Abstract Details

Title CLOCK-MS: Evaluating the Mechanism of Action of Cladribine Tablets via CNS and Blood Biomarkers in MS

Topic Multiple Sclerosis

Presentation(s) S49 - Multiple Sclerosis: Basic Science (1:48 PM-2:00 PM)

Poster/Presentation
Number 005

Objective

To generate hypotheses regarding the mechanisms of action of cladribine by assessing blood and cerebrospinal fluid (CSF) levels of lymphocyte subsets and other immune cells, as well as soluble immunological and neuronal injury markers, in study participants with relapsing forms of multiple sclerosis (RMS), before and during treatment with cladribine tablets.

Background

Cladribine tablets have been approved in more than 60 countries for various indications related to the treatment of RMS, and are proposed to function as an immune reconstitution therapy with potential to cross the blood-brain barrier. However, questions remain regarding the mechanism of action in RMS.

Design/Methods Cladribine tablets: collaborative study to evaluate impact on central nervous system biomarkers in multiple sclerosis (CLOCK-MS) will be a 24-month, open-label, randomized, multicenter, collaborative Phase IV biomarker research study. Approximately 50 subjects age 18–65, diagnosed with relapsing-remitting MS or active secondary progressive MS, who had inadequate response to, or were unable to tolerate, an alternate drug indicated for the treatment of RMS, and who are willing and able to undergo lumbar punctures (LPs), will be eligible for enrollment and treatment with cladribine tablets 10mg (3.5mg/kg cumulative dose over 2 years) per US Prescribing Information.

Results The primary endpoint will be change in CSF levels of CD3+ T lymphocytes, CD19+ B lymphocytes, and neurofilament light chain from baseline to second LP. Secondary endpoints include: changes in CSF levels of other lymphocyte subtypes and immune cells; CSF and serum levels of cladribine; peripheral blood levels of lymphocyte subtypes, other immune cells, and soluble immunological and neuronal injury markers; clinical and MRI outcomes; and safety outcomes.

Conclusions The results of CLOCK-MS are expected to provide insight into the impact of cladribine tablets on pathological B and T cell subsets, and inflammatory and neurodegeneration biomarkers in blood and CSF.

Authors/Disclosures
Gregory F. Wu, MD, FAAN PRESENTER	Dr. Wu has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Progentec. Dr. Wu has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Wu has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Journal of Neuroimmunology. Dr. Wu has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Department of Justice.
	No disclosure on file
Brooke Hayward, SM, MBA (EMD Serono, Inc.)	Brooke Hayward, SM, MBA has received personal compensation for serving as an employee of EMD Serono, Inc., Rockland, MA USA, an affiliate of Merck KGaA, Darmstadt, Germany.
John Walsh	No disclosure on file
Daniel Jones, PhD (EMD Serono)	No disclosure on file
Anne H. Cross, MD, FAAN (Washington University School of Medicine)	Dr. Cross has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Cross has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech / F. Hoffman la Roche. Dr. Cross has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Cross has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for TG Therapeutics. Dr. Cross has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Myers Squibb . Dr. Cross has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Octave. Dr. Cross has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Dr. Cross has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Cross has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Cross has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Cross has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Bristol Myers Squibb. Dr. Cross has received personal compensation in the range of $5,000-$9,999 for serving as an officer or member of the Board of Directors for Consortium of MS Centers. Dr. Cross has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for AAN. The institution of Dr. Cross has received research support from Genentech. Dr. Cross has received intellectual property interests from a discovery or technology relating to health care.

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