Trial Outcomes & Findings for Open-Label Phase II Study to Evaluate the Efficacy and Safety of IdeS in Anti-GBM Disease (NCT NCT03157037)

NCT ID: NCT03157037

Last Updated: 2022-04-07

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 15 participants
• Primary outcome timeframe: 6 months after dosing
• Results posted on: 2022-04-07

Participant Flow

Participant milestones

Measure	Treatment HMed-IdeS A single dose of IdeS (imlifidase) 0.25 mg/kg body weight (BW) intravenous infusion on study Day 1
Overall Study STARTED	15
Overall Study COMPLETED	14
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure	Treatment HMed-IdeS A single dose of IdeS (imlifidase) 0.25 mg/kg body weight (BW) intravenous infusion on study Day 1
Overall Study Death	1

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Imlifidase n=15 Participants IdeS intravenous infusion 0.25 mg/kg body weight (BW) intravenous infusion HMed-IdeS: One dose of 0.25 mg/kg BW HMed-IdeS on study day 1
Age, Continuous	61 years n=15 Participants
Sex: Female, Male Female	6 Participants n=15 Participants
Sex: Female, Male Male	9 Participants n=15 Participants
Region of Enrollment Sweden	4 participants n=15 Participants
Region of Enrollment Austria	2 participants n=15 Participants
Region of Enrollment Czechia	1 participants n=15 Participants
Region of Enrollment Denmark	3 participants n=15 Participants
Region of Enrollment France	5 participants n=15 Participants
Dialysis status at baseline Dialysis	10 Participants n=15 Participants
Dialysis status at baseline Not on dialysis but eGFR <15 mL/min/1.73 m^2	5 Participants n=15 Participants
Time since anti-glomerular basement membrane (anti-GBM) diagnosis	2 days n=15 Participants
Anti-GBM concentration	130 U/mL n=15 Participants
Time since first renal symptom	10 days n=15 Participants
Occurrence of pulmonary symptom Yes	9 Participants n=15 Participants
Occurrence of pulmonary symptom No	3 Participants n=15 Participants
Occurrence of pulmonary symptom Not reported	3 Participants n=15 Participants
Time since first pulmonary symptom	32 days n=15 Participants
Double positive Anti-GBM and antineutrophil cytoplasmic antibodies (ANCA) Yes	6 Participants n=15 Participants
Double positive Anti-GBM and antineutrophil cytoplasmic antibodies (ANCA) No	9 Participants n=15 Participants

PRIMARY outcome

Timeframe: 6 months after dosing

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.

Outcome measures

Measure	Dialysis Dependent at Baseline n=10 Participants Patients who were dialysis dependent at baseline	Dialysis Independent at Baseline n=5 Participants Patients who were dialysis independent at baseline	All Patients n=15 Participants All patients (i.e., both patients who were dialysis dependent and patients who were dialysis independent at baseline)
Number of Patients With Independent Renal Function at 6 Months	5 Participants	5 Participants	10 Participants

SECONDARY outcome

Timeframe: 3 months after dosing

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.

Outcome measures

Measure	Dialysis Dependent at Baseline n=10 Participants Patients who were dialysis dependent at baseline	Dialysis Independent at Baseline n=5 Participants Patients who were dialysis independent at baseline	All Patients n=15 Participants All patients (i.e., both patients who were dialysis dependent and patients who were dialysis independent at baseline)
Number of Patients With Independent Renal Function at 3 Months	4 Participants	5 Participants	9 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Dialysis Dependent at Baseline n=5 Participants Patients who were dialysis dependent at baseline	Dialysis Independent at Baseline n=5 Participants Patients who were dialysis independent at baseline	All Patients n=10 Participants All patients (i.e., both patients who were dialysis dependent and patients who were dialysis independent at baseline)
Renal Function at 3 and 6 Months eGFR at 3 months	20.3 mL/min/1.73m^2 Standard Deviation 4.7	26.5 mL/min/1.73m^2 Standard Deviation 11.0	23.8 mL/min/1.73m^2 Standard Deviation 8.9
Renal Function at 3 and 6 Months eGFR at 6 months	24.8 mL/min/1.73m^2 Standard Deviation 6.6	36.9 mL/min/1.73m^2 Standard Deviation 17.3	30.9 mL/min/1.73m^2 Standard Deviation 13.9

