ATON: results from a Phase II randomized trial of the B-cell-targeting agent atacicept in patients with optic neuritis.

Abstract

The 36-week ATON study compared the efficacy and safety of atacicept with matching placebo in 34 patients with unilateral optic neuritis as a clinically isolated syndrome. Atacicept (150mg) was administered twice weekly for 4weeks (loading period), then once weekly for 32weeks. The ATON study was terminated prematurely by the sponsor when an independent Data and Safety Monitoring Board review observed increased multiple sclerosis (MS)-related disease activity in the atacicept arms of the concurrent ATAcicept in MS (ATAMS) study. Analysis of the prematurely terminated ATON study showed that the mean (standard deviation) change from baseline in retinal nerve fiber layer thickness at last observed value in the affected eye was -8.6 (10.1) μm in patients treated with atacicept (n=15) compared with -17.3 (15.2) μm in patients treated with placebo (n=16). In the atacicept treatment group, a higher proportion of patients converted to clinically definite MS during the double-blind period compared with placebo (35.3% [6/17] vs 17.6% [3/17]). Treatment-emergent adverse events were similar across both treatment groups in the double-blind period. A dichotomy emerged with more atacicept-treated patients converting to relapsing-remitting MS compared with placebo-treated patients, despite the same patients experiencing less axonal loss after an optic neuritis event.

• Authors: Robert C Sergott, Jeffrey L Bennett, Peter Rieckmann, Xavier Montalban, Daniel Mikol, Ulrich Freudensprung, Thomas Plitz, Johan van Beek, ATON Trial Group
• Journal: Journal of the neurological sciences (J Neurol Sci) Vol. 351 Issue 1-2 Pg. 174-178 (Apr 15 2015) ISSN: 1878-5883 [Electronic] Netherlands
• PMID: 25758472 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Recombinant Fusion Proteins
• TACI receptor-IgG Fc fragment fusion protein

Topics

• Adult
• B-Lymphocytes (drug effects)
• Double-Blind Method
• Female
• Humans
• Male
• Multiple Sclerosis, Relapsing-Remitting (chemically induced)
• Nerve Fibers (drug effects, ultrastructure)
• Optic Neuritis (drug therapy)
• Recombinant Fusion Proteins (administration & dosage, adverse effects, pharmacology)
• Retinal Neurons (drug effects, ultrastructure)
• Tomography, Optical Coherence
• Treatment Outcome