Trial Outcomes & Findings for An Efficacy and Safety Study of Imlifidase in Treatment of Antibody-Mediated Rejection in Kidney Transplant Patients (NCT NCT03897205)

NCT ID: NCT03897205

Last Updated: 2024-02-28

Results Overview

Maximum reduction (%) in the sum of DSA at any time point during the 5 days following the start of treatment. Only DSA with ≥1000 mean fluorescence intensity (MFI) at pre-treatment were included in the calculations. Clarification: The higher the maximum reduction percentage the lower the remaining DSA level.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 30 participants
• Primary outcome timeframe: Start of treatment until 5 days following start of treatment
• Results posted on: 2024-02-28

Participant Flow

Participant milestones

Measure	Imlifidase Participants randomized to imlifidase	Plasma Exchange Participants randomized to plasma exchange
Overall Study STARTED	19	10
Overall Study COMPLETED	17	10
Overall Study NOT COMPLETED	2	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

An Efficacy and Safety Study of Imlifidase in Treatment of Antibody-Mediated Rejection in Kidney Transplant Patients

Baseline characteristics by cohort

Measure	Imlifidase n=19 Participants Participants randomized to imlifidase	Plasma Exchange n=10 Participants Participants randomized to plasma exchange	Total n=29 Participants Total of all reporting groups
Age, Continuous	43.7 years STANDARD_DEVIATION 13.7 • n=5 Participants	52.8 years STANDARD_DEVIATION 16.4 • n=7 Participants	46.8 years STANDARD_DEVIATION 15.0 • n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	5 Participants n=7 Participants	13 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	5 Participants n=7 Participants	16 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants	0 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) White	14 Participants n=5 Participants	9 Participants n=7 Participants	23 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Austria	1 participants n=5 Participants	3 participants n=7 Participants	4 participants n=5 Participants
Region of Enrollment United States	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants
Region of Enrollment France	10 participants n=5 Participants	3 participants n=7 Participants	13 participants n=5 Participants
Region of Enrollment Australia	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Region of Enrollment Germany	5 participants n=5 Participants	3 participants n=7 Participants	8 participants n=5 Participants

PRIMARY outcome

Timeframe: Start of treatment until 5 days following start of treatment

Population: Participants with MFI values less than 1000 were excluded from the analysis

Maximum reduction (%) in the sum of DSA at any time point during the 5 days following the start of treatment.

Only DSA with ≥1000 mean fluorescence intensity (MFI) at pre-treatment were included in the calculations.

Clarification: The higher the maximum reduction percentage the lower the remaining DSA level.

Outcome measures

Measure	Imlifidase n=18 Participants Participants randomized to imlifidase	Plasma Exchange n=8 Participants Participants randomized to plasma exchange
Maximum Reduction in Donor Specific Antibodies (DSA) Level During the 5 Days Following the Start of Treatment	94 percentage of maximum DSA reduction Standard Deviation 4	36 percentage of maximum DSA reduction Standard Deviation 26

SECONDARY outcome

Timeframe: Screening until Day 180

DSA levels were assessed at all visits throughout the study. The results are presented as reduction (%) from baseline. Clarification: The higher the reduction percentage the lower the remaining DSA level. Please observe that a negative reduction value represents an increase in DSA level from baseline.

Outcome measures

Measure	Imlifidase n=18 Participants Participants randomized to imlifidase	Plasma Exchange n=8 Participants Participants randomized to plasma exchange
Reduction in DSA Levels After Treatment 6 hours	94 percentage of DSA reduction Standard Deviation 4	-2 percentage of DSA reduction Standard Deviation 33
Reduction in DSA Levels After Treatment 24 hours	92 percentage of DSA reduction Standard Deviation 5	0 percentage of DSA reduction Standard Deviation 25
Reduction in DSA Levels After Treatment 48 hours	89 percentage of DSA reduction Standard Deviation 10	18 percentage of DSA reduction Standard Deviation 34
Reduction in DSA Levels After Treatment 72 hours	83 percentage of DSA reduction Standard Deviation 24	10 percentage of DSA reduction Standard Deviation 32
Reduction in DSA Levels After Treatment Day 8	33 percentage of DSA reduction Standard Deviation 45	39 percentage of DSA reduction Standard Deviation 20
Reduction in DSA Levels After Treatment Day 11	35 percentage of DSA reduction Standard Deviation 34	22 percentage of DSA reduction Standard Deviation 34
Reduction in DSA Levels After Treatment Day 15	31 percentage of DSA reduction Standard Deviation 43	28 percentage of DSA reduction Standard Deviation 36
Reduction in DSA Levels After Treatment Day 22	28 percentage of DSA reduction Standard Deviation 46	23 percentage of DSA reduction Standard Deviation 34
Reduction in DSA Levels After Treatment Day 29	35 percentage of DSA reduction Standard Deviation 30	30 percentage of DSA reduction Standard Deviation 14
Reduction in DSA Levels After Treatment Day 64	30 percentage of DSA reduction Standard Deviation 38	32 percentage of DSA reduction Standard Deviation 34
Reduction in DSA Levels After Treatment Day 90	25 percentage of DSA reduction Standard Deviation 41	41 percentage of DSA reduction Standard Deviation 33
Reduction in DSA Levels After Treatment Day 180	29 percentage of DSA reduction Standard Deviation 38	35 percentage of DSA reduction Standard Deviation 32
Reduction in DSA Levels After Treatment 2 hours	91 percentage of DSA reduction Standard Deviation 7	-2 percentage of DSA reduction Standard Deviation 28
Reduction in DSA Levels After Treatment 96 hours	58 percentage of DSA reduction Standard Deviation 32	22 percentage of DSA reduction Standard Deviation 26
Reduction in DSA Levels After Treatment Day 6	41 percentage of DSA reduction Standard Deviation 42	31 percentage of DSA reduction Standard Deviation 23

