Phase 2a, randomized, double-blind, placebo-controlled, multicenter, parallel-group study of a H4R-antagonist (JNJ-39758979) in Japanese adults with moderate atopic dermatitis

Yoko Murata, Michael Song, Hisayuki Kikuchi, Katsuya Hisamichi, Xie L. Xu, Andrew Greenspan, Mai Kato, Chiun Fang Chiou, Takeshi Kato, Cynthia Guzzo, Robin L. Thurmond, Mamitaro Ohtsuki, Masutaka Furue

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

This trial was conducted to evaluate the safety and efficacy of the H4R-antagonist JNJ-39758979 in adult Japanese patients with moderate atopic dermatitis (AD). Eligible patients were randomly assigned to JNJ-39758979 300 mg, 100 mg or placebo once daily for 6 weeks in this phase 2a, double-blind, multicenter, placebo-controlled study. Primary efficacy was assessed via week-6 Eczema Area and Severity Index (EASI) scores. Secondary efficacy assessments included Investigator's Global Assessment (IGA) and patient-reported outcome (PRO) pruritus assessments (Pruritus Categorical Response Scale [PCRS], Pruritus Numeric Rating Scales [PNRS], Pruritus Interference Numeric Rating Scale [PINRS] and Subject's Global Impressions of Change in Pruritus [SGICP]). Eighty-eight of 105 planned patients were randomized before the study was stopped and unblinded for safety reasons. The study did not meet the primary end-point. However, numerical improvements (i.e. decreases) in median EASI were observed with JNJ-39758979 100 mg (-3.7) and 300 mg (-3.0) versus placebo (-1.3) at week 6. Nominally significant improvements across PRO PCRS, PNRS and SGICP assessments were consistently observed, particularly with JNJ-39758979 300 mg. Safety, including adverse events (AE), was comparable between JNJ-39758979 and placebo with the exception of two patients (both receiving JNJ-39758979 300 mg) with serious AE of neutropenia, leading to premature study discontinuation. No deaths were reported. Except for neutropenia, no clinically relevant changes in laboratory values were observed. Although not conclusive, findings suggest H4R-antagonism may be beneficial for AD, particularly in controlling pruritus. JNJ-39758979 appears to be associated with drug-induced agranulocytosis, likely an off-target effect.

Original languageEnglish
Pages (from-to)129-139
Number of pages11
JournalJournal of Dermatology
Volume42
Issue number2
DOIs
Publication statusPublished - Feb 1 2015

Fingerprint

Atopic Dermatitis
Pruritus
Placebos
Eczema
Neutropenia
Safety
4-(3-aminopyrrolidin-1-yl)-6-isopropylpyrimidin-2-ylamine
Agranulocytosis
Research Personnel
Outcome Assessment (Health Care)
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Dermatology

Cite this

Phase 2a, randomized, double-blind, placebo-controlled, multicenter, parallel-group study of a H4R-antagonist (JNJ-39758979) in Japanese adults with moderate atopic dermatitis. / Murata, Yoko; Song, Michael; Kikuchi, Hisayuki; Hisamichi, Katsuya; Xu, Xie L.; Greenspan, Andrew; Kato, Mai; Chiou, Chiun Fang; Kato, Takeshi; Guzzo, Cynthia; Thurmond, Robin L.; Ohtsuki, Mamitaro; Furue, Masutaka.

In: Journal of Dermatology, Vol. 42, No. 2, 01.02.2015, p. 129-139.

