C1-esterase Inhibitor (Cinryze) for Acute Treatment of Neuromyelitis Optica Exacerbation
Condition: Neuromyelitis Optica
MeSH terms: Neuromyelitis Optica
Study type: Interventional
Phase: Phase 1

Summary: 
      The overall objective is to evaluate the tolerability/safety and preliminary efficacy of
      CINRYZE® (C1 esterase inhibitor [human]) as add-on therapy for treatment of acute optic
      neuritis and/or transverse myelitis in NMO and NMOSD.

      Primary Objective: To evaluate the safety and tolerability of 3-5 doses of 1000 - 2000 Units
      intravenous CINRYZE in NMO/NMOSD patients during an acute exacerbation.

      Secondary Objectives:

        -  To determine the frequency of adverse events with CINRYZE in this patient population.

        -  To determine the effect of CINRYZE on NMO clinical scores (Expanded Disability Status
           Scale and Low Contrast Visual Acuity).

        -  To compare the change in MRI lesion size and extent following a course of CINRYZE.
    

Detailed description: 
      The rationale for using C1-esterase inhibitor (CINRYZE) in NMO is based on pathology showing
      a role for complement in active NMO lesions. NMO is not unique in involving complement, which
      may have a pathogenic role in other demyelinating diseases including multiple sclerosis.
      However, NMO is characterized by its complement involvement depositing in a rim or rosette
      pattern in all/most active lesions. In vitro, complement mediates damage initiated by
      anti-AQP4 antibody binding to astrocytes. The effector of antibody triggered cell damage is
      the complement cascade and blocking the complement cascade with C1-inhibitor prevents damage
      ex vivo. Based on mounting evidence, the consensus in the field is that prevention of the
      complement cascade in the CNS would ameliorate the damage caused in NMO inflammatory attacks.
      In contrast to a prevention trial, this study would provide for complement inhibition only
      during an active NMO attack. This approach is designed to administer the inhibitory drug when
      complement damage is at its peak which minimizes adverse effects from prolonged complement
      inhibition.

      Patients with NMO do not lack natural C1-esterase inhibitor, but artificially tipping the
      balance to suppress the complement pathways using purified human C1-esterase inhibitor in
      patients with hyperactive complement activation has been shown to be beneficial in myocardial
      infarction and sepsis. Similarly, the rationale for adding human C1-esterase inhibitor to the
      treatment for NMO acute exacerbations is to tip the balance toward complement suppression in
      an effort to reduce complement-mediated neurologic damage.

      This is a phase 1b open-label, interventional proof-of-concept study in which all subjects
      will receive 3 daily infusions of 2000 Units of intravenous CINRYZE at the onset of an NMO
      exacerbation, plus an additional 2 infusions of 1000 Units of intravenous CINRYZE during a
      second treatment phase with plasma exchange, if necessary.
    

Intervention name(s): C1-esterase inhibitor (Cinryze)
Intervention type(s): Drug
Other intervention name(s): Cinryze
Intervention MeSH terms: Complement C1s; Complement C1 Inhibitor Protein; Complement C1 Inactivator Proteins
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Neuromyelitis optica; Devic's disease; NMO; Devic