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Dialysis Dependent at Baseline n=5 Participants Patients who were dialysis dependent at baseline	Dialysis Independent at Baseline n=5 Participants Patients who were dialysis independent at baseline	All Patients n=10 Participants All patients (i.e., both patients who were dialysis dependent and patients who were dialysis independent at baseline)
Number of Patients With Renal Function Over Time Stratified by Ranges of eGFR Pre-imlifidase · eGFR (0-15)	1 Participants	5 Participants	6 Participants
Number of Patients With Renal Function Over Time Stratified by Ranges of eGFR Pre-imlifidase · eGFR (15-30)	0 Participants	0 Participants	0 Participants
Number of Patients With Renal Function Over Time Stratified by Ranges of eGFR Pre-imlifidase · eGFR (30-60)	0 Participants	0 Participants	0 Participants
Number of Patients With Renal Function Over Time Stratified by Ranges of eGFR Pre-imlifidase · eGFR (≥60)	0 Participants	0 Participants	0 Participants
Number of Patients With Renal Function Over Time Stratified by Ranges of eGFR Month 1 · eGFR (0-15)	1 Participants	1 Participants	2 Participants
Number of Patients With Renal Function Over Time Stratified by Ranges of eGFR Month 1 · eGFR (15-30)	1 Participants	2 Participants	3 Participants
Number of Patients With Renal Function Over Time Stratified by Ranges of eGFR Month 1 · eGFR (30-60)	0 Participants	2 Participants	2 Participants
Number of Patients With Renal Function Over Time Stratified by Ranges of eGFR Month 1 · eGFR (≥60)	0 Participants	0 Participants	0 Participants
Number of Patients With Renal Function Over Time Stratified by Ranges of eGFR Month 3 · eGFR (0-15)	0 Participants	0 Participants	0 Participants
Number of Patients With Renal Function Over Time Stratified by Ranges of eGFR Month 3 · eGFR (15-30)	3 Participants	3 Participants	6 Participants
Number of Patients With Renal Function Over Time Stratified by Ranges of eGFR Month 3 · eGFR (30-60)	0 Participants	1 Participants	1 Participants
Number of Patients With Renal Function Over Time Stratified by Ranges of eGFR Month 3 · eGFR (≥60)	0 Participants	0 Participants	0 Participants
Number of Patients With Renal Function Over Time Stratified by Ranges of eGFR Month 6 · eGFR (0-15)	0 Participants	0 Participants	0 Participants
Number of Patients With Renal Function Over Time Stratified by Ranges of eGFR Month 6 · eGFR (15-30)	4 Participants	2 Participants	6 Participants
Number of Patients With Renal Function Over Time Stratified by Ranges of eGFR Month 6 · eGFR (30-60)	1 Participants	3 Participants	4 Participants
Number of Patients With Renal Function Over Time Stratified by Ranges of eGFR Month 6 · eGFR (≥60)	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Dialysis Dependent at Baseline n=10 Participants Patients who were dialysis dependent at baseline	Dialysis Independent at Baseline n=5 Participants Patients who were dialysis independent at baseline	All Patients n=15 Participants All patients (i.e., both patients who were dialysis dependent and patients who were dialysis independent at baseline)
Number of Patients With Anti-GBM Antibodies Above a Toxic Level Stratified by Number of Study Visits 0 visits	1 participants	1 participants	2 participants
Number of Patients With Anti-GBM Antibodies Above a Toxic Level Stratified by Number of Study Visits 1 visit	3 participants	4 participants	7 participants
Number of Patients With Anti-GBM Antibodies Above a Toxic Level Stratified by Number of Study Visits 2 visits	1 participants	0 participants	1 participants
Number of Patients With Anti-GBM Antibodies Above a Toxic Level Stratified by Number of Study Visits 3 visits	1 participants	0 participants	1 participants
Number of Patients With Anti-GBM Antibodies Above a Toxic Level Stratified by Number of Study Visits 5 visits	2 participants	0 participants	2 participants
Number of Patients With Anti-GBM Antibodies Above a Toxic Level Stratified by Number of Study Visits 6 visits	1 participants	0 participants	1 participants
Number of Patients With Anti-GBM Antibodies Above a Toxic Level Stratified by Number of Study Visits 9 visits	1 participants	0 participants	1 participants

SECONDARY outcome

Timeframe: At 6 months after dosing

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

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.