SECONDARY outcome

Timeframe: Screening until Day 180

Population: Some patients had missing values at sporadic occasions.

eGFR as calculated from p-creatinine is a measure of kidney function. eGFR was assessed at all visits throughout the study.

Outcome measures

Measure	Imlifidase n=19 Participants Participants randomized to imlifidase	Plasma Exchange n=10 Participants Participants randomized to plasma exchange
Estimated Glomerular Filtration Rate (eGFR) Levels Day 15	32.1 mL/min/1.73m2 Standard Deviation 19.3	31.1 mL/min/1.73m2 Standard Deviation 15.4
Estimated Glomerular Filtration Rate (eGFR) Levels Day 22	29.8 mL/min/1.73m2 Standard Deviation 16.7	31.9 mL/min/1.73m2 Standard Deviation 14.8
Estimated Glomerular Filtration Rate (eGFR) Levels Day 29	27.5 mL/min/1.73m2 Standard Deviation 15.3	31.7 mL/min/1.73m2 Standard Deviation 14.5
Estimated Glomerular Filtration Rate (eGFR) Levels Day 64	29.4 mL/min/1.73m2 Standard Deviation 14.9	34.6 mL/min/1.73m2 Standard Deviation 14.5
Estimated Glomerular Filtration Rate (eGFR) Levels Pre-dose	28.0 mL/min/1.73m2 Standard Deviation 14.0	21.0 mL/min/1.73m2 Standard Deviation 8.1
Estimated Glomerular Filtration Rate (eGFR) Levels 24 hours	25.8 mL/min/1.73m2 Standard Deviation 13.8	23.5 mL/min/1.73m2 Standard Deviation 11.0
Estimated Glomerular Filtration Rate (eGFR) Levels 48 hours	26.2 mL/min/1.73m2 Standard Deviation 14.5	25.7 mL/min/1.73m2 Standard Deviation 9.4
Estimated Glomerular Filtration Rate (eGFR) Levels 72 hours	27.6 mL/min/1.73m2 Standard Deviation 15.9	27.2 mL/min/1.73m2 Standard Deviation 10.8
Estimated Glomerular Filtration Rate (eGFR) Levels 96 hours	30.6 mL/min/1.73m2 Standard Deviation 19.5	30.5 mL/min/1.73m2 Standard Deviation 13.8
Estimated Glomerular Filtration Rate (eGFR) Levels Day 6	30.3 mL/min/1.73m2 Standard Deviation 18.6	31.2 mL/min/1.73m2 Standard Deviation 12.9
Estimated Glomerular Filtration Rate (eGFR) Levels Day 8	33.4 mL/min/1.73m2 Standard Deviation 21.1	36.2 mL/min/1.73m2 Standard Deviation 18.2
Estimated Glomerular Filtration Rate (eGFR) Levels Day 11	32.2 mL/min/1.73m2 Standard Deviation 18.9	34.0 mL/min/1.73m2 Standard Deviation 16.6
Estimated Glomerular Filtration Rate (eGFR) Levels Day 90	27.2 mL/min/1.73m2 Standard Deviation 16.7	31.6 mL/min/1.73m2 Standard Deviation 12.8
Estimated Glomerular Filtration Rate (eGFR) Levels Day 180	29.9 mL/min/1.73m2 Standard Deviation 15.5	32.5 mL/min/1.73m2 Standard Deviation 17.8

SECONDARY outcome

Timeframe: Pre-dose until Day 180

Population: Some patients had missing data at different occasions during the study.

The albumine/creatinine ratio in urine is a measure of kidney function.

