K Papp1, D Thaçi2, K Reich3, E Riedl4, R G Langley5, J G Krueger6, A B Gottlieb7, H Nakagawa8, E P Bowman9, A Mehta9, Q Li9, Y Zhou9, R Shames9. 1. Probity Medical Research, 135 Union Street East, Waterloo, ON, N2J 1C4, Canada. 2. Comprehensive Center for Inflammation Medicine, University Medical School Schleswig-Holstein, University of Lübeck, Lübeck, Germany. 3. SCIderm Research Institute and Dermatologikum Hamburg, Hamburg, Germany. 4. Division of General Dermatology, Department of Dermatology, Medical University of Vienna, Vienna, Austria. 5. Dalhousie University, Halifax, NS, Canada. 6. Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY, U.S.A. 7. Department of Dermatology, Tufts Medical Center, Boston, MA, U.S.A. 8. Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan. 9. Merck & Co., Inc., Kenilworth, NJ, U.S.A.
Abstract
BACKGROUND:Tildrakizumab is a high-affinity, humanized, IgG1/κ, anti-interleukin (IL)-23p19 monoclonal antibody that does not bind human IL-12 or p40 is being developed for the treatment of chronic plaque psoriasis. OBJECTIVES: To evaluate the safety and efficacy of subcutaneous tildrakizumab in patients with moderate-to-severe chronic plaque psoriasis. METHODS: A three-part, randomized, double-blind, phase IIb trial was conducted in 355 adults with chronic plaque psoriasis. Participants were randomized to receive subcutaneous tildrakizumab (5, 25, 100, 200 mg) or placebo at weeks 0 and 4 (part I) and every 12 weeks thereafter until week 52 (part II). Study drug was discontinued at week 52 and participants were followed through week 72 (part III). Primary efficacy end point was Psoriasis Area and Severity Index (PASI) 75 response at week 16. Adverse events (AEs) and vital signs were monitored throughout the study. RESULTS: At week 16, PASI 75 responses were 33·3% (n = 14), 64·4% (n = 58), 66·3% (n = 59), 74·4% (n = 64) and 4·4% (n = 2) in the 5-, 25-, 100- and 200-mg tildrakizumab and placebo groups, respectively (P ≤ 0·001 for each tildrakizumab dose vs. placebo). PASI 75 response was generally maintained through week 52; only eight of 222 participants who achieved PASI 75 response at week 52 and continued to part III relapsed following discontinuation up to week 72. Possible drug-related serious AEs included bacterial arthritis and lymphoedema (part I), and melanoma, stroke, epiglottitis and knee infection (part II). CONCLUSIONS:Tildrakizumab had treatment effects that were superior to placebo, maintained for 52 weeks of treatment, and persisted for 20 weeks after cessation. Tildrakizumab was generally safe and well tolerated. These results suggest that IL-23p19 is a key target for suppressing psoriasis.
RCT Entities:
BACKGROUND:Tildrakizumab is a high-affinity, humanized, IgG1/κ, anti-interleukin (IL)-23p19 monoclonal antibody that does not bind human IL-12 or p40 is being developed for the treatment of chronic plaque psoriasis. OBJECTIVES: To evaluate the safety and efficacy of subcutaneous tildrakizumab in patients with moderate-to-severe chronic plaque psoriasis. METHODS: A three-part, randomized, double-blind, phase IIb trial was conducted in 355 adults with chronic plaque psoriasis. Participants were randomized to receive subcutaneous tildrakizumab (5, 25, 100, 200 mg) or placebo at weeks 0 and 4 (part I) and every 12 weeks thereafter until week 52 (part II). Study drug was discontinued at week 52 and participants were followed through week 72 (part III). Primary efficacy end point was Psoriasis Area and Severity Index (PASI) 75 response at week 16. Adverse events (AEs) and vital signs were monitored throughout the study. RESULTS: At week 16, PASI 75 responses were 33·3% (n = 14), 64·4% (n = 58), 66·3% (n = 59), 74·4% (n = 64) and 4·4% (n = 2) in the 5-, 25-, 100- and 200-mg tildrakizumab and placebo groups, respectively (P ≤ 0·001 for each tildrakizumab dose vs. placebo). PASI 75 response was generally maintained through week 52; only eight of 222 participants who achieved PASI 75 response at week 52 and continued to part III relapsed following discontinuation up to week 72. Possible drug-related serious AEs included bacterial arthritis and lymphoedema (part I), and melanoma, stroke, epiglottitis and knee infection (part II). CONCLUSIONS:Tildrakizumab had treatment effects that were superior to placebo, maintained for 52 weeks of treatment, and persisted for 20 weeks after cessation. Tildrakizumab was generally safe and well tolerated. These results suggest that IL-23p19 is a key target for suppressing psoriasis.
Authors: George Martin; Bruce E Strober; Craig L Leonardi; Joel M Gelfand; Andrew Blauvelt; Arthur Kavanaugh; Linda Stein Gold; Brian Berman; Ted Rosen; Eggert Stockfleth Journal: J Clin Aesthet Dermatol Date: 2016-09-01
Authors: Cristina Sayago; Isabel C Gonzalez Valcarcel; Yuewei Qian; John Lee; Jorge Alsina-Fernandez; Nathan C Fite; Juan J Carrillo; Feiyu F Zhang; Michael J Chalmers; Jeffrey A Dodge; Howard Broughton; Alfonso Espada Journal: ACS Med Chem Lett Date: 2018-08-01 Impact factor: 4.345