Format

Send to

Choose Destination
Mult Scler Relat Disord. 2017 Jan;11:25-31. doi: 10.1016/j.msard.2016.11.002. Epub 2016 Nov 11.

Efficacy, safety, and pharmacokinetics of natalizumab in Japanese multiple sclerosis patients: A double-blind, randomized controlled trial and open-label pharmacokinetic study.

Author information

1
Kansai Multiple Sclerosis Center and Kyoto Min-iren Central Hospital, Kyoto, Japan. Electronic address: saida_takahiko@maia.eonet.ne.jp.
2
Department of Neurology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
3
Hakusuikai Hatsuishi Hospital, Chiba, Japan.
4
National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan.
5
Biogen Japan, Tokyo, Japan.
6
Biogen, Cambridge, MA, USA.

Abstract

BACKGROUND:

Natalizumab, an anti-α4 integrin monoclonal antibody, has demonstrated efficacy in phase 2 and 3 studies of predominantly Caucasian patients with relapsing-remitting multiple sclerosis (RRMS).

OBJECTIVE:

To evaluate the efficacy, safety, pharmacokinetics (PK), and pharmacodynamics (PD) of natalizumab in Japanese RRMS patients.

METHODS:

This multicenter, phase 2 study included an open-label PK/PD study in 12 patients (part A) and a double-blind, placebo-controlled, randomized (computer-generated sequence) study in 94 patients (part B). For part B, patients received intravenous natalizumab 300mg (n=47) or placebo (n=47) every 4 weeks. The primary efficacy endpoint was the rate of development of new active lesions (gadolinium-enhancing or new/enlarging T2 lesions) over 24 weeks. Clinical relapses and safety were also assessed.

RESULTS:

New active lesions developed at a significantly lower mean rate in natalizumab-treated patients (0.06 lesions/24 weeks) than in placebo-treated patients (0.35 lesions/24 weeks) (p<0.001). The annualized relapse rate was 0.53 for natalizumab and 1.73 for placebo (p<0.001). Twice as many natalizumab-treated patients (79%) as placebo-treated patients (38%) were relapse-free (p<0.001). The safety, PK, and PD profiles of natalizumab in this study were consistent with data in Caucasian RRMS patients.

CONCLUSIONS:

In Japanese RRMS patients, natalizumab treatment every 4 weeks for 24 weeks was well tolerated and reduced the development of new brain lesions and relapses (Funded by Biogen; ClinicalTrials.gov identifier: NCT01440101).

KEYWORDS:

Japanese; Multiple sclerosis; Natalizumab; Pharmacokinetics; Randomized clinical trial

PMID:
28104251
DOI:
10.1016/j.msard.2016.11.002
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center