Outcome measures

Measure	Dialysis Dependent at Baseline n=10 Participants Patients who were dialysis dependent at baseline	Dialysis Independent at Baseline Patients who were dialysis independent at baseline	All Patients All patients (i.e., both patients who were dialysis dependent and patients who were dialysis independent at baseline)
Number of Patients With Haematuria (Blood in Urine)	3 Patients with haematuria (+2 or above)	—	—

SECONDARY outcome

Timeframe: Pre-imlifidase, 3 and 6 months after imlifidase dosing

Population: Some patients had missing data at some visits

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

Outcome measures

Measure	Dialysis Dependent at Baseline n=10 Participants Patients who were dialysis dependent at baseline	Dialysis Independent at Baseline n=5 Participants Patients who were dialysis independent at baseline	All Patients n=15 Participants All patients (i.e., both patients who were dialysis dependent and patients who were dialysis independent at baseline)
Change in Proteinuria During the Study Pre-imlifidase	1117 g/mol Standard Deviation 1544	199 g/mol Standard Deviation 166	700 g/mol Standard Deviation 1197
Change in Proteinuria During the Study 3 months	220 g/mol Standard Deviation 197	153 g/mol Standard Deviation 172	190 g/mol Standard Deviation 178
Change in Proteinuria During the Study 6 months	183 g/mol Standard Deviation 231	122 g/mol Standard Deviation 133	161 g/mol Standard Deviation 198

SECONDARY outcome

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

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

Outcome measures

Measure	Dialysis Dependent at Baseline n=10 Participants Patients who were dialysis dependent at baseline	Dialysis Independent at Baseline n=5 Participants Patients who were dialysis independent at baseline	All Patients n=15 Participants All patients (i.e., both patients who were dialysis dependent and patients who were dialysis independent at baseline)
Number of PLEXs Needed Over Time Day 22 to Day 29	5 Number of PLEX performed	1 Number of PLEX performed	6 Number of PLEX performed
Number of PLEXs Needed Over Time Pre-Screening	10 Number of PLEX performed	23 Number of PLEX performed	33 Number of PLEX performed
Number of PLEXs Needed Over Time Post-Screening to pre-imlifidase dose	5 Number of PLEX performed	0 Number of PLEX performed	5 Number of PLEX performed
Number of PLEXs Needed Over Time Pre-imlifidase to Day 3	0 Number of PLEX performed	1 Number of PLEX performed	1 Number of PLEX performed
Number of PLEXs Needed Over Time Day 3 to Day 7	8 Number of PLEX performed	0 Number of PLEX performed	8 Number of PLEX performed
Number of PLEXs Needed Over Time Day 7 to Day 10	14 Number of PLEX performed	0 Number of PLEX performed	14 Number of PLEX performed
Number of PLEXs Needed Over Time Day 10 to Day 15	20 Number of PLEX performed	2 Number of PLEX performed	22 Number of PLEX performed
Number of PLEXs Needed Over Time Day 15 to Day 22	18 Number of PLEX performed	5 Number of PLEX performed	23 Number of PLEX performed
Number of PLEXs Needed Over Time Day 29 to Day 50	5 Number of PLEX performed	3 Number of PLEX performed	8 Number of PLEX performed
Number of PLEXs Needed Over Time Day 50 to Day 93	0 Number of PLEX performed	1 Number of PLEX performed	1 Number of PLEX performed
Number of PLEXs Needed Over Time Total (post-imlifidase to Day 93)	70 Number of PLEX performed	13 Number of PLEX performed	83 Number of PLEX performed
Number of PLEXs Needed Over Time Total (pre-screening to Day 93)	85 Number of PLEX performed	36 Number of PLEX performed	121 Number of PLEX performed