Outcome measures

Measure	Imlifidase n=19 Participants Participants randomized to imlifidase	Plasma Exchange n=10 Participants Participants randomized to plasma exchange
Urine Albumine/Creatinine Ratio Pre-dose	626 mg/g Standard Deviation 972	134 mg/g Standard Deviation 165
Urine Albumine/Creatinine Ratio Day 90	669 mg/g Standard Deviation 964	119 mg/g Standard Deviation 166
Urine Albumine/Creatinine Ratio Day 180	815 mg/g Standard Deviation 1018	242 mg/g Standard Deviation 295

SECONDARY outcome

Timeframe: Screening until Day 180

Information on patients who experienced graft loss was collected throughout the study.

Outcome measures

Measure	Imlifidase n=19 Participants Participants randomized to imlifidase	Plasma Exchange n=10 Participants Participants randomized to plasma exchange
Number of Patients With Graft Loss Within 180 Days of Treatment	5 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 180

Biopsies collected 180 days after treatment were analysed for signs of glomerulopathy.

Outcome measures

Measure	Imlifidase n=19 Participants Participants randomized to imlifidase	Plasma Exchange n=10 Participants Participants randomized to plasma exchange
Number of Patients With Signs or no Signs of Transplant Glomerulopathy at Day 180 Patiens with no biopsy result or no evaluable biopsy result	4 Participants	0 Participants
Number of Patients With Signs or no Signs of Transplant Glomerulopathy at Day 180 Patients with no signs of transplant glomerulopathy	7 Participants	4 Participants
Number of Patients With Signs or no Signs of Transplant Glomerulopathy at Day 180 Patients with signs of transplant glomerulopathy	8 Participants	6 Participants

SECONDARY outcome

Timeframe: Screening, Day 29 and Day 180

Kidney biopsies were assessed according to the Banff (2017) criteria at screening (baseline), Day 29, and Day 180.

Abbreviations: AMR=Antibody mediated rejection, CMR=cell-mediated rejection

Outcome measures

Measure	Imlifidase n=19 Participants Participants randomized to imlifidase	Plasma Exchange n=10 Participants Participants randomized to plasma exchange
Number of Patients With Different Types of Kidney Histopathology Throughout the Trial Screening · Active AMR	7 Participants	4 Participants
Number of Patients With Different Types of Kidney Histopathology Throughout the Trial Screening · Active AMR + Borderline CMR	0 Participants	1 Participants
Number of Patients With Different Types of Kidney Histopathology Throughout the Trial Screening · Active AMR + CMR	5 Participants	1 Participants
Number of Patients With Different Types of Kidney Histopathology Throughout the Trial Screening · Chronic Active AMR + Borderline CMR	3 Participants	1 Participants
Number of Patients With Different Types of Kidney Histopathology Throughout the Trial Screening · CMR	0 Participants	0 Participants
Number of Patients With Different Types of Kidney Histopathology Throughout the Trial Screening · No rejection	0 Participants	0 Participants
Number of Patients With Different Types of Kidney Histopathology Throughout the Trial Day 29 · Chronic Active AMR	4 Participants	2 Participants
Number of Patients With Different Types of Kidney Histopathology Throughout the Trial Day 29 · No rejection	5 Participants	1 Participants
Number of Patients With Different Types of Kidney Histopathology Throughout the Trial Day 29 · Missing data	2 Participants	0 Participants
Number of Patients With Different Types of Kidney Histopathology Throughout the Trial Day 180 · Active AMR	2 Participants	2 Participants
Number of Patients With Different Types of Kidney Histopathology Throughout the Trial Day 180 · Active AMR + Borderline CMR	0 Participants	0 Participants
Number of Patients With Different Types of Kidney Histopathology Throughout the Trial Day 180 · Chronic Active AMR + CMR	1 Participants	0 Participants
Number of Patients With Different Types of Kidney Histopathology Throughout the Trial Day 180 · Chronic Active AMR	5 Participants	5 Participants
Number of Patients With Different Types of Kidney Histopathology Throughout the Trial Day 180 · Borderline CMR	0 Participants	0 Participants
Number of Patients With Different Types of Kidney Histopathology Throughout the Trial Day 180 · No rejection	2 Participants	2 Participants
Number of Patients With Different Types of Kidney Histopathology Throughout the Trial Day 180 · Missing data	6 Participants	0 Participants
Number of Patients With Different Types of Kidney Histopathology Throughout the Trial Screening · Chronic Active AMR + CMR	1 Participants	2 Participants
Number of Patients With Different Types of Kidney Histopathology Throughout the Trial Screening · Chronic Active AMR	3 Participants	1 Participants
Number of Patients With Different Types of Kidney Histopathology Throughout the Trial Screening · Borderline CMR	0 Participants	0 Participants
Number of Patients With Different Types of Kidney Histopathology Throughout the Trial Screening · Missing data	0 Participants	0 Participants
Number of Patients With Different Types of Kidney Histopathology Throughout the Trial Day 29 · Active AMR	4 Participants	3 Participants
Number of Patients With Different Types of Kidney Histopathology Throughout the Trial Day 29 · Active AMR + Borderline CMR	0 Participants	1 Participants
Number of Patients With Different Types of Kidney Histopathology Throughout the Trial Day 29 · Active AMR + CMR	1 Participants	1 Participants
Number of Patients With Different Types of Kidney Histopathology Throughout the Trial Day 29 · Chronic Active AMR + Borderline CMR	1 Participants	1 Participants
Number of Patients With Different Types of Kidney Histopathology Throughout the Trial Day 29 · Chronic Active AMR + CMR	1 Participants	0 Participants
Number of Patients With Different Types of Kidney Histopathology Throughout the Trial Day 29 · Borderline CMR	0 Participants	1 Participants
Number of Patients With Different Types of Kidney Histopathology Throughout the Trial Day 29 · CMR	1 Participants	0 Participants
Number of Patients With Different Types of Kidney Histopathology Throughout the Trial Day 180 · Active AMR + CMR	1 Participants	0 Participants
Number of Patients With Different Types of Kidney Histopathology Throughout the Trial Day 180 · Chronic Active AMR + Borderline CMR	2 Participants	0 Participants
Number of Patients With Different Types of Kidney Histopathology Throughout the Trial Day 180 · CMR	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Screening, Day 29, and Day 180

