A Study of Imlifidase in Patients With Guillain-Barré Syndrome

An Open-label, Single Arm, Multi-centre, Phase II Study Investigating Safety, Tolerability, Efficacy, Pharmacodynamics and Pharmacokinetics of Imlifidase in Patients With Guillain-Barré Syndrome, in Comparison With Matched Control Patients

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03943589

Enrollment

Registered

2019-05-09

Start date

2019-11-12

Completion date

2024-02-27

Last updated

2025-04-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Guillain-Barré Syndrome (GBS)

Brief summary

The study participants are patients which have been diagnosed with Guillain-Barré Syndrome (GBS) and are planned to receive treatment with intravenous immunoglobulin (IVIg). IVIg is a standard of care treatment for GBS patients. The patients in this study will be treated with the study medicine imlifidase on day 1, and with IVIg on days 3-7. The purpose of this study is to investigate the safety and effectiveness of imlifidase in patients diagnosed with GBS.

Detailed description

This is an open-label, single arm, multi-centre, phase II study of imlifidase in combination with standard care IVIg in patients with GBS. The study will recruit approximately 30 patients who are eligible for IVIg treatment based on current practice (i.e. GBS disability score \>3 and within 10 days of onset of weakness). All patients will receive imlifidase (Day 1) prior to standard care IVIg. There is growing body of evidence suggesting that GBS is an antibody-mediated disorder. In addition to supportive care, IVIg and Plasma Exchange (PE) are the two main immunological treatment options aimed at attenuating the autoreactive humoral immune response. Imlifidase is an IgG degrading enzyme with strict specificity. The hypothesis is that reduction of pathological antibodies may result in aborted progression, quicker recovery and less severe disease.

Interventions

DRUGImlifidase

All subjects will receive imlifidase (Day 1) prior to standard care IVIg

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Intervention model description

Data from patients enrolled in this trial will, if feasible, be compared with an external control group consisting of patients from the IGOS database (International Guillain-Barré Syndrome Outcome Study, ClinicalTrials.gov Identifier: NCT01582763).

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

1. Signed Informed Consent obtained before any study-related procedures. 2. Willingness and ability to comply with the protocol. 3. Male or female aged ≥18 years at the time of screening. 4. GBS diagnosed according to National Institute of Neurological Disorders and Stroke (NINDS) diagnostic criteria (Asbury et al. 1990). 5. Onset of weakness due to GBS is not more than 10 days prior to screening. 6. Unable to walk unaided for \>10 meters (grade ≥ 3 on GBS DS). 7. IVIg treatment being considered. 8. Women of child-bearing potential willing or able to use at least one highly effective contraceptive method from the day of treatment until at least 6 months after the dose of imlifidase if not abstinent. In the context of this study, an effective method is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly. 9. Men willing to use double-barrier contraception from the day of treatment until at least 2 months after the dose of imlifidase if not abstinent.

Exclusion criteria

1. Previous treatment with imlifidase. 2. Previous IVIg treatment within 28 days prior to imlifidase treatment. 3. Subjects who are being considered for, or already on, PE. 4. Women of child-bearing potential willing or able to use at least one highly effective contraceptive method from the screening visit until at least 180 days following imlifidase dosing. 5. Breastfeeding or pregnancy 6. Clinical evidence of a polyneuropathy of another cause e.g. diabetes mellitus (except mild sensory), alcoholism, vitamin deficiency, or porphyria. 7. Known selective immunoglobulin A (IgA) deficiency. 8. Hypersensitivity to IVIg or to any of the excipients. 9. Immunosuppressive treatment (e.g. azathioprine, cyclosporine, mycophenolate mofetil, tacrolimus, sirolimus or \> 20 mg prednisolone daily) during the last month. 10. Subject known to have a severe concurrent disease, e.g. malignancy, severe cardiovascular disease and severe chronic obstructive pulmonary disease (COPD). 11. Any condition that in the opinion of the investigator could increase the subject's risk by participating in the study or confound the outcome of the study. 12. Known mental incapacity or language barriers precluding adequate understanding of the Informed Consent information and the study activities. 13. Subjects with clinical signs of ongoing infection. 14. Subjects should not have received other investigational drugs within 5 half-lives prior to imlifidase dosing. 15. Present or history of thrombotic thrombocytopenic purpura (TTP), or known familial history of TTP. 16. Positive PCR test for SARS-CoV-2 virus infection.

