Format

Send to:

Choose Destination
See comment in PubMed Commons below
Br J Dermatol. 2015 Feb 21. doi: 10.1111/bjd.13745. [Epub ahead of print]

A phase 2a randomized, double-blind, placebo-controlled, sequential dose-escalation study to evaluate the efficacy and safety of ASP015K, a novel Janus kinase inhibitor, in patients with moderate-to-severe psoriasis.

Author information

  • 1Probity Medical Research, Waterloo, ON, Canada.
  • 2Eastern Virginia Medical School and Virginia Clinical Research, Inc., Norfolk, VA, U.S.A.
  • 3MEDTOX Scientific, Inc., St. Paul, MN, U.S.A.
  • 4Astellas Pharma Global Development, Northbrook, IL, U.S.A.
  • 5The Rockefeller University, New York, NY, U.S.A.

Abstract

BACKGROUND:

Many immune-mediated disorders, including psoriasis, involve cytokine signalling via Janus kinase (JAK) enzymes. ASP015K (also designated JNJ-54781532), a novel oral JAK inhibitor, has shown moderate selectivity for JAK3 over JAK1 and JAK2 in enzyme assays.

OBJECTIVES:

The objective of this study was to evaluate the efficacy and safety of escalating, sequentially grouped, doses of ASP015K vs. placebo in patients with moderate-to-severe psoriasis.

METHODS:

This phase 2a multicentre, double-blind, randomized, placebo-controlled study (NCT01096862) enrolled 124 patients with moderate-to-severe plaque psoriasis. Five sequential ASP015K cohorts were enrolled, consisting of four twice-daily dosing groups (10, 25, 60, 100 mg) and one once-daily dosing group (50 mg) for 6 weeks.

RESULTS:

The primary efficacy end point [mean change in Psoriasis Area and Severity Index score from baseline to end of treatment (EOT; day 42)] significantly favoured ASP015K (overall treatment effect; P < 0·001) vs. placebo, with greater improvements at higher doses. By EOT, the secondary end points [Physician Static Global Assessment (PSGA) score, percentage of patients achieving PSGA success, and change in percentage, body surface area (BSA)] also improved with ASP015K vs. placebo (P < 0·001 for PSGA score and BSA; P < 0·01 for PSGA success). Epidermal thickness and proliferation decreased from baseline with ASP015K vs. placebo. ASP015K was generally well tolerated, with no serious adverse events (AEs) reported.

CONCLUSIONS:

In patients with moderate-to-severe psoriasis, ASP015K demonstrated dose-dependent improvements in clinical and histological measures of severity over 6 weeks of treatment. At all doses, ASP015K was well tolerated, with no reported serious AEs.

© 2015 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.

PMID:
25704750
[PubMed - as supplied by publisher]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Blackwell Publishing
    Loading ...
    Write to the Help Desk