Kidney biopsies were taken at screening, Day 29, and Day 180. Changes from baseline in mRNA levels were assessed as evidence of resolved AMR.

Outcome measures

Measure	Imlifidase n=19 Participants Participants randomized to imlifidase	Plasma Exchange n=10 Participants Participants randomized to plasma exchange
Number of Patients With Resolved AMR as Assessed by Messenger Ribonucleic Acid (mRNA) Levels Day 180	0 Participants	0 Participants
Number of Patients With Resolved AMR as Assessed by Messenger Ribonucleic Acid (mRNA) Levels Day 29	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 1 to Day 180

Population: In total 4 patients from the imlifidase arm were treated with PE. Of these 3 patients received PE after start of IVIg. All 10 patients from the PE arm were treated with PE. Of these 1 patient received PE after start of IVIg. One (1) patient from the PE arm also received IA after start of IVIg.

Total number of administered PE and IA sessions to each treatment group are presented during the complete trial (Day 1 to Day 180) and for the time period: start of IVIg administration to Day 180.

Outcome measures

Measure	Imlifidase n=19 Participants Participants randomized to imlifidase	Plasma Exchange n=10 Participants Participants randomized to plasma exchange
Number of Administered Plasma Exchange (PE) and Immunoadsorption (IA) Sessions Number of PE administered from Day 1 to Day 180	20 Sessions	70 Sessions
Number of Administered Plasma Exchange (PE) and Immunoadsorption (IA) Sessions Number of PE administered after start of IVIg	18 Sessions	11 Sessions
Number of Administered Plasma Exchange (PE) and Immunoadsorption (IA) Sessions Number of IA administered from Day 1 to Day 180	0 Sessions	23 Sessions
Number of Administered Plasma Exchange (PE) and Immunoadsorption (IA) Sessions Number of IA administered after start of IVIg	0 Sessions	23 Sessions

SECONDARY outcome

Timeframe: Pre-dose until Day 6

Total serum IgG levels over time following treatment until administration of IVIg.

Please observe, IVIg was initiated on Day 4 (before 96 h measurement) for the imlifidase group.

Outcome measures

Measure	Imlifidase n=19 Participants Participants randomized to imlifidase	Plasma Exchange n=10 Participants Participants randomized to plasma exchange
Total Serum Immunoglobulin G (IgG) Levels Until Administration of Intravenous Immunoglobulin (IVIg) Pre-dose	8.6 mg/mL Standard Deviation 6.1	7.9 mg/mL Standard Deviation 5.5
Total Serum Immunoglobulin G (IgG) Levels Until Administration of Intravenous Immunoglobulin (IVIg) 24 hours	0.2 mg/mL Standard Deviation 0.2	5.2 mg/mL Standard Deviation 3.7
Total Serum Immunoglobulin G (IgG) Levels Until Administration of Intravenous Immunoglobulin (IVIg) 48 hours	0.2 mg/mL Standard Deviation 0.2	4.6 mg/mL Standard Deviation 4.3
Total Serum Immunoglobulin G (IgG) Levels Until Administration of Intravenous Immunoglobulin (IVIg) 96 hours	11.7 mg/mL Standard Deviation 5.4	4.1 mg/mL Standard Deviation 4.3
Total Serum Immunoglobulin G (IgG) Levels Until Administration of Intravenous Immunoglobulin (IVIg) 2 hours	0.2 mg/mL Standard Deviation 0.1	4.3 mg/mL Standard Deviation 3.5
Total Serum Immunoglobulin G (IgG) Levels Until Administration of Intravenous Immunoglobulin (IVIg) 6 hours	0.2 mg/mL Standard Deviation 0.1	4.6 mg/mL Standard Deviation 3.6
Total Serum Immunoglobulin G (IgG) Levels Until Administration of Intravenous Immunoglobulin (IVIg) 72 hours	0.5 mg/mL Standard Deviation 0.8	4.8 mg/mL Standard Deviation 4.3
Total Serum Immunoglobulin G (IgG) Levels Until Administration of Intravenous Immunoglobulin (IVIg) Day 6	20.0 mg/mL Standard Deviation 8.4	4.2 mg/mL Standard Deviation 4.5