Design outcomes

Primary

Measure	Time frame	Description
Patient's Health State Over Time as Assessed by EQ VAS	Day 8, Day 15, Day 29, Day 57, Day 92, Day 180, and Day 360	Quality of Life will be assessed using the EurQol group's EurQol - 5 dimension (EQ-5D) Health questionnaire. The EQ-5D consists of 2 parts: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ VAS records the patient's self-rated health on a vertical scale, where score 100 is 'The best health you can imagine' and score 0 is the 'The worst health you can imagine'.
Proportion of Patients Who Are Able to Run Over Time (GBS DS≤1)	Baseline to Day 360	Efficacy is assessed as proportion of patients able to run (i.e. Guillain Barré Syndrome disability score \[GBS DS\] ≤1) over time
Mean MRC Sum Score Over Time	Baseline until Day 180	Efficacy is assessed as Medical Research Council (MRC) sum score over time. The MRC sum score is widely used to assess the motor impairment in subjects with peripheral neuropathies. It is a sum score of power in 6 muscle groups on each side (abduction of arm, flexion of forearm, extension of the wrist, hip flexion, and extension of knee and dorsal flexion of the foot). The sum of these scores ranges from 0 (total paralysis) to 60 (normal power). It provides valuable information about the muscle strength. Change in MRC sum score helps in identification of GBS patients with treatment related fluctuation or exacerbation. The individual MRC grades are defined as follows: 0=No visible contraction,1=Visible contraction without movement of the limb, 2=Movement of the limb but not against gravity, 3=Movement against gravity (almost full range), 4=Movement against gravity and resistance, 5=Normal
Change From Baseline in MRC Sum Score Over Time	Baseline until Day 180	Efficacy is assessed as change in Medical Research Council (MRC) sum score. The MRC sum score is widely used to assess the motor impairment in subjects with peripheral neuropathies. It is a sum score of power in 6 muscle groups on each side (abduction of arm, flexion of forearm, extension of the wrist, hip flexion, and extension of knee and dorsal flexion of the foot). The sum of these scores ranges from 0 (total paralysis) to 60 (normal power). It provides valuable information about the muscle strength. Change in MRC sum score helps in identification of GBS patients with treatment related fluctuation or exacerbation. The individual MRC grades are defined as follows: 0=No visible contraction,1=Visible contraction without movement of the limb, 2=Movement of the limb but not against gravity, 3=Movement against gravity (almost full range), 4=Movement against gravity and resistance, 5=Normal
Mean R-ODS Over Time	Baseline to Day 360	The patients have rated their ability to perform different common activities using the Rasch-built overall disability score (R-ODS) questionnaire. R-ODS is a linearly weighted disease specific scale, which captures activities and social participation limitation in patients with immune-mediated neuropathies, including GBS. The questionnaire comprises 24 items ranging from ability to read a book or newspaper (as the easiest item to accomplish) to ability to run (most difficult item to accomplish). The response options for each item are: 0=Not possible, 1=Possible with effort, 2=Easy to perform. The obtained raw summed score is subsequently translated to a centile metric ranging from 0 (most severe disability) to 100 (no disability at all).
Change From Baseline in R-ODS Over Time	Baseline to Day 360	The patients have rated their ability to perform different common activities using the Rasch-built overall disability score (R-ODS) questionnaire. R-ODS is a linearly weighted disease specific scale, which captures activities and social participation limitation in patients with immune-mediated neuropathies, including GBS. The questionnaire comprises 24 items ranging from ability to read a book or newspaper (as the easiest item to accomplish) to ability to run (most difficult item to accomplish). The response options for each item are: 0=Not possible, 1=Possible with effort, 2=Easy to perform. The obtained raw summed score is subsequently translated to a centile metric ranging from 0 (most severe disability) to 100 (no disability at all).
Days in Hospital	Baseline to Day 360	The number of days the patients were admitted to hospital
Time in an ICU	Baseline until Day 360	Efficacy is assessed as time in an intensive care unit (ICU)
Need for Mechanical Ventilation	Baseline until Day 180	—
Guillain Barré Syndrome Disability Score (GBS DS) - Time to Improve by at Least 1 Grade	Baseline to Day 360	Efficacy is assessed as proportion of subjects with improvement of one (1) or more grades in disability outcome on the 6-point GBS DS over time. The 6-point Guillain Barré Syndrome disability score (GBS DS) is a widely accepted and easily obtainable scoring system used to assess disability status of GBS subjects. The DS score is as follows: 0=Healthy, 1=Minor symptoms and capable of running (subjects must be asked to run), 2=Able to walk independently 10 meters or more but unable to run, 3=Able to walk more than 10 meters across an open space with help, 4=Bedridden or chair bound, 5=Needing mechanical ventilation, 6=Dead
Guillain Barré Syndrome Disability Score (GBS DS) - Time to Improve by at Least 2 Grades	Baseline to Day 360	Efficacy is assessed as proportion of subjects with improvement of one (1) or more grades in disability outcome on the 6-point GBS DS over time. The 6-point Guillain Barré Syndrome disability score (GBS DS) is a widely accepted and easily obtainable scoring system used to assess disability status of GBS subjects. The DS score is as follows: 0=Healthy, 1=Minor symptoms and capable of running (subjects must be asked to run), 2=Able to walk independently 10 meters or more but unable to run, 3=Able to walk more than 10 meters across an open space with help, 4=Bedridden or chair bound, 5=Needing mechanical ventilation, 6=Dead
Guillain Barré Syndrome Disability Score (GBS DS) - Ability to Walk Unaided	Baseline to Day 360	Efficacy is assessed as proportion of subjects able to walk unaided (i.e. GBS DS=2) over time

