devic disease neuromyelitis optica spectrum disorder
Conditions
Interventions
Imlifidase is provided as freeze-dried powder for concentrate for solution for
infusion, 11mg per vial. After reconstitution with sterile water for injection
the concentrate contains 10mg/mL imlifid
Sponsors
neurologie
Eligibility
Age
18 Years to 99 Years
Inclusion 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. NMOSD diagnosed according to the Wingerchuck criteria[6] with a positive anti-AQP4 IgG serum test using a cell-based assay at presentation or in medical history. 5. Onset of weakness or loss of visual acuity due to the exacerbation of NMOSD is not more than 14 days prior to administration of imlifidase. 6. Exacerbation of myelitis is associated with an increase in functional system motor score of at least 1 point, and requires at least bilateral assistance to walk; exacerbation of uni- or bilateral optic neuritis is associated with an increase in functional system visual score of at least 1 point, and results in a visual acuity of 20/60 to 20/99 (0.33-0.21) or worse. 7. Acute steroid treatment is indicated. 8. Incident cases or prevalent cases treated with maintenance/ prophylactic therapies including azathioprine, mycophenolate mofetil/mycophenol acid, and rituximab, or no maintenance treatment. 9. Negative serological screening test for hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus. 10. 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. 11. 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
Exclusion criteria: 1. Previous treatment with imlifidase 2. Subjects who are already on plasma exchange. 3. Intravenous immunoglobulin (IVIg) treatment 28 days prior to administration of imlifidase 4. Women of child-bearing potential unwilling or unable to use at least one highly effective contraceptive method from the screening visit until at least 180 days following imlifidase dosing. 5. Hypersensitivity to IVIg or to any of the excipients. 6. Signs or symptoms suggestive of Thrombotic Thrombocytopenic Purpura 7. Subject known to have a severe concurrent disease, e.g. malignancy, severe cardiovascular disease and severe chronic obstructive pulmonary disease. 8. 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. 9. Known mental incapacity or language barriers precluding adequate understanding of the Informed Consent information and the study activities. 10 Subjects with clinical signs of ongoing infectious diseases that requires treatment. 11. Subjects with active SARS-CoV-2 (COVID-19) infection as shown by PCR 12. Subjects should not have received other investigational drugs within 5 half-lives prior to imlifidase dosing.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - Circulating anti-AQP4-IgG levels at the predefined time points (0h, 0.5h, 1h, 2h, 4h, 6h, 8h, 1d, 2d, 3d, 7d, 14d, 21d, 28d, 64d, 180d) to day 180 as analysed with cell-based flowcytometry assay. | — |
Secondary
| Measure | Time frame |
|---|---|
| - Number of adverse events and serious adverse events within the timeframe to day 180. - Laboratory abnormalities within the timeframe to day 180. - Results of physical examination and vital signs - Samples for Anti-imlifidase IgG (anti-drug antibodies). Aliquoting of each sample and dedicate for PK, PD and ADA. - Levels of total IgG antibodies at predefined time points to day 180 -Total IgG (pharmacodynamics, PD) and imlifidase concentration (pharmacokinetics, PK) will be determined in serum by Hansa Biopharma, Sweden after inclusion of two patients and after inclusion of five patients. -Pharmacokinetics and pharmacodynamics of imlifidase at the predefined time-points 0h, 0.5h, 1h, 2h, 4h, 6h, 8h, 1d (24h), 2d (48h), 3d (72h), 7d (168h), 14 d Other study parameters Exploratory clinical endpoints - Mean change in EDSS and from baseline to time 7 days, 28 days, 64 days, 180 days - Mean change in functional system motor score or functional system visual score from baseline to time 7 days, 28 days, 64 days, 180 days - Mean change in EQ-5D (patient reported outcome measure, PROM, regarding quality of life) at day 7, day 14, day 28, day 64, day 180 - Requirement of additional plasmapheresis for the treatment of the acute relapse. Exploratory laboratory endpoints - Serum levels of neurofilament light chain (NfL) at baseline, day 1, day 7, day 28, day 64 measured using a Siemens assay - Serum levels of Glial fibrillary acidic protein (GFAP) at baseline, day 1, day 7, day 28, day 64 measured using a Single Molecule Array (SIMOA) assay | — |
Countries
Netherlands
Outcome results
None listed