Imlifidase for the treatment of autoimmune-mediated small blood vessel inflammatio

Phase 1

Conditions: Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis with severe diffuse alveolar hemorrhage
MedDRA version: 21.1Level: PTClassification code 10072579Term: Granulomatosis with polyangiitisSystem Organ Class: 10047065 - Vascular disorders
MedDRA version: 27.0Level: PTClassification code 10063344Term: Microscopic polyangiitisSystem Organ Class: 10047065 - Vascular disorders
MedDRA version: 21.1Level: PTClassification code 10001052Term: Acute respiratory distress syndromeSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
MedDRA version: 21.1Level: LLTClassification code 10037314Term: Pulmonary alveolar hemorrhageSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Registration Number: EUCTR2021-004706-22-DE

Lead Sponsor: Charité - Universitätsmedizin Berlin

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 10

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:
oA compatible chest x-ray or CT scan (diffuse pulmonary infiltrates)
oThe absence of an alternative explanation for all pulmonary infiltrates (i.e. volume overload or pulmonary infection)
oAt 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)
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

1.Subjects aged < 18 or > 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.