Secondary

Measure	Time frame	Description
PK Profile of Imlifidase: Tmax	Within 2 hours before imlifidase dose until Day 15	Tmax=Time point for maximum observed plasma concentration of imlifidase following dosing
PK Profile of Imlifidase: AUC	Within 2 hours before imlifidase dose until Day 15	AUC=Area under the imlifidase plasma concentration versus time curve
PK Profile of Imlifidase: t1/2	Within 2 hours before imlifidase dose until Day 15	t1/2=Terminal half-life of imlifidase
PK Profile of Imlifidase: CL	Within 2 hours before imlifidase dose until Day 15	CL=Clearance of imlifidase
PK Profile of Imlifidase: V	Within 2 hours before imlifidase dose until Day 15	V=Volume of distribution
Pharmacodynamics - IgG Level in Serum Over Time	Within 2 hours before imlifidase dose until Day 15	The pharmacodynamic (PD) effect of imlifidase is assessed as the elimination of IgG. IgG is cleaved by imlifidase in two steps, the first cut generates single-cleaved IgG (scIgG), and the second cut generates one F(ab')2 fragment and one Fc fragment. The IgG concentration measured in serum using the MSD technology is the sum of intact IgG and scIgG and a decrease in the measured IgG concentration therefore represents complete cleavage of the IgG molecule to Fc and F(ab')2 fragments. For the first 16 patients included in the trial a more frequent PD sampling schedule was conducted. After amending the protocol a less frequent PD sampling schedule was applied.
Immunogenicity - Anti-imlifidase Antibodies (ADA) Over Time	Within 2 hours before imlifidase dose until Day 180	Anti-imlifidase IgG antibodies (ADA) in serum.
PK Profile of Imlifidase: Cmax	Within 2 hours before imlifidase dose until Day 15	Cmax=Maximum observed plasma concentration of imlifidase following dosing

Countries

France, Netherlands, United Kingdom

Participant flow

Participants by arm

Arm	Count
Imlifidase One (1) dose of imlifidase, 0.25 mg/kg, will be administered IV over 30 minutes, Day 1. IVIg, 0.4 g/kg, will be administered for 5 consecutive Days, starting on Day 3 at least 48 h after imlifidase administration. Imlifidase: All subjects will receive imlifidase (Day 1) prior to standard care IVIg	30
Total	30

