Open-Label Phase II Study to Evaluate the Efficacy and Safety of IdeS in Anti-GBM Disease

Number of patients without need for dialysis at 6 months. A patient with independent renal function is defined as a patient without need for dialysis.

Time frame: 6 months after dosing

Determination of anti-imlifidase antibody concentration

Time frame: Up to 6 months after dosing

Population: Some missing data at Day 50, Day 93 and Day 180

Change in proteinuria measured as u-albumin/creatinine (g/mol) in morning void during the study .

Time frame: Pre-imlifidase, 3 and 6 months after imlifidase dosing

Population: Some patients had missing data at some visits

Anti-GBM antibodies above a toxic level defined as \>20 U/mL. The level of anti-GBM antibodies was measured centrally using the Phadia ELiA(TM) anti-GBM kit. The enzyme-linked immunoassay (ELiA) is a fluorescence enzyme immunoassay.

Time frame: Predose up to 6 months after dosing

Population: Number of study visits with a toxic level are presented instead of number of patient days with an anti-GBM level \>20 U/mL as was the original plan.

Haematuria was assessed using urine dipstick. The result was presented as: Negative/Trace/+1/+2/+3/+4. In the analysis results being +2 or above are considered as relevant. Haematuria was an inclusion criterion. All 15 patients had haematuria when included in the study.

Time frame: At 6 months after dosing

Population: Data was missing for 5 of the 15 patients at 6 months.

Number of patients without need for dialysis at 3 months. A patient with independent renal function is defined as a patient without need for dialysis.

Time frame: 3 months after dosing

eGFR is a measure of kidney function. eGFR has been calculated based on p-creatinine according to the modification of diet in renal disease (MDRD) equation. eGFR for a kidney with normal function is above 90 mL/min/1.73m\^2. Reduced kidney function is characterised by a decreased eGFR value. Number of patients per 4 different eGFR categories (0-15, 15-30, 30-60, ≥60 mL/min/1.73m\^2) are presented. A shift towards a higher category during the study indicates improved renal function over time.

Time frame: Pre-imlifidase, 1, 3 and 6 months after imlifidase dosing

Population: Only patients who were alive and dialysis independent at each specific analysis time are included in this analysis because eGFR is not applicable for patients in dialysis.

Number of PLEXs needed before anti-GBM antibodies are below toxic levels. PLEX was initiated at the discretion of the investigator throughout the study.

Time frame: Pre-screening and up to Day 93 after imlifidase dosing

Imlifidase specifically cleaves all subclasses of human IgG rapidly and efficiently. The cleaving process involves two steps: (i) intact IgG to single cleaved IgG followed by (ii) single cleaved IgG to completely cleaved IgG (one F(ab')2- and one homodimeric Fc-fragment) The electroluminescence analysis method used measures the sum of intact and single cleaved IgG in serum. The efficacy of imlifidase is evaluated as remaining concentration of intact and single cleaved IgG in serum after treatment.

Time frame: Pre-dose up to 6 months after imlifidase administration

Population: Some patients had missing data at some timepoints

Area under the plasma concentration versus time curve (AUC)

Time frame: Pre-dose, 45min, 2h, 6h, 24h, Day3, Day 7, Day 10, and Day15

Clearance (CL) is a measure of the ability of the body to clear imlifidase from plasma

Time frame: Pre-dose, 45min, 2h, 6h, 24h, Day3, Day 7, Day 10, and Day15

Maximum observed plasma concentration of IdeS following dosing (Cmax)

Time frame: Pre-dose, 45min, 2h, 6h, 24h, Day3, Day 7, Day 10, and Day15

Half-life during distribution phase (Alpha-t1/2) Half-life during elimination phase (Beta-t1/2) The results refers to harmonic mean.

Time frame: Pre-dose, 45min, 2h, 6h, 24h, Day3, Day 7, Day 10, and Day15

Vz = Volume of distribution during the elimination phase

Time frame: Pre-dose, 45min, 2h, 6h, 24h, Day3, Day 7, Day 10, and Day15

Estimated glomerular filtration rate (eGFR) is a measure of kidney function. eGFR was calculated based on p-creatinine according to the modification of diet in renal disease (MDRD) equation. eGFR for a kidney with normal function is above 90 mL/min/1.73m\^2. Reduced kidney function is characterised by a decreased eGFR value.

Time frame: 3 and 6 months after imlifidase dosing

Population: Only patients who were alive and dialysis independent at respective analysis time (3 and 6 months) were included in this analysis because assessment of eGFR is not considered meaningful for patients in dialysis.

Kidney biopsies were classified according to the histopathologic classification for antineutrophil cytoplasmic antibodies (ANCA)-associated glomerulonephritis developed by Berden et al. 2010. This classification has previously been applied in a study of 123 anti-GBM disease patients (von Daalen et al 2018). Histopathologic class: * Focal (≤50% normal glomeruli) * Crescentic (≥50% glomeruli with cellular crescents) * Mixed (\<50% normal, \<50%crescentic, \<50% globally sclerotic glomeruli) * Sclerotic (≥50% globally sclerotic glomeruli) In addition information on the histological activity and kidney outcome was provided. Focal class is associated with favourable kidney outcome, whereas sclerotic carries a poor outcome. Crescentic/mixed class could have an intermediate outcome between focal and sclerotic. Immunofluorescence performed at the local hospitals was also used to assess linear IgG deposits which is a hallmark of anti-GBM antibody disease.

Time frame: Before administration of imlifidase (0-33 days) and after administration of imlifidase (3-6 days)

Population: During the study, 14 kidney biopsies were taken from 10 of the 15 included patients. 10 biopsies were taken before administration of imlifidase and 4 after administration of imlifidase.