This study evaluated the efficacy and safety of ATL1102, an antisense oligonucleotide that selectively targets the RNA for human CD49d, the α subunit of very late antigen 4, in patients with relapsing-remitting multiple sclerosis (RRMS).
In a multicenter, double-blind, placebo-controlled randomized phase II trial, 77 patients with RRMS were treated with 200 mg of ATL1102 subcutaneously injected 3 times in the first week and twice weekly for 7 weeks or placebo and monitored for a further 8 weeks. MRI scans were taken at baseline and weeks 4, 8, 12, and 16. The primary endpoint was the cumulative number of new active lesions (either new gadolinium-enhancing T1 lesions or nonenhancing new or enlarging T2 lesions) at weeks 4, 8, and 12.
A total of 72 patients completed the study and 74 intention-to-treat patients were assessed. ATL1102 significantly reduced the cumulative number of new active lesions by 54.4% compared to placebo (mean 3.0 [SD 6.12] vs 6.2 [9.89], p = 0.01). The cumulative number of new gadolinium-enhancing T1 lesions was reduced by 67.9% compared to placebo ( p = 0.002). Treatment-emergent adverse events included mild to moderate injection site erythema and decrease in platelet counts that returned to within the normal range after dosing.
Scientific consultant to Bayer-Schering, Sanofi- Aventis, Synthon, Novartis, Biogen-Idec, Merck-Serono, Synthon, GE Medical systems, Roche, Janssen, TEVA, Genzyme
Editorial board member for Brain, Eur Radiol, Multiple Sclerosis Journal, Neuroradiology, Radiology, Neurology
Consultant for Sanofi-Aventis, Synthon, Janssen, Novartis, Biogen-Idec, GE medical systems, Roche
Serono Symposia speaker , 2010 and 2011 Novartis symposium speaker 2009, 2010 and 2011 BioClinica symposium speaker 2010 Bayer-Schering symposium speaker 2010 Medscape CME speaker 2011 and 2012
Dutch foundation for MS Research - centre grant 2010-2014
Coinvestigators are listed on the Neurology® Web site at Neurology.org.
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. The Article Processing Charge was paid by Antisense Therapeutics Ltd.
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