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Death	1
Overall Study	Diagnosed with encephalomyelitis	1

Baseline characteristics

Characteristic	Imlifidase
Age, Continuous	55.6 years STANDARD_DEVIATION 18.5
Body mass index (BMI)	26.8 kg/m^2 STANDARD_DEVIATION 4.6
Race/Ethnicity, Customized Asian	2 Participants
Race/Ethnicity, Customized Black or African American	1 Participants
Race/Ethnicity, Customized Other	3 Participants
Race/Ethnicity, Customized White	24 Participants
Region of Enrollment France	26 participants
Region of Enrollment Netherlands	1 participants
Region of Enrollment United Kingdom	3 participants
Sex: Female, Male Female	14 Participants
Sex: Female, Male Male	16 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	1 / 30
other Total, other adverse events	28 / 30
serious Total, serious adverse events	7 / 30

Outcome results

Primary

Change From Baseline in MRC Sum Score Over Time

Efficacy is assessed as change in Medical Research Council (MRC) sum score. The MRC sum score is widely used to assess the motor impairment in subjects with peripheral neuropathies. It is a sum score of power in 6 muscle groups on each side (abduction of arm, flexion of forearm, extension of the wrist, hip flexion, and extension of knee and dorsal flexion of the foot). The sum of these scores ranges from 0 (total paralysis) to 60 (normal power). It provides valuable information about the muscle strength. Change in MRC sum score helps in identification of GBS patients with treatment related fluctuation or exacerbation. The individual MRC grades are defined as follows: 0=No visible contraction,1=Visible contraction without movement of the limb, 2=Movement of the limb but not against gravity, 3=Movement against gravity (almost full range), 4=Movement against gravity and resistance, 5=Normal

Time frame: Baseline until Day 180

Population: The full analysis set (FAS) consists of data from all dosed patients having a confirmed GBS diagnosis, i.e., patients re-evaluated and having change in diagnosis (incorrectly diagnosed with GBS at trial entry) were excluded.~26 patients with data at Day 6 and Day 8, 25 patients with data at Day 15

Arm	Measure	Group	Value (MEAN)	Dispersion
Imlifidase	Change From Baseline in MRC Sum Score Over Time	Day 2	2.9 score on a scale	Standard Deviation 8.23
Imlifidase	Change From Baseline in MRC Sum Score Over Time	Day 4	8.4 score on a scale	Standard Deviation 9.19
Imlifidase	Change From Baseline in MRC Sum Score Over Time	Day 6	10.3 score on a scale	Standard Deviation 9.81
Imlifidase	Change From Baseline in MRC Sum Score Over Time	Day 8	10.7 score on a scale	Standard Deviation 10.21
Imlifidase	Change From Baseline in MRC Sum Score Over Time	Day 29	10.0 score on a scale	Standard Deviation 12.99
Imlifidase	Change From Baseline in MRC Sum Score Over Time	Day 57	9.9 score on a scale	Standard Deviation 14.59
Imlifidase	Change From Baseline in MRC Sum Score Over Time	Day 92	12.7 score on a scale	Standard Deviation 12.96
Imlifidase	Change From Baseline in MRC Sum Score Over Time	Day 180	15.0 score on a scale	Standard Deviation 10.62
Imlifidase	Change From Baseline in MRC Sum Score Over Time	Day 15	11.2 score on a scale	Standard Deviation 10.42

Primary

Change From Baseline in R-ODS Over Time

The patients have rated their ability to perform different common activities using the Rasch-built overall disability score (R-ODS) questionnaire. R-ODS is a linearly weighted disease specific scale, which captures activities and social participation limitation in patients with immune-mediated neuropathies, including GBS. The questionnaire comprises 24 items ranging from ability to read a book or newspaper (as the easiest item to accomplish) to ability to run (most difficult item to accomplish). The response options for each item are: 0=Not possible, 1=Possible with effort, 2=Easy to perform. The obtained raw summed score is subsequently translated to a centile metric ranging from 0 (most severe disability) to 100 (no disability at all).