SECONDARY outcome

Timeframe: Start of treatment (Day 1) up to administration of IVIg on Day 4 (imlifidase group) and until administration of IVIg within Day 15 (PE group)

Population: IVIg was administered on Day 4 (before 96 h measurement) to patients treated with imlifidase. Hence measurement of intact IgG was not performed for this group from 96 hours onwards. Measurement was stopped for PE patients when IVIg was administered.

Presence of IgG, scIgG, and F(ab')2 was analysed using sodium dodecyl-sulphate polyacrylamide gel electrophoresis (SDS-PAGE)/western blot.

Of note, IVIg was administered on Day 4 (before 96 h measurement) to patients treated with imlifidase. Hence no analyses beyond this timepoint were performed for this group.

Outcome measures

Measure	Imlifidase n=19 Participants Participants randomized to imlifidase	Plasma Exchange n=10 Participants Participants randomized to plasma exchange
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg Day 11 · Only intact IgG	0 Participants	5 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg Day 11 · Mix of intact IgG and scIgG	0 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg Day 11 · Only scIgG	0 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg Day 11 · Mix of scIgG and F(ab')2	0 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg Day 11 · Only F(ab')2	0 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg Day 11 · No intact IgG, scIgG, or F(ab')2	0 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg Day 15 · Only intact IgG	0 Participants	1 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg Day 15 · Mix of intact IgG and scIgG	0 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg Day 15 · Only scIgG	0 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg Day 15 · Mix of scIgG and F(ab')2	0 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg Day 15 · Only F(ab')2	0 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg Day 15 · No intact IgG, scIgG, or F(ab')2	0 Participants	1 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg 2 hours · Only scIgG	0 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg 2 hours · Mix of scIgG and F(ab')2	2 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg 2 hours · Only F(ab')2	17 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg 6 hours · Only intact IgG	0 Participants	10 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg 6 hours · Only scIgG	0 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg 6 hours · Mix of scIgG and F(ab')2	0 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg 6 hours · Only F(ab')2	19 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg 48 hours · Only intact IgG	0 Participants	8 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg 72 hours · Mix of scIgG and F(ab')2	1 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg 72 hours · Only F(ab')2	16 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg 96 hours · Mix of scIgG and F(ab')2	0 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg Day 6 · Only F(ab')2	0 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg Day 8 · Only scIgG	0 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg Day 8 · No intact IgG, scIgG, or F(ab')2	0 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg 48 hours · Only scIgG	0 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg 48 hours · Mix of scIgG and F(ab')2	1 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg Baseline · Only scIgG	0 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg Baseline · Only intact IgG	19 Participants	10 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg Baseline · Mix of intact IgG and scIgG	0 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg Baseline · Mix of scIgG and F(ab')2	0 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg Baseline · Only F(ab')2	0 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg Baseline · No intact IgG, scIgG, or F(ab')2	0 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg 2 hours · Only intact IgG	0 Participants	10 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg 2 hours · Mix of intact IgG and scIgG	0 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg 2 hours · No intact IgG, scIgG, or F(ab')2	0 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg 6 hours · Mix of intact IgG and scIgG	0 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg 6 hours · No intact IgG, scIgG, or F(ab')2	0 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg 24 hours · Only intact IgG	0 Participants	9 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg 24 hours · Mix of intact IgG and scIgG	0 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg 24 hours · Only scIgG	0 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg 24 hours · Mix of scIgG and F(ab')2	0 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg 24 hours · Only F(ab')2	19 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg 24 hours · No intact IgG, scIgG, or F(ab')2	0 Participants	1 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg 48 hours · Mix of intact IgG and scIgG	0 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg 48 hours · Only F(ab')2	18 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg 48 hours · No intact IgG, scIgG, or F(ab')2	0 Participants	2 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg 72 hours · Only intact IgG	0 Participants	10 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg 72 hours · Mix of intact IgG and scIgG	2 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg 72 hours · Only scIgG	0 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg 72 hours · No intact IgG, scIgG, or F(ab')2	0 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg 96 hours · Only intact IgG	0 Participants	9 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg 96 hours · Mix of intact IgG and scIgG	0 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg 96 hours · Only scIgG	0 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg 96 hours · Only F(ab')2	0 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg 96 hours · No intact IgG, scIgG, or F(ab')2	0 Participants	1 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg Day 6 · Only intact IgG	0 Participants	10 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg Day 6 · Mix of intact IgG and scIgG	0 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg Day 6 · Only scIgG	0 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg Day 6 · Mix of scIgG and F(ab')2	0 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg Day 6 · No intact IgG, scIgG, or F(ab')2	0 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg Day 8 · Only intact IgG	0 Participants	8 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg Day 8 · Mix of intact IgG and scIgG	0 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg Day 8 · Mix of scIgG and F(ab')2	0 Participants	0 Participants
Number of Patients With Intact IgG, Single-cleaved IgG (scIgG), F(ab')2 Fragments Following Treatment Until Administration of IVIg Day 8 · Only F(ab')2	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Screening until Day 6

Population: Data was missing for a number of patients.

