Phase 2a, randomized, double-blind, placebo-controlled, multicenter, parallel-group study of a H4R-antagonist (JNJ-39758979) in Japanese adults with moderate atopic dermatitis
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, m...
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Published in | Journal of dermatology Vol. 42; no. 2; pp. 129 - 139 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Tokyo
Blackwell Publishing Ltd
01.02.2015
Wiley Subscription Services, Inc |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | istex:4834CC925129DC0C788CECE3A5D893C945E75E40 ArticleID:JDE12726 ark:/67375/WNG-RQZ15ZZH-0 Figure S1. Mean changes from baseline to week 6 in Pruritus Categorical Response Scale (PCRS) Daytime Pruritus Severity (A), PCRS Night-time Pruritus Severity (B), Pruritus Numeric Rating Scales (PNRS) Daytime Pruritus Severity (C), PNRS Daytime Pruritus Duration (D), Pruritus Interference Numeric Rating Scale (PINRS) Impact of Pruritus on Daily Activity (E) and PINRS Impact of Pruritus on Sleep (F). Figure S2. Structures of known JNJ-39758979 metabolites assessed in the study. Table S1. Whole blood and plasma concentrations of JNJ-39758979 and known metabolites (M3, M5, M12 and M13) Janssen Pharmaceutical and Janssen Research and Development |
ISSN: | 0385-2407 1346-8138 |
DOI: | 10.1111/1346-8138.12726 |