A Phase 1 Trial of Intrathecal Rituximab for Progressive Multiple Sclerosis Patients
Status:
Completed
Trial end date:
2017-08-01
Target enrollment:
Participant gender:
Summary
Multiple sclerosis (MS) is a chronic inflammatory disorder affecting the central nervous
system that is characterized pathologically by focal demyelinating lesions in the brain
parenchyma. Meningeal inflammation in MS was first noted in 2004. Ectopic lymphoid follicles
were described in the meninges of patients with secondary progressive MS (SPMS) and were
thought to correlate with cortical lesions and atrophy (a surrogate marker for disability).
Subsequently, inflammation in the meninges has been described in primary progressive MS
(PPMS) as well as early relapsing MS.
The ectopic lymphoid follicles are composed of B-cells, T follicular helper cells and
follicular dendritic cells. Rituximab is a monoclonal antibody against CD-20 (a B-cell
marker) that is FDA approved for the treatment of various lymphomas. Intrathecal (IT)
rituximab administration has been used in central nervous system (CNS) lymphoma to achieve
greater cerebrospinal fluid (CSF) concentrations of rituximab. In MS, IT administration of
rituximab could lead to higher CSF rituximab levels resulting in the disruption of meningeal
ectopic lymphoid follicles, ultimately reducing cortical lesions and possibly disease
progression.
The investigators hypothesize that IT rituximab therapy in patients with progressive forms of
MS could disrupt ectopic lymphoid follicles in the meninges and thus slow progression of the
disease, which is particularly important because there exist no FDA-approved therapies for
progressive MS. The investigators hypothesize that using magnetic resonance imaging (MRI) to
identify those with enhancing meningeal lesions will provide a biomarker to select patients
who might be most likely to respond to IT rituximab and to use these lesions to monitor
therapeutic response.
The primary aim of this study is to assess the safety of intrathecal administration of
rituximab in patients with progressive MS. The secondary aims are to evaluate if IT rituximab
leads to a decrease in the quantity of meningeal lesions on MRI or to changes in biomarkers
of inflammatory activity or neuronal injury in the CSF.