A Study of Imlifidase in Patients With Guillain-Barré Syndrome

Phase 2

Completed

• Conditions: Guillain-Barré Syndrome (GBS)
• Interventions: Drug: Imlifidase

• Registration Number: NCT03943589
• Lead Sponsor: Hansa Biopharma AB

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.

Study Timeline

• Study First Submitted: 2019-04-30
• Study First Submitted QC: 2019-05-08
• Study First Posted: 2019-05-09
• Study Start: 2019-11-12
• Primary Completion: 2024-02-27
• Study Completion: 2024-02-27
• Results First Submitted: 2025-02-25
• Status Verified: 2025-03
• Results First Submitted QC: 2025-03-21
• Last Update Submitted: 2025-03-21
• Results First Posted: 2025-04-09
• Last Update Posted: 2025-04-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Imlifidase	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.

Primary Outcome Measures

Name	Time	Method
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
Need for Mechanical Ventilation	Baseline until Day 180
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'.
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
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
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).
Time in an ICU	Baseline until Day 360	Efficacy is assessed as time in an intensive care unit (ICU)
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
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
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
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

Secondary Outcome Measures

Name	Time	Method
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
PK Profile of Imlifidase: Cmax	Within 2 hours before imlifidase dose until Day 15	Cmax=Maximum observed plasma concentration of imlifidase following dosing
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.
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
Immunogenicity - Anti-imlifidase Antibodies (ADA) Over Time	Within 2 hours before imlifidase dose until Day 180	Anti-imlifidase IgG antibodies (ADA) in serum.

Trial Locations

Locations (11)

Erasmus Medical Centre; 🇳🇱 Rotterdam, Netherlands

CHU Le Kremlin-Bicêtre. Service Neurologie; 🇫🇷 Le Kremlin-Bicêtre, Paris, France

CHU Bordeaux - Hôpital Pellegrin Tripode; 🇫🇷 Bordeaux, France

CHU de Limoges - Hôpital Dupuytren; 🇫🇷 Limoges, France

Hôpital de la Timone - Centre de référence des maladies neuromusculaires et de la SLA; 🇫🇷 Marseille, France

CHU de Montpellier, Hôpital Gui de Chauliac; 🇫🇷 Montpellier, France

Centre Hospitalier Universitaire de Nantes; 🇫🇷 Nantes, France

Service de neurologie, Hôpitaux Universitaires de Strasbourg; 🇫🇷 Strasbourg, France

Amsterdam UMC; 🇳🇱 Amsterdam, Netherlands

Queen Elizabeth University Hospital Glasgow; 🇬🇧 Glasgow, United Kingdom

Oxford University Hospital; 🇬🇧 Oxford, United Kingdom