A Study of Imlifidase in Patients With Guillain-Barré Syndrome

NCT03943589 | Completed Phase 2 Results DMC

• 1 other identifier: 15-HMedIdeS-09
• Study Type: interventional
• Target: 30
• Locations: 3 countries
• Sites: 11

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.

Conditions

Guillain-Barré Syndrome (GBS)

Outcome Measures

Primary Outcomes (12)

• 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

  Baseline to Day 360

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

  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

  Baseline to Day 360

• 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

  Baseline to Day 360

• 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

  Baseline to Day 360

• 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

  Baseline until Day 180

• 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

  Baseline until Day 180

• Mean 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).

  Baseline to Day 360

• 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).

  Baseline to Day 360

• Days in Hospital

  The number of days the patients were admitted to hospital

  Baseline to Day 360

• Time in an ICU

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

  Baseline until Day 360

• Need for Mechanical Ventilation

  Baseline until Day 180

• 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'.

  Day 8, Day 15, Day 29, Day 57, Day 92, Day 180, and Day 360

Secondary Outcomes (8)

• PK Profile of Imlifidase: Cmax

  Within 2 hours before imlifidase dose until Day 15

• PK Profile of Imlifidase: Tmax

  Within 2 hours before imlifidase dose until Day 15

• PK Profile of Imlifidase: AUC

  Within 2 hours before imlifidase dose until Day 15

• PK Profile of Imlifidase: t1/2

  Within 2 hours before imlifidase dose until Day 15

• PK Profile of Imlifidase: CL

  Within 2 hours before imlifidase dose until Day 15

Study Arms (1)

Imlifidase

EXPERIMENTAL

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.

Drug: Imlifidase

Interventions

Imlifidase DRUG

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

Also known as: Hansa Medical-Immunoglobulin G degrading enzyme of Streptococcus pyogenes (HMED-IdeS), IdeS, IgG endopeptidase

Imlifidase

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed Informed Consent obtained before any study-related procedures.
• Willingness and ability to comply with the protocol.
• Male or female aged ≥18 years at the time of screening.
• GBS diagnosed according to National Institute of Neurological Disorders and Stroke (NINDS) diagnostic criteria (Asbury et al. 1990).
• Onset of weakness due to GBS is not more than 10 days prior to screening.
• Unable to walk unaided for \>10 meters (grade ≥ 3 on GBS DS).
• IVIg treatment being considered.
• 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.
• 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.

You may not qualify if:

• Previous treatment with imlifidase.
• Previous IVIg treatment within 28 days prior to imlifidase treatment.
• Subjects who are being considered for, or already on, PE.
• 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.
• Breastfeeding or pregnancy
• Clinical evidence of a polyneuropathy of another cause e.g. diabetes mellitus (except mild sensory), alcoholism, vitamin deficiency, or porphyria.
• Known selective immunoglobulin A (IgA) deficiency.
• Hypersensitivity to IVIg or to any of the excipients.
• Immunosuppressive treatment (e.g. azathioprine, cyclosporine, mycophenolate mofetil, tacrolimus, sirolimus or \> 20 mg prednisolone daily) during the last month.
• Subject known to have a severe concurrent disease, e.g. malignancy, severe cardiovascular disease and severe chronic obstructive pulmonary disease (COPD).
• 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.
• Known mental incapacity or language barriers precluding adequate understanding of the Informed Consent information and the study activities.
• Subjects with clinical signs of ongoing infection.
• Subjects should not have received other investigational drugs within 5 half-lives prior to imlifidase dosing.
• Present or history of thrombotic thrombocytopenic purpura (TTP), or known familial history of TTP.

Sponsors & Collaborators

• Hansa Biopharma AB: lead

Study Sites (11)

CHU Le Kremlin-Bicêtre. Service Neurologie

Le Kremlin-Bicêtre, Paris, 94270, France

Location

CHU Bordeaux - Hôpital Pellegrin Tripode

Bordeaux, 33076, France

Location

CHU de Limoges - Hôpital Dupuytren

Limoges, 87000, France

Location

Hôpital de la Timone - Centre de référence des maladies neuromusculaires et de la SLA

Marseille, 13385, France

Location

CHU de Montpellier, Hôpital Gui de Chauliac

Montpellier, 34295, France

Location

Centre Hospitalier Universitaire de Nantes

Nantes, 44093, France

Location

Service de neurologie, Hôpitaux Universitaires de Strasbourg

Strasbourg, 67 098, France

Location

Amsterdam UMC

Amsterdam, Netherlands

Location

Erasmus Medical Centre

Rotterdam, 3015 GD, Netherlands

Location

Queen Elizabeth University Hospital Glasgow

Glasgow, United Kingdom

Location

Oxford University Hospital

Oxford, United Kingdom

Location

MeSH Terms

Conditions

Guillain-Barre Syndrome

Interventions

Mac-1-like protein, Streptococcus

Condition Hierarchy (Ancestors)

Polyradiculoneuropathy; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Vice President Research and Development
• Organization: Hansa Biopharma AB

info@hansabiopharma.com

+4646165670

Study Officials

• Clinical Operations

  Hansa Biopharma AB

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: April 30, 2019
• First Posted: May 9, 2019
• Study Start: November 12, 2019
• Primary Completion: February 27, 2024
• Study Completion: February 27, 2024
• Last Updated: April 9, 2025
• Results First Posted: April 9, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

NL (2); FR (7); GB (2)