SECONDARY outcome

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

Maximum observed plasma concentration of IdeS following dosing (Cmax)

Outcome measures

Measure	Dialysis Dependent at Baseline n=15 Participants Patients who were dialysis dependent at baseline	Dialysis Independent at Baseline Patients who were dialysis independent at baseline	All Patients All patients (i.e., both patients who were dialysis dependent and patients who were dialysis independent at baseline)
Pharmacokinetics of Imlifidase (Cmax)	4.7 µg/mL Interval 2.6 to 8.0	—	—

SECONDARY outcome

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

Area under the plasma concentration versus time curve (AUC)

Outcome measures

Measure	Dialysis Dependent at Baseline n=15 Participants Patients who were dialysis dependent at baseline	Dialysis Independent at Baseline Patients who were dialysis independent at baseline	All Patients All patients (i.e., both patients who were dialysis dependent and patients who were dialysis independent at baseline)
Pharmacokinetics of Imlifidase (AUC)	158 h*µg/mL Interval 73.0 to 304.0	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Dialysis Dependent at Baseline n=15 Participants Patients who were dialysis dependent at baseline	Dialysis Independent at Baseline Patients who were dialysis independent at baseline	All Patients All patients (i.e., both patients who were dialysis dependent and patients who were dialysis independent at baseline)
Pharmacokinetics of Imlifidase (t1/2) Alpha-t1/2	2.6 h Interval 0.9 to 7.5	—	—
Pharmacokinetics of Imlifidase (t1/2) Beta-t1/2	53 h Interval 26.0 to 115.0	—	—

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	Dialysis Dependent at Baseline n=15 Participants Patients who were dialysis dependent at baseline	Dialysis Independent at Baseline Patients who were dialysis independent at baseline	All Patients All patients (i.e., both patients who were dialysis dependent and patients who were dialysis independent at baseline)
Pharmacokinetics of Imlifidase (CL)	1.6 mL/h/kg Interval 0.8 to 3.4	—	—

SECONDARY outcome

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

Vz = Volume of distribution during the elimination phase

Outcome measures

Measure	Dialysis Dependent at Baseline n=15 Participants Patients who were dialysis dependent at baseline	Dialysis Independent at Baseline Patients who were dialysis independent at baseline	All Patients All patients (i.e., both patients who were dialysis dependent and patients who were dialysis independent at baseline)
Pharmacokinetics of Imlifidase (Vz)	0.13 L/kg Interval 0.07 to 0.21	—	—

SECONDARY outcome

Timeframe: Pre-dose up to 6 months after imlifidase administration

Population: Some patients had missing data at some timepoints

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.

