Log In

Forgot Password?
Create New Account

Loading... please wait

Abstract Details

Lack of Rebound Disease Activity in Participants with Relapsing Multiple Sclerosis Following Placebo Run-out in the Tolebrutinib Phase 2b Trial
Multiple Sclerosis
P6 - Poster Session 6 (5:30 PM-6:30 PM)
3-006
Rebound disease activity has been reported after discontinuing some MS disease-modifying treatments. The 16-week, double-blind, crossover, Phase 2b trial of brain-penetrant tolebrutinib in participants with RMS showed dose-dependent reductions in new gadolinium-enhancing T1 and new/enlarging T2-lesions. The unique crossover design with 4-week placebo run-in/run-out periods minimizing placebo exposure enabled assessment of potential rebound disease after tolebrutinib discontinuation. 

To assess potential rebound disease recrudescence in participants with relapsing multiple sclerosis (MS) after tolebrutinib Phase 2b trial (NCT03889639) placebo run-out period.

130 participants were randomized (1:1:1:1) to tolebrutinib 5, 15, 30, or 60 mg/day. MRI scans were obtained at screening and every 4 weeks for 16 weeks. Cohort 1 (n=64) received tolebrutinib for 12 weeks followed by 4-week placebo run-out; Cohort 2 (n=66) received 4-week placebo run-in followed by 12 weeks of tolebrutinib.

There was one relapse during Cohort 1 placebo run-out (98.4% relapse-free) vs four relapses in Cohort 2 placebo run-in (93.9% relapse-free). After 12 weeks of tolebrutinib treatment (Cohort 1), 83.3% of participants had no new gadolinium-enhancing lesions; after 4-week placebo run-out, 85.2% had no new gadolinium-enhancing lesions. In Cohort 1, mean±SD gadolinium-enhancing lesion count after 12 weeks of tolebrutinib was 0.37±0.99 and 0.44±1.70 after 4-week placebo run-out. In Cohort 1 participants receiving tolebrutinib 60 mg/day, mean±SD gadolinium-enhancing lesion count was 0.20±0.56 after 12 weeks of tolebrutinib and 0.31±0.70 after 4-week placebo run-out. The mean±SD gadolinium-enhancing lesion count after 4-week placebo run-in (Cohort 2) was 1.03±2.50. At Week 12 in Cohort 1, mean number of new/enlarging T2-lesions was 0.58±1.27 vs 0.95±2.72 after 4-week placebo run-out; meanwhile it was 2.12±5.16 after 4-week placebo run-in (Cohort 2).

These preliminary findings suggest tolebrutinib discontinuation in participants with RMS does not induce rebound disease activity; longer observation periods are needed to validate this finding.
Authors/Disclosures
Timothy J. Turner
PRESENTER
Timothy J. Turner has received personal compensation for serving as an employee of Sanofi. Timothy J. Turner has stock in Sanofi. Timothy J. Turner has received intellectual property interests from a discovery or technology relating to health care.
Anthony Traboulsee, MD (University of British Columbia) Dr. Traboulsee has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Dr. Traboulsee has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Traboulsee has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Traboulsee has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for EMD Serono. The institution of Dr. Traboulsee has received research support from Roche. The institution of Dr. Traboulsee has received research support from Genzyme.
Robert J. Fox, MD, FAAN (Cleveland Clinic) Dr. Fox has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AB Science. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Janssen. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for BMS. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for EMD Serono. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. Dr. Fox has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Immunic. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Fox has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TG Therapeutics. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genzyme. Dr. Fox has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Siemens. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for INmune Bio. Dr. Fox has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lily. Dr. Fox has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Greenwich Biosciences. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Immunic. Dr. Fox 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. Fox has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen. Dr. Fox has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AB Science. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. The institution of Dr. Fox has received research support from National Institutes of Health. The institution of Dr. Fox has received research support from National MS Society. Dr. Fox has received publishing royalties from a publication relating to health care.
Douglas L. Arnold, MD, FAAN (Montreal Neurological Institute, McGill Univ) Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for BMS. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Frequency Therapeutics. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck. Dr. Arnold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Arnold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Shionogi. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Xfacto communications. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Find therapeutics. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GSK. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Idorsia. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kiniksa. Dr. Arnold has stock in NeuroRx.
Sana Syed, MD (Sanofi Genzyme) Dr. Syed has received personal compensation for serving as an employee of Sanofi US.
Atuyota L. Orogun, MBBS (Sanofi) Dr. Orogun has nothing to disclose.
Deborah Dukovic No disclosure on file
Daniel Reich, MD, PhD (National Institutes of Health, Neuroimmunology Branch, NINDS) Dr. Reich has received research support from NIH. The institution of Dr. Reich has received research support from Adelson Medical Research Foundation. The institution of Dr. Reich has received research support from Sanofi-Genzyme. The institution of Dr. Reich has received research support from Abata Therapeutics. The institution of Dr. Reich has received research support from National Multiple Sclerosis Society. Dr. Reich has received personal compensation in the range of $500-$4,999 for serving as a CME Faculty with PeerView. Dr. Reich has received personal compensation in the range of $500-$4,999 for serving as a CME Faculty with AcademicCME. Dr. Reich has received personal compensation in the range of $500-$4,999 for serving as a CME Faculty with Integrity. Dr. Reich has a non-compensated relationship as a Advisor with Sanofi-Genzyme that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Board of Directors with ACTRIMS that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Abata Therapeutics that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with American Brain Foundation that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with University of Basel RC2NB that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Multiple Sclerosis Society of Canada that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Tuscan Doctorate in Neuroscience that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Editorial Board with Multiple Sclerosis Journal that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Biohaven that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Sana that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Merck KGaA EMD Serono that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Bristol-Meyers Squibb that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with ChemoCentryx that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Collaborator, Advisor with Hyperfine that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Collaborator with Imaginab that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Advisor with Perceptive that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Collaborator with Annexon that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Collaborator, Advisor with Philips that is relevant to AAN interests or activities. Dr. Reich has a non-compensated relationship as a Collaborator with Siemens that is relevant to AAN interests or activities.
Jiwon Oh, MD, FAAN (St Michael's Hospital) Dr. Oh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. The institution of Dr. Oh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen-Idec. Dr. Oh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. Dr. Oh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for EMD-Serono. Dr. Oh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Oh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Oh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Oh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Horizon Therapeutics. Dr. Oh has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Oh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen-Idec. Dr. Oh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi-Genzyme. The institution of Dr. Oh has received research support from Biogen-Idec. The institution of Dr. Oh has received research support from Roche.