Abstract Details

Title Positive phase II double-blind randomized placebo-controlled crossover trial of clemastine fumarate for remyelination of chronic optic neuropathy in MS

Topic Multiple Sclerosis

Presentation(s) (-)

Poster/Presentation
Number 008

Background No reparative therapies exist for the treatment of MS. Clemastine was identified as a robust potential remyelinating agent using the in-vitro micropillar screen (BIMA) developed at UCSF. Following in-vivo validation, an FDA IND exemption was granted to investigate clemastine for the treatment of MS. Visual evoked potentials (VEPs) are capable of measuring conduction speed for electrical signals through the visual pathway and serve as a putative biomarker for remyelination.

Objective

Design/Methods We conducted a phase II randomized double-blind placebo-controlled crossover trial comparing twice daily oral clemastine to placebo in 50 patients with MS and chronic demyelinating optic neuropathy. The study period was 150 days. The pre-specified primary efficacy end point was change in latency delay on VEP. Trial outcomes were analyzed using mixed effects multivariable linear regression models.

Results Enrolled patient’s average age was 40.1 years, EDSS 2.1, and disease duration 5.1 years. Retention was 100% through the course of the study. There was a reduction of the primary efficacy endpoint of VEP latency delay of 1.9 ms/eye (95% CI [.66, 3.1]; p=.003) for the period on treatment. A strong trend for improvement of the principal secondary endpoint of low contrast visual acuity (LCVA) was also observed (p=.089). Clemastine treatment was associated with mild worsening of fatigue on the multidimensional assessment of fatigue (p=.017).

Conclusions In MS patients with chronic optic neuropathy, clemastine improved VEP latency delay and demonstrated a beneficial trend for the secondary endpoint of LCVA. This is the first RCT documenting efficacy for a candidate remyelinating agent in MS.

Authors/Disclosures
Ari Green, MD (UCSF)	Dr. Green has received personal compensation in the range of $50,000-$99,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pipeline Therapeutics. Dr. Green has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Bionure. Dr. Green has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for JAMA Neurology. The institution of Dr. Green has received research support from NINDS. The institution of Dr. Green has received research support from NMSS. The institution of Dr. Green has received research support from NIA. The institution of Dr. Green has received research support from Adelson Research Foundation. Dr. Green has received intellectual property interests from a discovery or technology relating to health care. Dr. Green has received personal compensation in the range of $500-$4,999 for serving as a Study Section with NINDS. Dr. Green has a non-compensated relationship as a Author with Viela Bio that is relevant to AAN interests or activities.
Jeffrey M. Gelfand, MD, MAS, FAAN (University of California, San Francisco)	Dr. Gelfand has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Arialys. Dr. Gelfand has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ventyx Bio. An immediate family member of Dr. Gelfand has received personal compensation in the range of $50,000-$99,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Headache: The Journal of Head and Face Pain. The institution of Dr. Gelfand has received research support from Genentech/Roche. The institution of Dr. Gelfand has received research support from Vigil Neurosciences. An immediate family member of Dr. Gelfand has received publishing royalties from a publication relating to health care. Dr. Gelfand has received publishing royalties from a publication relating to health care. Dr. Gelfand has received publishing royalties from a publication relating to health care. Dr. Gelfand has a non-compensated relationship as a Trial Steering Committee Chairperson and member with Roche / Genentech that is relevant to AAN interests or activities.
Bruce A. Cree, MD, PhD, MAS, FAAN (UCSF, Multiple Sclerosis Center)	The institution of Dr. Cree has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for EMD Serono. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for TG Therapeutics. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Autobahn. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avotres. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Horizon. Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Neuron23. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Boston Pharma. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Hexal/Sandoz. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kyverna. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Immunic AG. The institution of Dr. Cree has received research support from Genentech. The institution of Dr. Cree has received research support from Kyverna. Dr. Cree has received publishing royalties from a publication relating to health care.
Carolyn J. Bevan, MD (Jesse Brown VAMC)	Dr. Bevan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Bevan has received intellectual property interests from a discovery or technology relating to health care.
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Stephen L. Hauser, MD (UCSF Weill Institute for Neurosciences)	Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NGM Bio. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Moderna. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BD. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pheno Therapeutics. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Nurix Therapeutics. Dr. Hauser has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gilead. Dr. Hauser has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Accure. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alector. Dr. Hauser has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Annexon. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hinge Therapeutics. Dr. Hauser has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Neurona. Dr. Hauser has a non-compensated relationship as a Clinical Trial/Primary Investigator with Roche that is relevant to AAN interests or activities. Dr. Hauser has a non-compensated relationship as a Clinical Trial/Primary Investigator with Novartis that is relevant to AAN interests or activities.
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