Outcome measures

Measure	Dialysis Dependent at Baseline n=15 Participants Patients who were dialysis dependent at baseline	Dialysis Independent at Baseline Patients who were dialysis independent at baseline	All Patients All patients (i.e., both patients who were dialysis dependent and patients who were dialysis independent at baseline)
Pharmacodynamics (IgG Degradation Measured as Remaining Concentration of Intact and Single Cleaved IgG) Pre-dose	6.66 mg/mL Standard Deviation 2.94	—	—
Pharmacodynamics (IgG Degradation Measured as Remaining Concentration of Intact and Single Cleaved IgG) 2 hours	0.17 mg/mL Standard Deviation 0.12	—	—
Pharmacodynamics (IgG Degradation Measured as Remaining Concentration of Intact and Single Cleaved IgG) 6 hours	0.08 mg/mL Standard Deviation 0.05	—	—
Pharmacodynamics (IgG Degradation Measured as Remaining Concentration of Intact and Single Cleaved IgG) 24 hours	0.08 mg/mL Standard Deviation 0.05	—	—
Pharmacodynamics (IgG Degradation Measured as Remaining Concentration of Intact and Single Cleaved IgG) Day 3	0.09 mg/mL Standard Deviation 0.05	—	—
Pharmacodynamics (IgG Degradation Measured as Remaining Concentration of Intact and Single Cleaved IgG) Day 7	0.85 mg/mL Standard Deviation 1.56	—	—
Pharmacodynamics (IgG Degradation Measured as Remaining Concentration of Intact and Single Cleaved IgG) Day 10	1.58 mg/mL Standard Deviation 1.69	—	—
Pharmacodynamics (IgG Degradation Measured as Remaining Concentration of Intact and Single Cleaved IgG) Day 15	2.64 mg/mL Standard Deviation 2.42	—	—
Pharmacodynamics (IgG Degradation Measured as Remaining Concentration of Intact and Single Cleaved IgG) Day 22	2.94 mg/mL Standard Deviation 2.34	—	—
Pharmacodynamics (IgG Degradation Measured as Remaining Concentration of Intact and Single Cleaved IgG) Day 29	3.94 mg/mL Standard Deviation 2.18	—	—
Pharmacodynamics (IgG Degradation Measured as Remaining Concentration of Intact and Single Cleaved IgG) Day 50	4.29 mg/mL Standard Deviation 2.05	—	—
Pharmacodynamics (IgG Degradation Measured as Remaining Concentration of Intact and Single Cleaved IgG) Day 180	6.76 mg/mL Standard Deviation 2.49	—	—

SECONDARY outcome

Timeframe: Up to 6 months after dosing

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

Determination of anti-imlifidase antibody concentration

Outcome measures

Measure	Dialysis Dependent at Baseline n=15 Participants Patients who were dialysis dependent at baseline	Dialysis Independent at Baseline Patients who were dialysis independent at baseline	All Patients All patients (i.e., both patients who were dialysis dependent and patients who were dialysis independent at baseline)
Anti-imlifidase Antibodies (ADA) Pre-imlifidase	9.00 mg/L Standard Deviation 4.17	—	—
Anti-imlifidase Antibodies (ADA) Day 7	4.32 mg/L Standard Deviation 5.29	—	—
Anti-imlifidase Antibodies (ADA) Day 15	752 mg/L Standard Deviation 728	—	—
Anti-imlifidase Antibodies (ADA) Day 22	744 mg/L Standard Deviation 736	—	—
Anti-imlifidase Antibodies (ADA) Day 29	609 mg/L Standard Deviation 493	—	—
Anti-imlifidase Antibodies (ADA) Day 50	547 mg/L Standard Deviation 580	—	—
Anti-imlifidase Antibodies (ADA) Day 93	327 mg/L Standard Deviation 263	—	—
Anti-imlifidase Antibodies (ADA) Day 180	242 mg/L Standard Deviation 280	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Dialysis Dependent at Baseline n=14 Biopsies Patients who were dialysis dependent at baseline	Dialysis Independent at Baseline Patients who were dialysis independent at baseline	All Patients All patients (i.e., both patients who were dialysis dependent and patients who were dialysis independent at baseline)
Renal Histology Crescentic	9 Biopsies	—	—
Renal Histology Linear IgG deposits	11 Biopsies	—	—
Renal Histology Mixed	4 Biopsies	—	—
Renal Histology Sclerotic	1 Biopsies	—	—

Adverse Events

Safety Analysis Set

Serious events: 5 serious events

Other events: 15 other events

Deaths: 1 deaths

Serious adverse events

Measure	Safety Analysis Set n=15 participants at risk All patients who have received imlifidase.
Gastrointestinal disorders Diarrhea	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Gastrointestinal disorders Vomiting	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
General disorders Pyrexia	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Infections and infestations Viral infection	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Infections and infestations Pneumonia	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Metabolism and nutrition disorders Dehydration	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Cardiac disorders Cardiac failure	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Musculoskeletal and connective tissue disorders Back pain	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).

