Imlifidase treatment for acute inflammation in AQP4-IgG associated neuromyelitis optica spectrum disorder

Aquaporin-4 IgG seropositive neuromyelitis optica spectrum disorder (AQP4-IgG
positive NMOSD) is a rare demyelinating inflammatory disorder presenting with
episodes of severe inflammation in typically the optic nerve(s) and/or spinal
cord. The AQP4 antibodies are believed to be pathogenic and as such
contributing to the inflammation and resulting, often severe, neurological
deficits. Since old and new maintenance therapies reduce but not abrogate the
overall risk of attacks, persisting attacks remain the most important mediator
of persistent disability in NMOSD. In order to reduce neurological damage rapid
aggressive treatment of the acute attack of inflammation is indicated.
Momentarily standard care to reduce attack related damage includes intravenous
methylprednisolone (IVMP) for all patients. Sometimes, in severely affected
patients, based on individualized clinical decision making taking in into
account severity of disability, and trends towards recovery, this is followed
by a subsequent second course of IVMP and possibly additional treatment with 5
courses plasmapheresis over 2 weeks . The latter treatment is believed to
result in a faster recovery and less residual neurological disability by
depleting circulating pathogenic anti-AQP4 antibodies. We hypothesize that
anti-AQP4 IgG antibodies can be reduced in an early phase of acute attack
treatment using imlifidase.

To analyse in what proportion of NMOSD patients with an episode of acute
inflammation circulating pathogenic anti-AQP4 IgG antibodies are depleted below
detection limits, as measured with a state-of-the-arts cell-based assay, in the
timeframe within 6h after treatment with imlifidase

Open label, single arm, single center phase 2 study.

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 imlifidase. The concentrate will be added to
50 mL sodium chloride 9mg.mL (0.9%) solution for infusion and administered as
an infusion to 0.25mg/kg

The study investigates the biochemical effectiveness and safety of an add-on
experimental treatment to standard care. Standard care comprises a 5-day course
of 1000mg intravenous methylprednisolone daily. The intervention is the
addition of a single 15-minute intravenous infusion with imlifidase. The risk
of imlifidase treatment comprises infusion related reaction and infection.
Follow up assessment will be done whilst patients are admitted to the Neurology
ward, as per standard care, for the first 3 days after imlifidase infusion.
During these days there will be 9 blood sampling moments, via intravenous
access, follow up of adverse events, vital signs, neurological examination,
urine analysis and electrocardiogram.
Subsequently, there will be 7 follow-up visits for which patients, if
discharged, will be requested to visit the out-patient neurology department.
During these visits there will be blood sampling via vena puncture, which is a
low-risk procedure with possible minor risks of pain or local haematoma, and
urine analysis. There will also be an assessment of (serious) adverse events,
physical examination, recording of vital signs, neurological examination,
patient reported outcome measures (EQ-5D and patient determined disease steps).
These visits will replace the visits part of standard care, generally 2-4
visits in the first year after a severe relapse which would also include
neurological examination and blood sampling. Except from the burden of extra
site visits and minimal risk from blood sampling there will be no additional
burden for participants.
This study may be a first step towards a new, fast treatment modality for
patients suffering from NMOSD, which may prevent long-term disability.