Universität zu Köln

Limmroth, Volker, Barkhof, Frederik ORCID: 0000-0003-3543-3706, Desem, Nuket, Diamond, Mark P. and Tachas, George (2014). CD49d antisense drug ATL1102 reduces disease activity in patients with relapsing-remitting MS. Neurology, 83 (20). S. 1780 - 1789. PHILADELPHIA: LIPPINCOTT WILLIAMS & WILKINS. ISSN 1526-632X

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Abstract

Objective: This study evaluated the efficacy and safety of ATL1102, an antisense oligonucleotide that selectively targets the RNA for human CD49d, the a subunit of very late antigen 4, in patients with relapsing-remitting multiple sclerosis (RRMS). Methods: 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. Results: 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. Conclusions: In patients with RRMS, ATL1102 significantly reduced disease activity after 8 weeks of treatment and was generally well-tolerated. This trial provides evidence for the first time that antisense oligonucleotides may be used as a therapeutic approach in neuroimmunologic disorders. Classification: This study provides Class I evidence that for patients with RRMS, the antisense oligonucleotide ATL1102 reduces the number of new active head MRI lesions.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Limmroth, Volker UNSPECIFIED UNSPECIFIED UNSPECIFIED Barkhof, Frederik UNSPECIFIED orcid.org/0000-0003-3543-3706 UNSPECIFIED Desem, Nuket UNSPECIFIED UNSPECIFIED UNSPECIFIED Diamond, Mark P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Tachas, George UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-423429
DOI:	10.1212/WNL.0000000000000926
Journal or Publication Title:	Neurology
Volume:	83
Number:	20
Page Range:	S. 1780 - 1789
Date:	2014
Publisher:	LIPPINCOTT WILLIAMS & WILKINS
Place of Publication:	PHILADELPHIA
ISSN:	1526-632X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PLACEBO-CONTROLLED TRIAL; MULTIPLE-SCLEROSIS; INTERFERON-BETA; B-CELLS; METAANALYTIC APPROACH; INTEGRIN ANTIBODY; DOUBLE-BLIND; NATALIZUMAB; LYMPHOCYTES; EXPRESSION Multiple languages Clinical Neurology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/42342