Research output: Contribution to journalArticle

Murata, Y, Song, M, Kikuchi, H, Hisamichi, K, Xu, XL, Greenspan, A, Kato, M, Chiou, CF, Kato, T, Guzzo, C, Thurmond, RL, Ohtsuki, M & Furue, M 2015, 'Phase 2a, randomized, double-blind, placebo-controlled, multicenter, parallel-group study of a H4R-antagonist (JNJ-39758979) in Japanese adults with moderate atopic dermatitis', Journal of Dermatology, vol. 42, no. 2, pp. 129-139. https://doi.org/10.1111/1346-8138.12726
Murata, Yoko ; Song, Michael ; Kikuchi, Hisayuki ; Hisamichi, Katsuya ; Xu, Xie L. ; Greenspan, Andrew ; Kato, Mai ; Chiou, Chiun Fang ; Kato, Takeshi ; Guzzo, Cynthia ; Thurmond, Robin L. ; Ohtsuki, Mamitaro ; Furue, Masutaka. / Phase 2a, randomized, double-blind, placebo-controlled, multicenter, parallel-group study of a H4R-antagonist (JNJ-39758979) in Japanese adults with moderate atopic dermatitis. In: Journal of Dermatology. 2015 ; Vol. 42, No. 2. pp. 129-139.
@article{2b54fdc3660f4caabf0d6d8b67afabb6,
title = "Phase 2a, randomized, double-blind, placebo-controlled, multicenter, parallel-group study of a H4R-antagonist (JNJ-39758979) in Japanese adults with moderate atopic dermatitis",
abstract = "This trial was conducted to evaluate the safety and efficacy of the H4R-antagonist JNJ-39758979 in adult Japanese patients with moderate atopic dermatitis (AD). Eligible patients were randomly assigned to JNJ-39758979 300 mg, 100 mg or placebo once daily for 6 weeks in this phase 2a, double-blind, multicenter, placebo-controlled study. Primary efficacy was assessed via week-6 Eczema Area and Severity Index (EASI) scores. Secondary efficacy assessments included Investigator's Global Assessment (IGA) and patient-reported outcome (PRO) pruritus assessments (Pruritus Categorical Response Scale [PCRS], Pruritus Numeric Rating Scales [PNRS], Pruritus Interference Numeric Rating Scale [PINRS] and Subject's Global Impressions of Change in Pruritus [SGICP]). Eighty-eight of 105 planned patients were randomized before the study was stopped and unblinded for safety reasons. The study did not meet the primary end-point. However, numerical improvements (i.e. decreases) in median EASI were observed with JNJ-39758979 100 mg (-3.7) and 300 mg (-3.0) versus placebo (-1.3) at week 6. Nominally significant improvements across PRO PCRS, PNRS and SGICP assessments were consistently observed, particularly with JNJ-39758979 300 mg. Safety, including adverse events (AE), was comparable between JNJ-39758979 and placebo with the exception of two patients (both receiving JNJ-39758979 300 mg) with serious AE of neutropenia, leading to premature study discontinuation. No deaths were reported. Except for neutropenia, no clinically relevant changes in laboratory values were observed. Although not conclusive, findings suggest H4R-antagonism may be beneficial for AD, particularly in controlling pruritus. JNJ-39758979 appears to be associated with drug-induced agranulocytosis, likely an off-target effect.",
author = "Yoko Murata and Michael Song and Hisayuki Kikuchi and Katsuya Hisamichi and Xu, {Xie L.} and Andrew Greenspan and Mai Kato and Chiou, {Chiun Fang} and Takeshi Kato and Cynthia Guzzo and Thurmond, {Robin L.} and Mamitaro Ohtsuki and Masutaka Furue",
year = "2015",
month = "2",
day = "1",
doi = "10.1111/1346-8138.12726",
language = "English",
volume = "42",
pages = "129--139",
journal = "Journal of Dermatology",
issn = "0385-2407",
publisher = "Wiley-Blackwell",
number = "2",

}

TY - JOUR

T1 - Phase 2a, randomized, double-blind, placebo-controlled, multicenter, parallel-group study of a H4R-antagonist (JNJ-39758979) in Japanese adults with moderate atopic dermatitis

AU - Murata, Yoko

AU - Song, Michael

AU - Kikuchi, Hisayuki

AU - Hisamichi, Katsuya

AU - Xu, Xie L.

AU - Greenspan, Andrew

AU - Kato, Mai

AU - Chiou, Chiun Fang

AU - Kato, Takeshi

AU - Guzzo, Cynthia

AU - Thurmond, Robin L.

