A Phase 1 Trial of Intrathecal Rituximab for Progressive Multiple Sclerosis Patients

Part of paid clinical trials in Baltimore, Maryland.

Sponsor
Johns Hopkins University
Study ID
NCT02253264
Phase
PHASE1
Status
Completed

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

Study Details

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.

Key Dates

Start date
Nov 30, 2014
Status verified
Aug 2017
Primary completion
Aug 31, 2017
Completion
Aug 31, 2017

Study Design

Enrollment
8 participants (actual)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Intrathecal rituximab
    25 mg of rituximab will be administered intrathecally by direct infusion over 10 minutes at two time points, two weeks apart.

Primary Outcome Measure

Number of serious adverse events over the course of the study at least possibly related to intrathecal rituximab therapy, as determined by the principal investigator. [ Time Frame: 1 year ]

Locations (1)

FacilityCityStateZIPSite coordinators
The Johns Hopkins HospitalBaltimoreMaryland21287-

Find similar trials in Baltimore, MD

By condition
Multiple sclerosis
By specialty
NeurologyBrain disordersAutoimmune disease
By research site
The Johns Hopkins Hospital· Baltimore, MD

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