TYK2/JAK1 Inhibitor PF-06700841 in Patients with Plaque Psoriasis: Phase IIa, Randomized, Double-Blind, Placebo-Controlled Trial.

Abstract

TRIAL DESIGN:

We report results from a phase IIa study of efficacy and safety of PF-06700841, an oral TYK2/Jak1 inhibitor, in patients with moderate-to-severe plaque psoriasis (NCT02969018).

METHODS:

Patients were randomized to PF-06700841 30 mg once daily (QD), 60 mg QD, or placebo (4-week induction), followed by 10 mg QD, 30 mg QD, 100 mg once weekly, or placebo (8-week maintenance). The primary endpoint was week 12 change from baseline in PASI score. Secondary endpoints were the proportion of patients achieving 75% and 90% reduction from baseline PASI at week 12.

RESULTS:

In total, 212 patients in 35 sites were treated; mean (SD) baseline PASI score was 20.8 (7.68). Decreases in PASI at week 12 were statistically significant compared with placebo in five treatment groups. The greatest change from baseline (least squares mean change -17.3 [95% confidence interval, -20.0 to -14.6]) was observed in the 30-mg QD continuous treatment group. Overall, 136 patients experienced treatment-emergent adverse events, including six serious adverse events in five patients and 13 discontinuations in treatment groups because of adverse events. No herpes zoster cases or major adverse cardiac events including thromboembolic events occurred.

CONCLUSIONS:

PF-06700841 was generally effective and well tolerated in patients with moderate-to-severe plaque psoriasis.

• Authors: Seth B Forman, David M Pariser, Yves Poulin, Michael S Vincent, Steven A Gilbert, Elizabeth M Kieras, Ruolun Qiu, Dahong Yu, Jocelyne Papacharalambous, Christopher Tehlirian, Elena Peeva
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 140 Issue 12 Pg. 2359-2370.e5 (12 2020) ISSN: 1523-1747 [Electronic] United States
• PMID: 32311398 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Placebos
• Protein Kinase Inhibitors
• Pyrazoles
• Pyrimidines
• PF-06700841
• JAK1 protein, human
• Janus Kinase 1
• TYK2 Kinase
• TYK2 protein, human

Topics

• Adult
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Administration Schedule
• Female
• Follow-Up Studies
• Humans
• Janus Kinase 1 (antagonists & inhibitors)
• Male
• Middle Aged
• Placebos (administration & dosage, adverse effects)
• Protein Kinase Inhibitors (administration & dosage, adverse effects, pharmacokinetics)
• Psoriasis (diagnosis, drug therapy)
• Pyrazoles (administration & dosage, adverse effects, pharmacokinetics)
• Pyrimidines (administration & dosage, adverse effects, pharmacokinetics)
• Remission Induction (methods)
• Severity of Illness Index
• TYK2 Kinase (antagonists & inhibitors)
• Treatment Outcome