Ublituximab for Acute Neuromyelitis Optica (NMO) Relapses
Condition: Neuromyelitis Optica; Neuromyelitis Optica Spectrum Disorder
MeSH terms: Neuromyelitis Optica; Optic Neuritis
Study type: Interventional
Phase: Phase 1

Summary: 
      Ublituximab (also known as LFB-R603) is a monoclonal antibody that specifically binds to the
      trans-membrane antigen CD20. The binding induces immune response that causes lysis of B
      cells.

      The rationale for using ublituximab in neuromyelitis optica (NMO) and neuromyelitis optica
      spectrum disorder (NMOSD) is based on the known roles of B cells, antibody production and
      plasma cells in the pathophysiology of NMO. NMO is characterized by the presence of an
      anti-Aquaporin-4 (AQP4) antibody, which can only be produced by differentiation of B cells to
      plasma cells. Because these anti-AQP4 antibodies may be pathogenic, B cells recognizing AQP4
      may be directly involved in the disease process as well. B cells also play a role as potent
      antigen presenting cells in NMO. The strongest evidence of the importance of B cells in NMO
      comes from studies of B cell depletion, most commonly with anti-CD20 monoclonal antibody,
      rituximab (Rituxan®).

      Rituximab has been shown in five retrospective and two prospective studies to be effective in
      reducing NMO relapses up to 90% and achieving remission in up to 80% of patients solely by
      its action on CD20+ B cells, despite no change in plasma cell population and anti-AQP4
      antibody titers. These human trials strongly suggest a critical role for B cells in the
      pathophysiology of human disease. While typically used in the prevention of disease, B-cell
      depletion may be beneficial in the treatment of an acute relapse as well. Emerging evidence
      indicates that peripheral B cells are activated during a relapse and plasmablast production
      of anti-AQP4 antibodies spikes. B cells are also found within acute lesions of the spinal
      cord and optic nerve suggesting roles both in the blood and in the central nervous system
      during a relapse.
    

Detailed description: 
      The overall objective is to assess the safety of ublituximab as add-on therapy to steroids
      for treatment of acute optic neuritis and/or transverse myelitis in NMO and NMOSD.

      Primary Objective To assess safety of acute B cell depletion in NMO subjects with acute
      relapse of optic neuritis or transverse myelitis who are treated with ublituximab +
      glucocorticoids beginning on dose administration and ending with recovery of B cells.

      Secondary Objectives

        -  To determine the B cell depletion pharmacokinetics of ublituximab in the NMO patients
           population with monthly B cell counts for up to 9 months.

        -  To determine the frequency of adverse events with ublituximab in this patient
           population.

      Trial Design Given the severity and the consequences of relapse in NMO, placebo treatment
      without steroid treatment is unethical and use of an active treatment is considered
      mandatory. The potential of currently utilized drugs and techniques to reduce the
      inflammation in NMO has been established primarily through expert consensus and small open
      label and retrospective studies.

      This is a Phase 1 open-label, standard-of-care, single treatment arm, unblinded, single
      center interventional trial in NMO/NMOSD patients in which experimental subjects will receive
      one (1) infusion of 450 mg of intravenous ublituximab at the onset of an NMO exacerbation in
      addition to standard of care treatment with daily intravenous glucocorticoid at 1000 mg for
      five days.
    

Intervention name(s): Ublituximab
Intervention type(s): Drug
Intervention description(s): Monoclonal antibody that specifically binds to the trans-membrane antigen CD20, which induces immune response that causes lysis of B cells.
Other intervention name(s): LFB-R603
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Transverse myelitis, optic neuritis, neuromyelitis optica