Other adverse events

Measure	Safety Analysis Set n=15 participants at risk All patients who have received imlifidase.
Blood and lymphatic system disorders Anaemia	40.0% 6/15 • Number of events 6 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Ear and labyrinth disorders Tinnitus	13.3% 2/15 • Number of events 3 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Eye disorders Foreign body sensation in eyes	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Gastrointestinal disorders Diarrhoea	13.3% 2/15 • Number of events 2 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Gastrointestinal disorders Nausea	26.7% 4/15 • Number of events 4 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Gastrointestinal disorders Vomiting	13.3% 2/15 • Number of events 2 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
General disorders Fatigue	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Immune system disorders Cryoglobulinaemia	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Immune system disorders Hypogammaglobulinaemia	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Infections and infestations Clostridium difficile infection	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Infections and infestations Herpes zoster	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Infections and infestations Pneumonia klebsiella	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Infections and infestations Urinary tract infection	13.3% 2/15 • Number of events 2 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Investigations Blood iron decreased	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Investigations Red blood cell count decreased	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Metabolism and nutrition disorders Decreased appetite	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Metabolism and nutrition disorders Hyperglycaemia	13.3% 2/15 • Number of events 2 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Metabolism and nutrition disorders Hyperphosphataemia	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Metabolism and nutrition disorders Steroid diabetes	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Musculoskeletal and connective tissue disorders Arthralgia	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Musculoskeletal and connective tissue disorders Muscle spasms	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Nervous system disorders Cognitive disorder	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Nervous system disorders Dizziness	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Nervous system disorders Headache	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Renal and urinary disorders Haematuria	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Respiratory, thoracic and mediastinal disorders Bronchial obstruction	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Respiratory, thoracic and mediastinal disorders Dyspnoea	6.7% 1/15 • Number of events 2 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Skin and subcutaneous tissue disorders Ecchymosis	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Skin and subcutaneous tissue disorders Hyperhidrosis	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Skin and subcutaneous tissue disorders Rash erythematous	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Skin and subcutaneous tissue disorders Urticaria	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Vascular disorders Hypertension	20.0% 3/15 • Number of events 3 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Vascular disorders Pelvic venous thrombosis	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Vascular disorders Thrombophlebitis	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Respiratory, thoracic and mediastinal disorders Sinus pain	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Blood and lymphatic system disorders Leukopenia	13.3% 2/15 • Number of events 2 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Blood and lymphatic system disorders Lymphopenia	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Blood and lymphatic system disorders Thrombocytopenia	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Eye disorders Vision blurred	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Gastrointestinal disorders Mouth ulceration	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Gastrointestinal disorders Rectal haemorrhage	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
General disorders Influenza like illness	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
General disorders Chest discomfort	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Infections and infestations Nasopharyngitis	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Infections and infestations Cystitis	6.7% 1/15 • Number of events 3 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Infections and infestations Clostridium difficile colitis	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Infections and infestations Gastroenteritis	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Injury, poisoning and procedural complications Humerus fracture	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Injury, poisoning and procedural complications Fall	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Injury, poisoning and procedural complications Limb injury	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Investigations Anti-glomerular basement membrane antibody positive	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Investigations Borrelia test positive	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Metabolism and nutrition disorders Hypoglycaemia	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Metabolism and nutrition disorders Hyperkalaemia	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Musculoskeletal and connective tissue disorders Back pain	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Musculoskeletal and connective tissue disorders Tendon pain	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lipoma	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Nervous system disorders Post herpetic neuralgia	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Reproductive system and breast disorders Menorrhagia	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Skin and subcutaneous tissue disorders Dermatitis allergic	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).
Vascular disorders Deep vein thrombosis	6.7% 1/15 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the patient signed the informed consent form (ICF) until end of study. A treatment emergent adverse event (TEAE) is defined as any AE occurring after imlifidase administration and within the time of the residual drug effect period (i.e. 28 days after admin). Data on AEs were obtained if spontaneously reported, if reported in response to an open question, or if revealed by observation. All Serious Adverse Events (SAEs) were post-TEAEs and those are listed in the "SAE" table. "Other (Not Including Serious) Adverse Events" presents all reported AEs in the study (47 TEAEs and 35 post-TEAEs).

Additional Information

Professor Mårten Segelmark

Linköping University

Phone: +46 70 287 19 44

Email: marten.segelmark@liu.se

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place