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Abstract Details

A Phase 1, Multiple-dose Study of Elezanumab (ABT-555) in Patients with Relapsing Forms of Multiple Sclerosis
Multiple Sclerosis
S56 - MS Trials and Treatment (1:00 PM-1:11 PM)
001
Elezanumab is a fully humanized monoclonal antibody directed against repulsive guidance molecule A (RGMa). Studies in patients with multiple sclerosis (MS) demonstrate RGMa upregulation, which inhibits axonal growth and myelination, oligodendroglial regeneration and functional recovery after trauma or inflammation. Elezanumab treatment promoted axon regeneration, neuroprotection, remyelination, and immune modulation in several MS-relevant preclinical models. Elezanumab was previously well-tolerated as a single dose to healthy volunteers.
The current study evaluated multiple doses of elezanumab to determine its safety and tolerability in patients with relapsing forms of MS.

In this phase 1, double-blind, placebo-controlled, randomized, escalating multiple-dose 29-week study, patients were randomized into 3 treatment groups (150 mg, 600 mg, and 1800 mg elezanumab) and 1 placebo group. Of the 20 patients enrolled, 18 had relapsing-remitting MS and 2 had secondary progressive MS. Elezanumab doses were given intravenously every 4 weeks for a total of 4 doses, with a loading dose of double the maintenance dose given on Day 1. Assessments included adverse events (AEs), cerebral spinal fluid (CSF) and plasma biomarker analysis, and Expanded Disability Status Score (EDSS). Subsequently, magnetic resonance imaging and serum pharmacokinetics data will be reported.

The most common AE was headache (25% of all patients). Free soluble RGMa decreased with increasing levels of elezanumab in CSF, while total RGMa (both free and antibody-bound) increased linearly with CSF elezanumab exposure. Interleukin-10 also increased in the CSF following elezanumab administration compared with placebo. Through the end of the follow-up period, the majority of patients receiving elezanumab did not experience a clinically significant worsening or improvement in EDSS scores.

Elezanumab was well-tolerated and did not consistently result in symptom worsening in patients who received multiple doses of up to 1800 mg. Additional long-term studies are required to elucidate elezanumab efficacy in a more robust patient population.

Authors/Disclosures
Adam Ziemann, MD, PhD (Eli Lilly)
PRESENTER
Dr. Ziemann has received personal compensation for serving as an employee of AbbVie. Dr. Ziemann has received stock or an ownership interest from AbbVie.
Matthew Rosebraugh, PhD (AbbVie) Dr. Rosebraugh has received personal compensation for serving as an employee of AbbVie Inc. Dr. Rosebraugh has stock in AbbVie Inc..
No disclosure on file
Bruce A. Cree, MD, PhD, MAS, FAAN (UCSF, Multiple Sclerosis Center) The institution of Dr. Cree has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for EMD Serono. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for TG Therapeutics. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Autobahn. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avotres. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Horizon. Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Neuron23. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Boston Pharma. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Hexal/Sandoz. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kyverna. Dr. Cree has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Immunic AG. The institution of Dr. Cree has received research support from Genentech. The institution of Dr. Cree has received research support from Kyverna. Dr. Cree has received publishing royalties from a publication relating to health care.