Clinical trial NCT03943589: A Study of Imlifidase in Patients With Guillain-Barré Syndrome
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Guillain-Barré Syndrome (GBS)
Lead sponsor: Hansa Biopharma AB
Sponsor class: INDUSTRY
First posted: 2019-05-09
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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).
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Guillain Barré Syndrome Disability Score (GBS DS) - Time to Improve by at Least 1 Grade
timeFrame: Baseline to Day 360
measure: Guillain Barré Syndrome Disability Score (GBS DS) - Time to Improve by at Least 2 Grades
timeFrame: Baseline to Day 360
measure: Guillain Barré Syndrome Disability Score (GBS DS) - Ability to Walk Unaided
timeFrame: Baseline to Day 360
measure: Proportion of Patients Who Are Able to Run Over Time (GBS DS≤1)
timeFrame: Baseline to Day 360
measure: Mean MRC Sum Score Over Time
timeFrame: Baseline until Day 180
measure: Change From Baseline in MRC Sum Score Over Time
timeFrame: Baseline until Day 180
measure: Mean R-ODS Over Time
timeFrame: Baseline to Day 360
measure: Change From Baseline in R-ODS Over Time
timeFrame: Baseline to Day 360
measure: Days in Hospital
timeFrame: Baseline to Day 360
measure: Time in an ICU
timeFrame: Baseline until Day 360
measure: Need for Mechanical Ventilation
timeFrame: Baseline until Day 180
measure: Patient's Health State Over Time as Assessed by EQ VAS
timeFrame: Day 8, Day 15, Day 29, Day 57, Day 92, Day 180, and Day 360
Secondary outcomes:
measure: PK Profile of Imlifidase: Cmax
timeFrame: Within 2 hours before imlifidase dose until Day 15
measure: PK Profile of Imlifidase: Tmax
timeFrame: Within 2 hours before imlifidase dose until Day 15
measure: PK Profile of Imlifidase: AUC
timeFrame: Within 2 hours before imlifidase dose until Day 15
measure: PK Profile of Imlifidase: t1/2
timeFrame: Within 2 hours before imlifidase dose until Day 15
measure: PK Profile of Imlifidase: CL
timeFrame: Within 2 hours before imlifidase dose until Day 15
measure: PK Profile of Imlifidase: V
timeFrame: Within 2 hours before imlifidase dose until Day 15
measure: Pharmacodynamics - IgG Level in Serum Over Time
timeFrame: Within 2 hours before imlifidase dose until Day 15
measure: Immunogenicity - Anti-imlifidase Antibodies (ADA) Over Time
timeFrame: Within 2 hours before imlifidase dose until Day 180
Other outcomes:
Locations:
city: Le Kremlin-Bicêtre
country: France
facility: CHU Le Kremlin-Bicêtre. Service Neurologie
state: Paris
city: Bordeaux
country: France
facility: CHU Bordeaux - Hôpital Pellegrin Tripode
city: Limoges
country: France
facility: CHU de Limoges - Hôpital Dupuytren
city: Marseille
country: France
facility: Hôpital de la Timone - Centre de référence des maladies neuromusculaires et de la SLA
city: Montpellier
country: France
facility: CHU de Montpellier, Hôpital Gui de Chauliac
city: Nantes
country: France
facility: Centre Hospitalier Universitaire de Nantes
city: Strasbourg
country: France
facility: Service de neurologie, Hôpitaux Universitaires de Strasbourg
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Centre
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth University Hospital Glasgow
city: Oxford
country: United Kingdom
facility: Oxford University Hospital
Study officials:
affiliation: Hansa Biopharma AB
name: Clinical Operations
role: STUDY_CHAIR
References: