Open-Label Phase II Study to Evaluate the Efficacy and Safety of IdeS in Anti-GBM Disease
Condition: Anti-Glomerular Basement Membrane Antibody Disease
MeSH terms: Anti-Glomerular Basement Membrane Disease
Intervention: Imlifidase
Intervention description: One dose of 0.25 mg/kg body weight imlifidase on study day 1
Intervention MeSH terms: Immunoglobulins; Immunoglobulin G
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: Open-Label, Single Arm study
Masking: None (Open Label)
Enrollment: 15.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This study will evaluate the safety and tolerability of IdeS in patients with severe
      anti-glomerular basement membrane (anti-GBM) disease receiving standard of care consisting of
      pulse-methylprednisolone, oral prednisolone and intravenous cyclophosphamide combined with
      plasma exchange (PLEX).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Anti-GBM antibodies detected by ELISA above a level that is considered toxic by the
             investigator using local laboratory. Patients double-positive for anti-GBM and
             anti-neutrophil cytoplasmic antibodies (ANCAs) may be entered in the trial, but only
             if their level of anti-GBM antibodies fulfil the criteria listed above.

          2. Estimated glomerular filtration rate (eGFR) <15 ml/min/1.73 m^2 (by modification of
             diet in renal disease (MDRD) equation) or if the patient is non-responsive to standard
             treatment, and has lost >15 ml/min/1.73 m^2 after start of treatment

          3. Haematuria on dipstick and/or urinary sediment

          4. Male or female patients aged at least 18 years; Female patients of childbearing
             potential may participate if highly effective contraception is used during the study,
             according to Clinical Trials Facilitation and Coordination Group (CTFG) guidance [18],
             see also section 4.9 (pregnancy test should be performed before inclusion).

          5. Willing and able to give written Informed Consent and to comply with the requirements
             of the study protocol; and

          6. Judged to be otherwise healthy by the Investigator, based on medical history, physical
             examination, and clinical laboratory assessments. Patients with clinical laboratory
             values that are outside of normal limits (other than those specified in the Exclusion
             Criteria) and/or with other abnormal clinical findings that are judged by the
             Investigator not to be of clinical significance, may be entered into the study.

        Exclusion Criteria:

          1. Anuria for more than 2 days (less than 200 ml during last 48 hours);

          2. Dialysis dependency for more than 5 days (maximum 3 sessions before signing informed
             consent);

          3. Ongoing moderate to severe pulmonary haemorrhage (or having ceased within the last two
             weeks), defined as requiring assisted ventilation, oxygen or blood transfusions.

          4. Pregnancy.

          5. Symptomatic congestive heart failure (NYHA class 2-4) and requiring prescription
             medication or clinically evident peripheral edema of cardiac origin;

          6. Myocardial infarction, unstable angina or stroke within 3 months prior to screening;

          7. Ongoing bacterial infection requiring antibiotic therapy or viral infection with
             Hepatitis B, C or HIV (up to 3 months old negative test results are accepted); or
             active tuberculosis as indicated by chest x-ray.

          8. Patients should not have received investigational drugs within 30 days prior to
             screening or within 4 half-lives (whichever is longer); and

          9. History or presence of any medical condition or disease which, in the opinion of the
             Investigator, may place the subject at unacceptable risk for study participation.