Assessment of Clemastine Fumarate as a Remyelinating Agent in Multiple Sclerosis

A Phase II Randomized, Double-Blind, Parallel-Group, Placebo Controlled Crossover Trial to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of Clemastine Fumarate as a Remyelinating Agent in Multiple Sclerosis

The main purpose of this study is to assess clemastine as a remyelinating agent in patients with relapsing forms of multiple sclerosis. The study will also evaluate the tolerability of clemastine, originally approved as first-generation antihistamine, in patients with multiple sclerosis. Study procedures will include assessments for evidence of remyelination in the anterior visual pathway and in the brain using electrophysiologic techniques and magnetic resonance imaging. The study will also assess the robustness and stability of this clinical effect in patients taking clemastine for up to 3 months. Patients in this study can remain on their standard disease modifying treatment during the course of the study. However, patients cannot participate in any other investigational new drug research study concurrently.

Inclusion Criteria:

• Relapsing remitting Multiple Sclerosis by 2010 Revised McDonald Criteria
• Age 18-60.
• Latency delay > 125 milliseconds on baseline full-field transient pattern reversal visual evoked potential (VEP) in at least one eye (electrophysiological evidence of demyelination)
• Retinal nerve fiber layer (RNFL) > 70 microns on Spectralis Domain Optical Coherence Topography (SD-OCT) in the same eye meeting criteria for latency delay (sufficient axons)
• No optic neuritis in prior 6 months
• Stable immunomodulatory therapy - no switch or planned switch in > 6 months and no change in doses in 30 days prior to screening
• Use of appropriate contraception during period of trial (females of child bearing potential)
• Understand and sign informed consent.
• Expanded disability status scale (EDSS) 0-6.0 (inclusive)

Exclusion Criteria:

• Major ophthalmologic disease / Concomitant ophthalmologic disorders (e.g. diabetes, macular degeneration, glaucoma, severe myopia , etc).
• Myopia > -7 Diopters (Severe myopia)
• History of significant cardiac conduction block
• History of cancer
• Known optic neuritis in involved eye > 5 years ago OR disease duration > 15 years
• Suicidal ideation or behaviour in 6 months prior to screening
• Pregnancy, breastfeeding, or planning to become pregnant.
• Involved with other study protocol simultaneously without prior approval. 9. Concomitant use of Dalfampridine (4AP or diamino4AP) or any other formulation of 4AP or diamino4AP.
• Concomitant use of any other putative remyelinating therapy as determined by investigator.
• Treatment with corticosteroids within 30 days prior to screening
• Prior treatment with total lymphoid irradiation, T cell or T cell receptor vaccination
• Prior treatment with alemtuzumab, mitoxantrone, or cyclophosphamide
• Serum creatinine > 1.5 mg/dL; aspartate aminotransferase (AST), alanine aminotransferase (ALT) or alkaline phosphatase > 2 times the upper limit of normal
• History of drug or alcohol abuse within the past year
• Untreated vitamin B12 deficiency (as determined by B12 serological assessments and metabolites including methylmalonic acid (MMA) and homocysteine) or untreated hypothyroidism
• Clinically significant cardiac, metabolic, hematologic, hepatic, immunologic, urologic, endocrinologic, neurologic, pulmonary, psychiatric, dermatologic, psychiatric allergic, renal or other major diseases that in the PI's judgment may affect interpretation of study results or patient safety.
• History of or presence of clinically significant medical illness or laboratory abnormality that, in the opinion of the investigator would preclude participation in the study