An MFI value above 6000 is indicative of complement fixation. Analysis of DSA functionality assessed as mean MFI levels was done before and after treatment.

Outcome measures

Measure	Imlifidase n=19 Participants Participants randomized to imlifidase	Plasma Exchange n=10 Participants Participants randomized to plasma exchange
DSA Functionality Determined by C1q Analysis Pre- and Post-treatment Pre-dose	19827 MFI counts Standard Deviation 11910	18848 MFI counts Standard Deviation 9958
DSA Functionality Determined by C1q Analysis Pre- and Post-treatment Day 2	319 MFI counts Standard Deviation 432	15576 MFI counts Standard Deviation 12008
DSA Functionality Determined by C1q Analysis Pre- and Post-treatment Day 6	5065 MFI counts Standard Deviation 9768	11926 MFI counts Standard Deviation 13076

SECONDARY outcome

Timeframe: Pre-dose, 30 min, 1 h, 2 h, 6 h, 24 h, 48 h, 72 h, 96 h, Day 6, Day 8, Day 1, and Day 15

Cmax = Maximum observed plasma concentration of imlifidase following dosing

Outcome measures

Measure	Imlifidase n=19 Participants Participants randomized to imlifidase	Plasma Exchange Participants randomized to plasma exchange
Pharmacokinetic (PK) Profile of Imlifidase: Cmax	4.3 µg/mL Geometric Coefficient of Variation 18	—

SECONDARY outcome

Timeframe: Pre-dose, 30 min, 1 h, 2 h, 6 h, 24 h, 48 h, 72 h, 96 h, Day 6, Day 8, Day 1, and Day 15

Tmax = Time point for maximum observed plasma concentration of imlifidase following dosing

Outcome measures

Measure	Imlifidase n=19 Participants Participants randomized to imlifidase	Plasma Exchange Participants randomized to plasma exchange
PK Profile of Imlifidase: Tmax	0.6 h Interval 0.4 to 2.3	—

SECONDARY outcome

Timeframe: Pre-dose, 30 min, 1 h, 2 h, 6 h, 24 h, 48 h, 72 h, 96 h, Day 6, Day 8, Day 1, and Day 15

Population: The data presents only patients who's time-concentration profile could be fitted to a 2-compartment model

t1/2 = terminal half-life of imlifidase (refers to the time required for plasma concentration of a drug to decrease by 50%) Different mathematical models are available to describe how drugs are adsorbed, distributed, metabolised, and eliminated from the body. The time-concentration curve of imlifidase could be fitted to the so called 2-compartment model. This model divide the body into a central and an peripheral compartment. The central compartment consist of the plasma and tissues where the distribution is fast and the peripheral consists of tissues where the distribution of the drug is slower. As a result the elimination of imlifidase consists of an initial phase with a short half life (alpha-t1/2) and an elimination phase with a longer half-life (beta-t1/2).

Outcome measures

Measure	Imlifidase n=19 Participants Participants randomized to imlifidase	Plasma Exchange Participants randomized to plasma exchange
PK Profile of Imlifidase: t1/2 Alpha t1/2 (initial phase)	2.7 h Interval 1.4 to 6.0	—
PK Profile of Imlifidase: t1/2 Beta t1/2 (elimination phase)	39.7 h Interval 23.5 to 128.0	—

SECONDARY outcome

Timeframe: Pre-dose, 30 min, 1 h, 2 h, 6 h, 24 h, 48 h, 72 h, 96 h, Day 6, Day 8, Day 1, and Day 15

Area under the imlifidase plasma concentration vs time curve (AUC)

Outcome measures

Measure	Imlifidase n=16 Participants Participants randomized to imlifidase	Plasma Exchange Participants randomized to plasma exchange
PK Profile of Imlifidase: AUC	124 h×µg/mL Geometric Coefficient of Variation 62	—

SECONDARY outcome

Timeframe: Pre-dose, 30 min, 1 h, 2 h, 6 h, 24 h, 48 h, 72 h, 96 h, Day 6, Day 8, Day 1, and Day 15

Clearance (CL) of imlifidase means the volume of blood cleared of imlifidase per unit of time.

