorization Date

21-10-2024

Processing Time Days

45

Number Of Sites

1

Number Of Participants

10

Primary sponsor

Full Name

Charite Universitaetsmedizin Berlin KöR

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Germany

Third parties

• {"country":"Germany","full_name":"Charite Universitaetsmedizin Berlin KöR","duties_or_roles":"codes:1,12,15 (DB-hosting),8","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"Charite Universitaetsmedizin Berlin KöR","duties_or_roles":"code:4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"Labor Berlin Charite Vivantes GmbH","duties_or_roles":"code:4","organisation_type":"Hospital/Clinic/Other health care facility"}