E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Guillain-Barré Syndrome (GBS) |
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E.1.1.1 | Medical condition in easily understood language |
Guillain-Barré Syndrome (GBS) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 26.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10018766 |
E.1.2 | Term | Guillain Barre syndrome |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Assess safety and tolerability of imlifidase in combination with standard IVIg treatment in GBS subjects |
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E.2.2 | Secondary objectives of the trial |
• Evaluate pharmacokinetics of imlifidase • Evaluate pharmacodynamics profile of imlifidase • Evaluate immunogenicity of imlifidase • Evaluate efficacy of imlifidase in subjects with GBS • Evaluate quality of life after imlifidase treatment in subjects with GBS • Evaluate healthcare resource utilization after imlifidase treatment in subjects with GBS • Evaluate the contribution of a dose of imlifidase on outcomes with respect to severity of symptoms and recovery time through a comparison with an externally matched cohort of GBS subjects • Evaluate the effect of imlifidase on exploratory biomarkers |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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.
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E.4 | Principal 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 childbearing potential who are not willing to use contraception 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 IgA deficiency 8. Hypersensitivity to IVIg or to any of the excipients. 9. Immunosuppressive treatment (e.g. azathioprine, cyclosporine, mycofenolatemofetil, 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 who 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.
A subject will be withdrawn from the study if more than 12 days elapse between the onset of weakness and planned imlifidase administration, thus preventing that the administration of IVIg after imlifidase administration would be later than 14 days after onset of weakness.
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety as measured by type, frequency and intensity of Adverse Event (AE) / Serious Adverse Event (SAE) and change from baseline in parameters of clinical laboratory tests, vital signs and Electrocardiograms (ECG). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Efficacy as assessed by: • Proportion of subjects with improvement of one or more grades in disability outcome (on the 6-point GBS disability score [DS]) over time. • Proportion of subjects with improvement of two or more grades in disability outcome (on the 6-point GBS DS) over time • Proportion of subjects with improvement of three or more grades in disability outcome (on the 6-point GBS DS) over time • Change in GBS DS over time • Proportion of subjects able to walk unaided (GBS DS ≤ 2) over time • Time to improvement by at least one, two and three grade(s) on the GBS DS • Time to walk independently (GBS DS ≤ 2). • Time to run (GBS DS ≤ 1) • Proportion of subjects that reach GBS DS ≤ 1 by week 26 • Proportion of subjects with an increase from baseline in R-ODS score by at least 6 points on the centile metric score over time. • Proportion of subjects with all R-ODS items above 0 at week 26 • Proportion of subjects requiring mechanical ventilation support (GBS DS 5). • Days on mechanical ventilation • Days in hospital and in an ICU • Changes in MRC sum score over time • Pharmacokinetics (PK) parameters Cmax, area under the curve (AUC), tmax, t½, V, Clearance (CL), of imlifidase • Pharmacodynamics (PD) effect by means of time course of IgG following administration of imlifidase |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
United Kingdom |
France |
Netherlands |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 6 |