Time frame: Baseline to Day 360

Population: The full analysis set (FAS) consists of data from all dosed patients having a confirmed GBS diagnosis, i.e., patients re-evaluated and having change in diagnosis (incorrectly diagnosed with GBS at trial entry) were excluded.~24 patients with data at Day 15, 26 patients with data at Day 8, Day 57, Day 92 and day 360.

Arm	Measure	Group	Value (MEAN)	Dispersion
Imlifidase	Change From Baseline in R-ODS Over Time	Day 8	17.2 score on a scale	Standard Deviation 22.3
Imlifidase	Change From Baseline in R-ODS Over Time	Day 15	20.8 score on a scale	Standard Deviation 21.4
Imlifidase	Change From Baseline in R-ODS Over Time	Day 29	28.8 score on a scale	Standard Deviation 25.3
Imlifidase	Change From Baseline in R-ODS Over Time	Day 57	34.5 score on a scale	Standard Deviation 26.5
Imlifidase	Change From Baseline in R-ODS Over Time	Day 92	40.8 score on a scale	Standard Deviation 24.6
Imlifidase	Change From Baseline in R-ODS Over Time	Day 180	46.3 score on a scale	Standard Deviation 22.7
Imlifidase	Change From Baseline in R-ODS Over Time	Day 360	50.5 score on a scale	Standard Deviation 19.3

Primary

Days in Hospital

The number of days the patients were admitted to hospital

Time frame: Baseline to Day 360

Population: Safety analysis set

Arm	Measure	Value (MEAN)	Dispersion
Imlifidase	Days in Hospital	32.5 days	Standard Deviation 43.5

Primary

Guillain Barré Syndrome Disability Score (GBS DS) - Ability to Walk Unaided

Efficacy is assessed as proportion of subjects able to walk unaided (i.e. GBS DS=2) over time

Time frame: Baseline to Day 360

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Imlifidase	Guillain Barré Syndrome Disability Score (GBS DS) - Ability to Walk Unaided	Day 7	10 Participants
Imlifidase	Guillain Barré Syndrome Disability Score (GBS DS) - Ability to Walk Unaided	Day 8	10 Participants
Imlifidase	Guillain Barré Syndrome Disability Score (GBS DS) - Ability to Walk Unaided	Day 15	13 Participants
Imlifidase	Guillain Barré Syndrome Disability Score (GBS DS) - Ability to Walk Unaided	Day 29	14 Participants
Imlifidase	Guillain Barré Syndrome Disability Score (GBS DS) - Ability to Walk Unaided	Day 57	18 Participants
Imlifidase	Guillain Barré Syndrome Disability Score (GBS DS) - Ability to Walk Unaided	Day 92	20 Participants
Imlifidase	Guillain Barré Syndrome Disability Score (GBS DS) - Ability to Walk Unaided	Day 180	23 Participants
Imlifidase	Guillain Barré Syndrome Disability Score (GBS DS) - Ability to Walk Unaided	Day 360	24 Participants
Imlifidase	Guillain Barré Syndrome Disability Score (GBS DS) - Ability to Walk Unaided	Baseline	0 Participants
Imlifidase	Guillain Barré Syndrome Disability Score (GBS DS) - Ability to Walk Unaided	Day 2	4 Participants
Imlifidase	Guillain Barré Syndrome Disability Score (GBS DS) - Ability to Walk Unaided	Day 3	5 Participants
Imlifidase	Guillain Barré Syndrome Disability Score (GBS DS) - Ability to Walk Unaided	Day 4	9 Participants
Imlifidase	Guillain Barré Syndrome Disability Score (GBS DS) - Ability to Walk Unaided	Day 5	9 Participants
Imlifidase	Guillain Barré Syndrome Disability Score (GBS DS) - Ability to Walk Unaided	Day 6	9 Participants

Primary

Guillain Barré Syndrome Disability Score (GBS DS) - Time to Improve by at Least 1 Grade

Efficacy is assessed as proportion of subjects with improvement of one (1) or more grades in disability outcome on the 6-point GBS DS over time. The 6-point Guillain Barré Syndrome disability score (GBS DS) is a widely accepted and easily obtainable scoring system used to assess disability status of GBS subjects. The DS score is as follows: 0=Healthy, 1=Minor symptoms and capable of running (subjects must be asked to run), 2=Able to walk independently 10 meters or more but unable to run, 3=Able to walk more than 10 meters across an open space with help, 4=Bedridden or chair bound, 5=Needing mechanical ventilation, 6=Dead

Time frame: Baseline to Day 360

Arm	Measure	Value (MEDIAN)
Imlifidase	Guillain Barré Syndrome Disability Score (GBS DS) - Time to Improve by at Least 1 Grade	6.0 days

Primary

Guillain Barré Syndrome Disability Score (GBS DS) - Time to Improve by at Least 2 Grades

Time frame: Baseline to Day 360

Arm	Measure	Value (MEDIAN)
Imlifidase	Guillain Barré Syndrome Disability Score (GBS DS) - Time to Improve by at Least 2 Grades	16.0 days

Primary

Mean MRC Sum Score Over Time

Efficacy is assessed as Medical Research Council (MRC) sum score over time. The MRC sum score is widely used to assess the motor impairment in subjects with peripheral neuropathies. It is a sum score of power in 6 muscle groups on each side (abduction of arm, flexion of forearm, extension of the wrist, hip flexion, and extension of knee and dorsal flexion of the foot). The sum of these scores ranges from 0 (total paralysis) to 60 (normal power). It provides valuable information about the muscle strength. Change in MRC sum score helps in identification of GBS patients with treatment related fluctuation or exacerbation. The individual MRC grades are defined as follows: 0=No visible contraction,1=Visible contraction without movement of the limb, 2=Movement of the limb but not against gravity, 3=Movement against gravity (almost full range), 4=Movement against gravity and resistance, 5=Normal

Time frame: Baseline until Day 180

Arm	Measure	Group	Value (MEAN)	Dispersion
Imlifidase	Mean MRC Sum Score Over Time	Baseline	39.1 score on a scale	Standard Deviation 13.88
Imlifidase	Mean MRC Sum Score Over Time	Day 2	42.0 score on a scale	Standard Deviation 14.66
Imlifidase	Mean MRC Sum Score Over Time	Day 4	47.5 score on a scale	Standard Deviation 14.58
Imlifidase	Mean MRC Sum Score Over Time	Day 6	49.7 score on a scale	Standard Deviation 13.7
Imlifidase	Mean MRC Sum Score Over Time	Day 8	50.0 score on a scale	Standard Deviation 13.8
Imlifidase	Mean MRC Sum Score Over Time	Day 15	51.8 score on a scale	Standard Deviation 12.09
Imlifidase	Mean MRC Sum Score Over Time	Day 29	49.1 score on a scale	Standard Deviation 17.41
Imlifidase	Mean MRC Sum Score Over Time	Day 57	49.0 score on a scale	Standard Deviation 18.39
Imlifidase	Mean MRC Sum Score Over Time	Day 92	51.8 score on a scale	Standard Deviation 16.22
Imlifidase	Mean MRC Sum Score Over Time	Day 180	54.1 score on a scale	Standard Deviation 12.4

Primary

Mean R-ODS Over Time

Time frame: Baseline to Day 360

Population: The full analysis set (FAS) consists of data from all dosed patients having a confirmed GBS diagnosis, i.e., patients re-evaluated and having change in diagnosis (incorrectly diagnosed with GBS at trial entry) were excluded.~24 patients with data at Day 15, 26 patients with data at Day 8, Day 57, Day 92 and day 360.