Outcome measures

Measure	Imlifidase n=16 Participants Participants randomized to imlifidase	Plasma Exchange Participants randomized to plasma exchange
PK Profile of Imlifidase: CL	2.0 mL/h/kg Geometric Coefficient of Variation 62	—

SECONDARY outcome

Timeframe: Pre-dose, 30 min, 1 h, 2 h, 6 h, 24 h, 48 h, 72 h, 96 h, Day 6, Day 8, Day 1, and Day 15

Vss = volume of distribution associated with steady state VZ = volume of distribution associated with the elimination phase

Outcome measures

Measure	Imlifidase n=16 Participants Participants randomized to imlifidase	Plasma Exchange Participants randomized to plasma exchange
PK Profile of Imlifidase: Volume of Distribution (V) Vss	0.64 L/kg Geometric Coefficient of Variation 722	—
PK Profile of Imlifidase: Volume of Distribution (V) Vz	0.54 L/kg Geometric Coefficient of Variation 547	—

SECONDARY outcome

Timeframe: Screening until Day 180

Samples were collected and analysed for presence of anti-imlifidase IgG throughout the study.

Imlifidase is an IgG-degrading enzyme of Streptococcus pyogenes. Patients who have been exposed to Streptococcus prior to participating in this trial tested positive for ADA also before exposure to imlifidase.

Outcome measures

Measure	Imlifidase n=19 Participants Participants randomized to imlifidase	Plasma Exchange Participants randomized to plasma exchange
Concentration of Anti-drug Antibodies (ADAs) Day 64	122 mg/L Geometric Coefficient of Variation 496	—
Concentration of Anti-drug Antibodies (ADAs) Pre-dose	6.7 mg/L Geometric Coefficient of Variation 70	—
Concentration of Anti-drug Antibodies (ADAs) 24 hours	2.0 mg/L Geometric Coefficient of Variation 0	—
Concentration of Anti-drug Antibodies (ADAs) Day 8	15 mg/L Geometric Coefficient of Variation 66	—
Concentration of Anti-drug Antibodies (ADAs) Day 11	20 mg/L Geometric Coefficient of Variation 149	—
Concentration of Anti-drug Antibodies (ADAs) Day 15	49 mg/L Geometric Coefficient of Variation 275	—
Concentration of Anti-drug Antibodies (ADAs) Day 22	73 mg/L Geometric Coefficient of Variation 300	—
Concentration of Anti-drug Antibodies (ADAs) Day 29	87 mg/L Geometric Coefficient of Variation 398	—
Concentration of Anti-drug Antibodies (ADAs) Day 90	135 mg/L Geometric Coefficient of Variation 536	—
Concentration of Anti-drug Antibodies (ADAs) Day 180	100 mg/L Geometric Coefficient of Variation 725	—

Adverse Events

Imlifidase

Serious events: 3 serious events

Other events: 17 other events

Deaths: 1 deaths

Plasma Exchange

Serious events: 3 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Measure	Imlifidase n=19 participants at risk Participants randomized to imlifidase	Plasma Exchange n=10 participants at risk Participants randomized to plasma exchange
Blood and lymphatic system disorders Leukocytosis	0.00% 0/19 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Blood and lymphatic system disorders Nephrogenic anaemia	0.00% 0/19 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Gastrointestinal disorders Abdominal pain	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Musculoskeletal and connective tissue disorders Muscle haemorrhage	0.00% 0/19 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Renal and urinary disorders Acute kidney injury	10.5% 2/19 • Number of events 2 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.

