Imlifidase in ANCA-associated Vasculitis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Charite Universitaetsmedizin Berlin KöR

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

17 May 2023 → ongoing

Decision date (initial)

2024-10-21

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

The trial is co-financed by Hansa Biopharma AB. Fincancing covers all material and personell costs.

External identifiers

EU CT number

2024-516727-13-00

EudraCT number

2021-004706-22

WHO UTN

U1111-1313-0455

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

Define efficacy of imlifidase plus standard of care (SoC) in severe ANCAassociated vasculitis with pulmonary hemorrhage

Secondary objectives 2

1. Define impact of imlifidase plus SoC on clinical and laboratory parameters
2. Assess safety of imlifidase plus SoC in severe ANCA-associated vasculitis with pulmonary hemorrhage

Conditions and MedDRA coding

Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis with severe diffuse alveolar hemorrhage

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

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 / antiproteinase 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 (<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)

Exclusion criteria 21

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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. ANCA seroconversion (indicated by titerbelow reference range) within 24 hours of imlifidase administration

Secondary endpoints 8

1. Time to ANCA seroconversion (indicated by ELISA below reference range)
2. Rebound of ANCA serology greater than 50% of the initial fall in titer (i.e. rise > (ANCAmax – ANCAmin) / 2)
3. Mortality (30 days)
4. Duration of ICU stay
5. Amelioration of lung function o Duration of invasive ventilation / ECMO o Time to resolution of ARDS (measured by Horowitz Index)
6. 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
7. Safety Endpoint: Frequency and distribution of safety parameters (adverse events (AEs), severe adverse events (SAEs), clinical laboratory tests, vital signs)
8. Safety Endpoint: Frequency and quality of infectious complications

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Charite Universitaetsmedizin Berlin KöR

Sponsor organisation

Charite Universitaetsmedizin Berlin KöR

Address

Hindenburgdamm 30, Lichterfelde Lichterfelde

City

Berlin

Postcode

12203

Country

Germany

Scientific contact point

Organisation

Charite Universitaetsmedizin Berlin KöR

Contact name

Prof. Dr. med. Adrian Schreiber

Public contact point

Organisation

Charite Universitaetsmedizin Berlin KöR

Contact name

Prof. Dr. med. Adrian Schreiber

Third parties 3

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications