The first trial of CIM331, a humanized antihuman interleukin-31 receptor A antibody, in healthy volunteers and patients with atopic dermatitis to evaluate safety, tolerability and pharmacokinetics of a single dose in a randomized, double-blind, placebo-controlled study

O. Nemoto, M. Furue, H. Nakagawa, M. Shiramoto, R. Hanada, S. Matsuki, S. Imayama, M. Kato, I. Hasebe, K. Taira, M. Yamamoto, R. Mihara, K. Kabashima, T. Ruzicka, Jon Hanifin, Y. Kumagai

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

Summary: Background: The cytokine interleukin-31 (IL-31) is considered to be responsible for the development of pruritus in humans. At present, no available evidence has been provided on the safety and efficacy of blocking the IL-31 signal in humans for the amelioration of pruritus in atopic dermatitis (AD). CIM331 is a humanized antihuman IL-31 receptor A (IL-31RA) monoclonal antibody, which binds to IL-31RA to inhibit subsequent IL-31 signalling. Objectives: To assess the tolerability, safety, pharmacokinetics and preliminary efficacy of CIM331 in healthy Japanese and white volunteers, and Japanese patients with AD. Methods: In this randomized, double-blind, placebo-controlled phase I/Ib study, CIM331 was administered in a single subcutaneous dose. The primary outcomes were safety and tolerability; the exploratory analysis was efficacy. Results: No deaths, serious adverse events (AEs) or discontinuations due to AEs were reported in any part of the study. No dose-dependent increase in the incidence of AEs occurred in any part of the study. In healthy volunteers, all AEs occurred once in the placebo groups, and increased creatine phosphokinase was more common in the CIM331 groups. In patients with AD, CIM331 reduced pruritus visual analogue scale score to about -50% at week 4 with CIM331 compared with -20% with placebo. CIM331 increased sleep efficiency and decreased the use of hydrocortisone butyrate. Conclusions: A single subcutaneous administration of CIM331 was well tolerated in healthy volunteers and patients with AD. It decreased pruritus, sleep disturbance and topical use of hydrocortisone.

Original languageEnglish (US)
JournalBritish Journal of Dermatology
DOIs
StateAccepted/In press - 2015

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Interleukin Receptors
Atopic Dermatitis
Pruritus
Interleukins
Healthy Volunteers
Pharmacokinetics
Placebos
Safety
Antibodies
Sleep
Creatine Kinase
Visual Analog Scale
Hydrocortisone
Volunteers
Monoclonal Antibodies
Cytokines
Incidence

ASJC Scopus subject areas

  • Dermatology

Cite this

The first trial of CIM331, a humanized antihuman interleukin-31 receptor A antibody, in healthy volunteers and patients with atopic dermatitis to evaluate safety, tolerability and pharmacokinetics of a single dose in a randomized, double-blind, placebo-controlled study. / Nemoto, O.; Furue, M.; Nakagawa, H.; Shiramoto, M.; Hanada, R.; Matsuki, S.; Imayama, S.; Kato, M.; Hasebe, I.; Taira, K.; Yamamoto, M.; Mihara, R.; Kabashima, K.; Ruzicka, T.; Hanifin, Jon; Kumagai, Y.

In: British Journal of Dermatology, 2015.

Research output: Contribution to journalArticle

Nemoto, O. ; Furue, M. ; Nakagawa, H. ; Shiramoto, M. ; Hanada, R. ; Matsuki, S. ; Imayama, S. ; Kato, M. ; Hasebe, I. ; Taira, K. ; Yamamoto, M. ; Mihara, R. ; Kabashima, K. ; Ruzicka, T. ; Hanifin, Jon ; Kumagai, Y. / The first trial of CIM331, a humanized antihuman interleukin-31 receptor A antibody, in healthy volunteers and patients with atopic dermatitis to evaluate safety, tolerability and pharmacokinetics of a single dose in a randomized, double-blind, placebo-controlled study. In: British Journal of Dermatology. 2015.
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abstract = "Summary: Background: The cytokine interleukin-31 (IL-31) is considered to be responsible for the development of pruritus in humans. At present, no available evidence has been provided on the safety and efficacy of blocking the IL-31 signal in humans for the amelioration of pruritus in atopic dermatitis (AD). CIM331 is a humanized antihuman IL-31 receptor A (IL-31RA) monoclonal antibody, which binds to IL-31RA to inhibit subsequent IL-31 signalling. Objectives: To assess the tolerability, safety, pharmacokinetics and preliminary efficacy of CIM331 in healthy Japanese and white volunteers, and Japanese patients with AD. Methods: In this randomized, double-blind, placebo-controlled phase I/Ib study, CIM331 was administered in a single subcutaneous dose. The primary outcomes were safety and tolerability; the exploratory analysis was efficacy. Results: No deaths, serious adverse events (AEs) or discontinuations due to AEs were reported in any part of the study. No dose-dependent increase in the incidence of AEs occurred in any part of the study. In healthy volunteers, all AEs occurred once in the placebo groups, and increased creatine phosphokinase was more common in the CIM331 groups. In patients with AD, CIM331 reduced pruritus visual analogue scale score to about -50{\%} at week 4 with CIM331 compared with -20{\%} with placebo. CIM331 increased sleep efficiency and decreased the use of hydrocortisone butyrate. Conclusions: A single subcutaneous administration of CIM331 was well tolerated in healthy volunteers and patients with AD. It decreased pruritus, sleep disturbance and topical use of hydrocortisone.",
author = "O. Nemoto and M. Furue and H. Nakagawa and M. Shiramoto and R. Hanada and S. Matsuki and S. Imayama and M. Kato and I. Hasebe and K. Taira and M. Yamamoto and R. Mihara and K. Kabashima and T. Ruzicka and Jon Hanifin and Y. Kumagai",
year = "2015",
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TY - JOUR

