Efficacy, safety, and pharmacokinetics of natalizumab in Japanese multiple sclerosis patients

A double-blind, randomized controlled trial and open-label pharmacokinetic study

Takahiko Saida, Jun-Ichi Kira, Shuji Kishida, Takashi Yamamura, Yukiko Sudo, Kazutaka Ogiwara, J. T. Tibung, Nisha Lucas, Meena Subramanyam

Research output: Contribution to journalArticle

8 Citations (Scopus)

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 300 mg (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).

Original languageEnglish
Pages (from-to)25-31
Number of pages7
JournalMultiple Sclerosis and Related Disorders
Volume11
DOIs
Publication statusPublished - Jan 1 2017

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Multiple Sclerosis
Randomized Controlled Trials
Pharmacokinetics
Safety
Relapsing-Remitting Multiple Sclerosis
Placebos
Recurrence
Natalizumab
Gadolinium
Integrins
Monoclonal Antibodies
Brain

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

Cite this

Efficacy, safety, and pharmacokinetics of natalizumab in Japanese multiple sclerosis patients : A double-blind, randomized controlled trial and open-label pharmacokinetic study. / Saida, Takahiko; Kira, Jun-Ichi; Kishida, Shuji; Yamamura, Takashi; Sudo, Yukiko; Ogiwara, Kazutaka; Tibung, J. T.; Lucas, Nisha; Subramanyam, Meena.

In: Multiple Sclerosis and Related Disorders, Vol. 11, 01.01.2017, p. 25-31.

Research output: Contribution to journalArticle

Saida, Takahiko ; Kira, Jun-Ichi ; Kishida, Shuji ; Yamamura, Takashi ; Sudo, Yukiko ; Ogiwara, Kazutaka ; Tibung, J. T. ; Lucas, Nisha ; Subramanyam, Meena. / Efficacy, safety, and pharmacokinetics of natalizumab in Japanese multiple sclerosis patients : A double-blind, randomized controlled trial and open-label pharmacokinetic study. In: Multiple Sclerosis and Related Disorders. 2017 ; Vol. 11. pp. 25-31.
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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 300 mg (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).",
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T2 - A double-blind, randomized controlled trial and open-label pharmacokinetic study

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AU - Kira, Jun-Ichi

AU - Kishida, Shuji

AU - Yamamura, Takashi

AU - Sudo, Yukiko

AU - Ogiwara, Kazutaka

AU - Tibung, J. T.

AU - Lucas, Nisha

AU - Subramanyam, Meena

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N2 - 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 300 mg (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).

AB - 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 300 mg (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).

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