Arm	Measure	Group	Value (MEAN)	Dispersion
Imlifidase	Mean R-ODS Over Time	Baseline	23.7 score on a scale	Standard Deviation 15.26
Imlifidase	Mean R-ODS Over Time	Day 8	41.9 score on a scale	Standard Deviation 28.01
Imlifidase	Mean R-ODS Over Time	Day 15	46.2 score on a scale	Standard Deviation 26.87
Imlifidase	Mean R-ODS Over Time	Day 29	52.6 score on a scale	Standard Deviation 33.12
Imlifidase	Mean R-ODS Over Time	Day 360	73.8 score on a scale	Standard Deviation 24.36
Imlifidase	Mean R-ODS Over Time	Day 57	57.2 score on a scale	Standard Deviation 34.54
Imlifidase	Mean R-ODS Over Time	Day 92	63.5 score on a scale	Standard Deviation 32.5
Imlifidase	Mean R-ODS Over Time	Day 180	70.0 score on a scale	Standard Deviation 29.17

Primary

Need for Mechanical Ventilation

Time frame: Baseline until Day 180

Population: Safety analysis set

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Imlifidase	Need for Mechanical Ventilation	Screening	0 Participants
Imlifidase	Need for Mechanical Ventilation	Day 1 to Day 90	1 Participants
Imlifidase	Need for Mechanical Ventilation	Day 5 to Day 102	1 Participants
Imlifidase	Need for Mechanical Ventilation	Day 9 to Day 90 and Day 103 to Day 180	1 Participants

Primary

Patient's Health State Over Time as Assessed by EQ VAS

Quality of Life will be assessed using the EurQol group's EurQol - 5 dimension (EQ-5D) Health questionnaire. The EQ-5D consists of 2 parts: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ VAS records the patient's self-rated health on a vertical scale, where score 100 is 'The best health you can imagine' and score 0 is the 'The worst health you can imagine'.

Time frame: Day 8, Day 15, Day 29, Day 57, Day 92, Day 180, and Day 360

Population: Safety analysis set 27 patients with data at Day 92 and Day180, 26 patients with data at Day 8 and Day 360, 25 patients with data at Day 29 and Day 57, 24 patients with data at Day 15.

Arm	Measure	Group	Value (MEAN)	Dispersion
Imlifidase	Patient's Health State Over Time as Assessed by EQ VAS	Day 8	49.7 EQ-5D-5L VAS score	Standard Deviation 23.7
Imlifidase	Patient's Health State Over Time as Assessed by EQ VAS	Day 15	61.3 EQ-5D-5L VAS score	Standard Deviation 24.8
Imlifidase	Patient's Health State Over Time as Assessed by EQ VAS	Day 29	67.3 EQ-5D-5L VAS score	Standard Deviation 21
Imlifidase	Patient's Health State Over Time as Assessed by EQ VAS	Day 57	68.8 EQ-5D-5L VAS score	Standard Deviation 25.1
Imlifidase	Patient's Health State Over Time as Assessed by EQ VAS	Day 92	75.2 EQ-5D-5L VAS score	Standard Deviation 23.9
Imlifidase	Patient's Health State Over Time as Assessed by EQ VAS	Day 180	78.6 EQ-5D-5L VAS score	Standard Deviation 20.6
Imlifidase	Patient's Health State Over Time as Assessed by EQ VAS	Day 360	79.4 EQ-5D-5L VAS score	Standard Deviation 18.6

Primary

Proportion of Patients Who Are Able to Run Over Time (GBS DS≤1)

Efficacy is assessed as proportion of patients able to run (i.e. Guillain Barré Syndrome disability score \[GBS DS\] ≤1) over time