T1 - The first trial of CIM331, a humanized antihuman interleukin-31 receptor A antibody, in healthy volunteers and patients with atopic dermatitis to evaluate safety, tolerability and pharmacokinetics of a single dose in a randomized, double-blind, placebo-controlled study

AU - Nemoto, O.

AU - Furue, M.

AU - Nakagawa, H.

AU - Shiramoto, M.

AU - Hanada, R.

AU - Matsuki, S.

AU - Imayama, S.

AU - Kato, M.

AU - Hasebe, I.

AU - Taira, K.

AU - Yamamoto, M.

AU - Mihara, R.

AU - Kabashima, K.

AU - Ruzicka, T.

AU - Hanifin, Jon

AU - Kumagai, Y.

PY - 2015

Y1 - 2015

N2 - Summary: Background: The cytokine interleukin-31 (IL-31) is considered to be responsible for the development of pruritus in humans. At present, no available evidence has been provided on the safety and efficacy of blocking the IL-31 signal in humans for the amelioration of pruritus in atopic dermatitis (AD). CIM331 is a humanized antihuman IL-31 receptor A (IL-31RA) monoclonal antibody, which binds to IL-31RA to inhibit subsequent IL-31 signalling. Objectives: To assess the tolerability, safety, pharmacokinetics and preliminary efficacy of CIM331 in healthy Japanese and white volunteers, and Japanese patients with AD. Methods: In this randomized, double-blind, placebo-controlled phase I/Ib study, CIM331 was administered in a single subcutaneous dose. The primary outcomes were safety and tolerability; the exploratory analysis was efficacy. Results: No deaths, serious adverse events (AEs) or discontinuations due to AEs were reported in any part of the study. No dose-dependent increase in the incidence of AEs occurred in any part of the study. In healthy volunteers, all AEs occurred once in the placebo groups, and increased creatine phosphokinase was more common in the CIM331 groups. In patients with AD, CIM331 reduced pruritus visual analogue scale score to about -50% at week 4 with CIM331 compared with -20% with placebo. CIM331 increased sleep efficiency and decreased the use of hydrocortisone butyrate. Conclusions: A single subcutaneous administration of CIM331 was well tolerated in healthy volunteers and patients with AD. It decreased pruritus, sleep disturbance and topical use of hydrocortisone.

AB - Summary: Background: The cytokine interleukin-31 (IL-31) is considered to be responsible for the development of pruritus in humans. At present, no available evidence has been provided on the safety and efficacy of blocking the IL-31 signal in humans for the amelioration of pruritus in atopic dermatitis (AD). CIM331 is a humanized antihuman IL-31 receptor A (IL-31RA) monoclonal antibody, which binds to IL-31RA to inhibit subsequent IL-31 signalling. Objectives: To assess the tolerability, safety, pharmacokinetics and preliminary efficacy of CIM331 in healthy Japanese and white volunteers, and Japanese patients with AD. Methods: In this randomized, double-blind, placebo-controlled phase I/Ib study, CIM331 was administered in a single subcutaneous dose. The primary outcomes were safety and tolerability; the exploratory analysis was efficacy. Results: No deaths, serious adverse events (AEs) or discontinuations due to AEs were reported in any part of the study. No dose-dependent increase in the incidence of AEs occurred in any part of the study. In healthy volunteers, all AEs occurred once in the placebo groups, and increased creatine phosphokinase was more common in the CIM331 groups. In patients with AD, CIM331 reduced pruritus visual analogue scale score to about -50% at week 4 with CIM331 compared with -20% with placebo. CIM331 increased sleep efficiency and decreased the use of hydrocortisone butyrate. Conclusions: A single subcutaneous administration of CIM331 was well tolerated in healthy volunteers and patients with AD. It decreased pruritus, sleep disturbance and topical use of hydrocortisone.

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U2 - 10.1111/bjd.14207

DO - 10.1111/bjd.14207

M3 - Article

C2 - 26409172

AN - SCOPUS:84951744049

JO - British Journal of Dermatology

JF - British Journal of Dermatology

SN - 0007-0963

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