Other adverse events

Measure	Imlifidase n=19 participants at risk Participants randomized to imlifidase	Plasma Exchange n=10 participants at risk Participants randomized to plasma exchange
Blood and lymphatic system disorders Anaemia	10.5% 2/19 • Number of events 2 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Blood and lymphatic system disorders Leukocytosis	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Blood and lymphatic system disorders Leukopenia	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Blood and lymphatic system disorders Lymphopenia	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Blood and lymphatic system disorders Thrombocytopenia	21.1% 4/19 • Number of events 5 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Blood and lymphatic system disorders Thrombotic microangiopathy	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Cardiac disorders Tachycardia	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Ear and labyrinth disorders Ear discomfort	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Ear and labyrinth disorders Tinnitus	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Eye disorders Visual impairment	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Gastrointestinal disorders Abdominal distension	0.00% 0/19 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Gastrointestinal disorders Abdominal hernia	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Gastrointestinal disorders Abdominal pain upper	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Gastrointestinal disorders Ascites	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Gastrointestinal disorders Constipation	10.5% 2/19 • Number of events 2 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Gastrointestinal disorders Diarrhoea	5.3% 1/19 • Number of events 2 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Gastrointestinal disorders Dyspepsia	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Gastrointestinal disorders Flatulence	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Gastrointestinal disorders Food poisoning	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Gastrointestinal disorders Mouth ulceration	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Gastrointestinal disorders Nausea	10.5% 2/19 • Number of events 3 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Gastrointestinal disorders Vomiting	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
General disorders Asthenia	0.00% 0/19 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
General disorders Catheter site haemorrhage	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
General disorders Catheter site pain	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
General disorders Chest pain	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
General disorders Fatigue	15.8% 3/19 • Number of events 3 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
General disorders Gait disturbance	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
General disorders Malaise	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
General disorders Non-cardiac chest pain	0.00% 0/19 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
General disorders Oedema peripheral	15.8% 3/19 • Number of events 3 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
General disorders Pyrexia	0.00% 0/19 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Hepatobiliary disorders Hepatocellular injury	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Immune system disorders Transplant rejection	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Infections and infestations Cytomegalovirus infection	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Infections and infestations Sinusitis	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Injury, poisoning and procedural complications Infusion related reaction	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Injury, poisoning and procedural complications Overdose	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Injury, poisoning and procedural complications Renal lymphocele	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Investigations Acid base balance abnormal	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Investigations Antibody test positive	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Investigations BK polyomavirus test positive	0.00% 0/19 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Investigations Blood creatinine increased	15.8% 3/19 • Number of events 3 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	10.0% 1/10 • Number of events 3 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Investigations Blood glucose fluctuation	0.00% 0/19 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Investigations Blood triglycerides increased	10.5% 2/19 • Number of events 2 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Investigations C-reactive protein increased	0.00% 0/19 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	20.0% 2/10 • Number of events 2 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Investigations Immunosuppressant drug level increased	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Metabolism and nutrition disorders Calcium deficiency	0.00% 0/19 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Metabolism and nutrition disorders Dehydration	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Metabolism and nutrition disorders Dyslipidaemia	0.00% 0/19 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Metabolism and nutrition disorders Folate deficiency	0.00% 0/19 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Metabolism and nutrition disorders Hypercholesterolaemia	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Metabolism and nutrition disorders Hyperglycaemia	21.1% 4/19 • Number of events 10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	20.0% 2/10 • Number of events 2 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Metabolism and nutrition disorders Hyperkalaemia	15.8% 3/19 • Number of events 3 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	40.0% 4/10 • Number of events 4 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Metabolism and nutrition disorders Hyperphosphataemia	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Metabolism and nutrition disorders Hypertriglyceridaemia	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Metabolism and nutrition disorders Hypokalaemia	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	20.0% 2/10 • Number of events 2 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Metabolism and nutrition disorders Hypomagnesaemia	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Metabolism and nutrition disorders Metabolic acidosis	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Musculoskeletal and connective tissue disorders Arthralgia	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/19 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Musculoskeletal and connective tissue disorders Muscle spasms	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Musculoskeletal and connective tissue disorders Myalgia	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Musculoskeletal and connective tissue disorders Pain in extremity	10.5% 2/19 • Number of events 2 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Nervous system disorders Dysgeusia	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Nervous system disorders Headache	10.5% 2/19 • Number of events 4 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Nervous system disorders Tremor	0.00% 0/19 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Psychiatric disorders Anxiety	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Psychiatric disorders Depressed mood	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Psychiatric disorders Feeling of despair	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Psychiatric disorders Panic attack	0.00% 0/19 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Psychiatric disorders Sleep disorder	0.00% 0/19 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Renal and urinary disorders Acute kidney injury	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Renal and urinary disorders Dysuria	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Renal and urinary disorders Incontinence	0.00% 0/19 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Renal and urinary disorders Proteinuria	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Respiratory, thoracic and mediastinal disorders Bronchospasm	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Respiratory, thoracic and mediastinal disorders Pulmonary congestion	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/19 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	10.0% 1/10 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Vascular disorders Hypertension	5.3% 1/19 • Number of events 1 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	0.00% 0/10 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.
Vascular disorders Hypotension	0.00% 0/19 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.	20.0% 2/10 • Number of events 2 • Adverse events (AEs) were collected for 6 months (i.e., from the timepoint the participant signed the informed consent form (ICF) until end of study, including the follow-up period). AEs occurring after the start of trial treatment and within the time of residual drug effect which is 28 days after start of trial treatment are classified as treatment emergent AEs (TEAEs). AEs were obtained if spontaneously reported, if reported in response to an open question from the study personnel or if revealed by observation. The reported data consists of TEAEs regardless of whether they are considered treatment-related or non-treatment-related. The reported data on mortality includes the 6 months follow-up period.

Additional Information

Vice President Research and Development

Hansa Biopharma AB

Phone: +4646165670

Email: info@hansabiopharma.com

Results disclosure agreements

• Principal investigator is a sponsor employee At the end of the study, one or more manuscripts for joint publication may be prepared in collaboration between the investigator(s) offered authorship and Hansa Biopharma. Any confidential information relating to imlifidase or the study, including any data and results from the study will be the exclusive property of Hansa Biopharma AB. The investigators and any other persons involved in the trial will protect the confidentiality of the proprietary information belonging to Hansa Biopharma AB.
• Publication restrictions are in place

Restriction type: OTHER