Journal of the American Academy of Dermatology · 2025
Highly selective, allosteric inhibition of TYK2 with oral ESK-001 in patients with moderate-to-severe plaque psoriasis: Results from STRIDE, a 12-week, randomized, double-blinded, placebo-controlled, dose-ranging phase 2 study.
СтатьяРандомизированное исследованиеКлиническое исследование II фазыМногоцентровое исследованиеПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Blauvelt Andrew, Arenberger Petr, Sauder Maxwell B, Couvillion Megan, Rubio Roman G, Vlahakis Nicholas E, Ucpinar Sibel, Ma Grace, Hitraya Elena, Tilley Mera K, Papp Kim A, STRIDE Investigators
Аннотация
BACKGROUND: ESK-001, a novel allosteric, highly selective oral tyrosine kinase 2 inhibitor in development for treatment of immune-mediated disorders, was well-tolerated and achieved high levels of target inhibition in phase 1 studies with healthy volunteers.
OBJECTIVE: To assess clinical efficacy, safety, and pharmacokinetics of ESK-001 compared to placebo in patients with moderate-to-severe plaque psoriasis.
METHODS: STRIDE (NCT05600036, EudraCT Number 2022-002633-34) was a phase 2, double-blinded, 16-week study with patients randomized to 6 treatment groups for 12 weeks of placebo or ESK-001, ranging from 10 mg QD to 40 mg BID.
RESULTS: ESK-001 demonstrated a dose-dependent improvement across all end points, with maximal efficacy observed in the highest dose arm (40 mg BID). At week 12, more patients achieved Psoriasis Area and Severity Index-75 in each ESK-001 dose arm compared to placebo: 64% in the 40 mg BID arm vs 0% with placebo (P < .0001). ESK-001 was well-tolerated, with no dose-limiting safety findings and a 2.6% rate of ESK-001 discontinuation due to adverse events.
LIMITATIONS: Small sample size per treatment group and 16-week study duration.
CONCLUSION: ESK-001 demonstrated significant dose-dependent improvement in signs and symptoms of psoriasis while achieving continuous target inhibition at the highest dose in patients with psoriasis and was well-tolerated.
OBJECTIVE: To assess clinical efficacy, safety, and pharmacokinetics of ESK-001 compared to placebo in patients with moderate-to-severe plaque psoriasis.
METHODS: STRIDE (NCT05600036, EudraCT Number 2022-002633-34) was a phase 2, double-blinded, 16-week study with patients randomized to 6 treatment groups for 12 weeks of placebo or ESK-001, ranging from 10 mg QD to 40 mg BID.
RESULTS: ESK-001 demonstrated a dose-dependent improvement across all end points, with maximal efficacy observed in the highest dose arm (40 mg BID). At week 12, more patients achieved Psoriasis Area and Severity Index-75 in each ESK-001 dose arm compared to placebo: 64% in the 40 mg BID arm vs 0% with placebo (P < .0001). ESK-001 was well-tolerated, with no dose-limiting safety findings and a 2.6% rate of ESK-001 discontinuation due to adverse events.
LIMITATIONS: Small sample size per treatment group and 16-week study duration.
CONCLUSION: ESK-001 demonstrated significant dose-dependent improvement in signs and symptoms of psoriasis while achieving continuous target inhibition at the highest dose in patients with psoriasis and was well-tolerated.