Time frame: Baseline to Day 360

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Imlifidase	Proportion of Patients Who Are Able to Run Over Time (GBS DS≤1)	Baseline	0 Participants
Imlifidase	Proportion of Patients Who Are Able to Run Over Time (GBS DS≤1)	Day 180	17 Participants
Imlifidase	Proportion of Patients Who Are Able to Run Over Time (GBS DS≤1)	Day 2	0 Participants
Imlifidase	Proportion of Patients Who Are Able to Run Over Time (GBS DS≤1)	Day 3	0 Participants
Imlifidase	Proportion of Patients Who Are Able to Run Over Time (GBS DS≤1)	Day 4	0 Participants
Imlifidase	Proportion of Patients Who Are Able to Run Over Time (GBS DS≤1)	Day 5	1 Participants
Imlifidase	Proportion of Patients Who Are Able to Run Over Time (GBS DS≤1)	Day 6	1 Participants
Imlifidase	Proportion of Patients Who Are Able to Run Over Time (GBS DS≤1)	Day 7	2 Participants
Imlifidase	Proportion of Patients Who Are Able to Run Over Time (GBS DS≤1)	Day 8	4 Participants
Imlifidase	Proportion of Patients Who Are Able to Run Over Time (GBS DS≤1)	Day 15	5 Participants
Imlifidase	Proportion of Patients Who Are Able to Run Over Time (GBS DS≤1)	Day 29	9 Participants
Imlifidase	Proportion of Patients Who Are Able to Run Over Time (GBS DS≤1)	Day 57	11 Participants
Imlifidase	Proportion of Patients Who Are Able to Run Over Time (GBS DS≤1)	Day 92	15 Participants
Imlifidase	Proportion of Patients Who Are Able to Run Over Time (GBS DS≤1)	Day 360	18 Participants

Primary

Time in an ICU

Efficacy is assessed as time in an intensive care unit (ICU)

Time frame: Baseline until Day 360

Population: Safety analysis set

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Imlifidase	Time in an ICU	Admitted 0 days	18 Participants
Imlifidase	Time in an ICU	Admitted 2-11 days	9 Participants
Imlifidase	Time in an ICU	Admitted 106-113 days	2 Participants
Imlifidase	Time in an ICU	Admitted 172 days	1 Participants

Secondary

Immunogenicity - Anti-imlifidase Antibodies (ADA) Over Time

Anti-imlifidase IgG antibodies (ADA) in serum.

Time frame: Within 2 hours before imlifidase dose until Day 180

Population: 28 patients have data at Day 29, Day 57, Day 92, and Day 180

Arm	Measure	Group	Value (MEAN)	Dispersion
Imlifidase	Immunogenicity - Anti-imlifidase Antibodies (ADA) Over Time	Day 1, pre-dose	11.1 mg/L	Standard Deviation 17.1
Imlifidase	Immunogenicity - Anti-imlifidase Antibodies (ADA) Over Time	Day 2, 24 hours after dose	4.0 mg/L	Standard Deviation 9.6
Imlifidase	Immunogenicity - Anti-imlifidase Antibodies (ADA) Over Time	Day 3, before IVIg administration	4.5 mg/L	Standard Deviation 12.2
Imlifidase	Immunogenicity - Anti-imlifidase Antibodies (ADA) Over Time	Day 8	474.5 mg/L	Standard Deviation 909
Imlifidase	Immunogenicity - Anti-imlifidase Antibodies (ADA) Over Time	Day 15	2811.9 mg/L	Standard Deviation 3772.6
Imlifidase	Immunogenicity - Anti-imlifidase Antibodies (ADA) Over Time	Day 29	2120.1 mg/L	Standard Deviation 2813.7
Imlifidase	Immunogenicity - Anti-imlifidase Antibodies (ADA) Over Time	Day 57	1060.3 mg/L	Standard Deviation 1086.5
Imlifidase	Immunogenicity - Anti-imlifidase Antibodies (ADA) Over Time	Day 92	722.1 mg/L	Standard Deviation 806.8
Imlifidase	Immunogenicity - Anti-imlifidase Antibodies (ADA) Over Time	Day 180	336.0 mg/L	Standard Deviation 318.9

Secondary

Pharmacodynamics - IgG Level in Serum Over Time

The pharmacodynamic (PD) effect of imlifidase is assessed as the elimination of IgG. IgG is cleaved by imlifidase in two steps, the first cut generates single-cleaved IgG (scIgG), and the second cut generates one F(ab')2 fragment and one Fc fragment. The IgG concentration measured in serum using the MSD technology is the sum of intact IgG and scIgG and a decrease in the measured IgG concentration therefore represents complete cleavage of the IgG molecule to Fc and F(ab')2 fragments. For the first 16 patients included in the trial a more frequent PD sampling schedule was conducted. After amending the protocol a less frequent PD sampling schedule was applied.