AU - Ohtsuki, Mamitaro

AU - Furue, Masutaka

PY - 2015/2/1

Y1 - 2015/2/1

N2 - This trial was conducted to evaluate the safety and efficacy of the H4R-antagonist JNJ-39758979 in adult Japanese patients with moderate atopic dermatitis (AD). Eligible patients were randomly assigned to JNJ-39758979 300 mg, 100 mg or placebo once daily for 6 weeks in this phase 2a, double-blind, multicenter, placebo-controlled study. Primary efficacy was assessed via week-6 Eczema Area and Severity Index (EASI) scores. Secondary efficacy assessments included Investigator's Global Assessment (IGA) and patient-reported outcome (PRO) pruritus assessments (Pruritus Categorical Response Scale [PCRS], Pruritus Numeric Rating Scales [PNRS], Pruritus Interference Numeric Rating Scale [PINRS] and Subject's Global Impressions of Change in Pruritus [SGICP]). Eighty-eight of 105 planned patients were randomized before the study was stopped and unblinded for safety reasons. The study did not meet the primary end-point. However, numerical improvements (i.e. decreases) in median EASI were observed with JNJ-39758979 100 mg (-3.7) and 300 mg (-3.0) versus placebo (-1.3) at week 6. Nominally significant improvements across PRO PCRS, PNRS and SGICP assessments were consistently observed, particularly with JNJ-39758979 300 mg. Safety, including adverse events (AE), was comparable between JNJ-39758979 and placebo with the exception of two patients (both receiving JNJ-39758979 300 mg) with serious AE of neutropenia, leading to premature study discontinuation. No deaths were reported. Except for neutropenia, no clinically relevant changes in laboratory values were observed. Although not conclusive, findings suggest H4R-antagonism may be beneficial for AD, particularly in controlling pruritus. JNJ-39758979 appears to be associated with drug-induced agranulocytosis, likely an off-target effect.

AB - This trial was conducted to evaluate the safety and efficacy of the H4R-antagonist JNJ-39758979 in adult Japanese patients with moderate atopic dermatitis (AD). Eligible patients were randomly assigned to JNJ-39758979 300 mg, 100 mg or placebo once daily for 6 weeks in this phase 2a, double-blind, multicenter, placebo-controlled study. Primary efficacy was assessed via week-6 Eczema Area and Severity Index (EASI) scores. Secondary efficacy assessments included Investigator's Global Assessment (IGA) and patient-reported outcome (PRO) pruritus assessments (Pruritus Categorical Response Scale [PCRS], Pruritus Numeric Rating Scales [PNRS], Pruritus Interference Numeric Rating Scale [PINRS] and Subject's Global Impressions of Change in Pruritus [SGICP]). Eighty-eight of 105 planned patients were randomized before the study was stopped and unblinded for safety reasons. The study did not meet the primary end-point. However, numerical improvements (i.e. decreases) in median EASI were observed with JNJ-39758979 100 mg (-3.7) and 300 mg (-3.0) versus placebo (-1.3) at week 6. Nominally significant improvements across PRO PCRS, PNRS and SGICP assessments were consistently observed, particularly with JNJ-39758979 300 mg. Safety, including adverse events (AE), was comparable between JNJ-39758979 and placebo with the exception of two patients (both receiving JNJ-39758979 300 mg) with serious AE of neutropenia, leading to premature study discontinuation. No deaths were reported. Except for neutropenia, no clinically relevant changes in laboratory values were observed. Although not conclusive, findings suggest H4R-antagonism may be beneficial for AD, particularly in controlling pruritus. JNJ-39758979 appears to be associated with drug-induced agranulocytosis, likely an off-target effect.

UR - http://www.scopus.com/inward/record.url?scp=84922696048&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84922696048&partnerID=8YFLogxK

U2 - 10.1111/1346-8138.12726

DO - 10.1111/1346-8138.12726

M3 - Article

VL - 42

SP - 129

EP - 139

JO - Journal of Dermatology

JF - Journal of Dermatology

SN - 0385-2407

IS - 2

ER -