A randomized, placebo-controlled, phase 2 study of the Janus Kinase 1 inhibitor INCB054707 for patients with moderate-to-severe hidradenitis suppurativa
Alavi A, Hamzavi I, Brown K, Santos LL, Zhu Z, Howell MD, and Kirby J. A randomized, placebo-controlled, phase 2 study of the Janus Kinase 1 inhibitor INCB054707 for patients with moderate-to-severe hidradenitis suppurativa. Exp Dermatol 2021; 30(SUPPL 1):69-70.
Background: Janus kinase (JAK)-mediated cytokine signaling contributes to local and systemic inflammation in hidradenitis suppurativa (HS). Objectives: We describe results from a multicenter phase 2 trial of the JAK1 inhibitor INCB054707 in patients with HS.
Methods: This was a placebo-controlled, dose-escalation study; patients received INCB054707 once daily (30-, 60- or 90-mg cohorts) or placebo (3:1 randomization per cohort) for 8 weeks, with a 30-day safety follow-up. Patients aged 18-75 years with moderate-to-severe HS of ≤yen;6-months' duration, lesions in ≤yen;2 anatomic locations (Hurley stage II/III), and total abscess and inflammatory nodule count of ≤yen;3 were eligible. The primary endpoint was safety and tolerability. Additional endpoints included HS Clinical Response (HiSCR), HS quality of life (HiSQoL), and peripheral blood biomarkers.
Results: Thirty-five patients were enrolled (median [range] age, 45.0 [18-64] years; 80% female; 89% white; 71% Hurley stage II at baseline). Nine patients were randomized to placebo and 26 to INCB054707 (30 mg, n = 9; 60 mg, n = 9; 90 mg, n = 8). Overall, 81% of patients receiving INCB054707 had ≤yen;1 treatment-emergent adverse event (TEAE; 12% grade 3, all thrombocytopenia at 90 mg); no discontinuations resulted from TEAEs. More patients receiving 90 mg INCB054707 than placebo had Week 8 HiSCR (88% vs 57%; Figure 1). Mean change from baseline in Week 8 HiSQoL was greater for patients treated with INCB054707 (range across doses, -28.0 to -39.0) vs placebo (-3.4). Biomarker analysis demonstrated dose-dependent differences in the modulation of inflammatory mediators.
Conclusion: INCB054707 was well generally tolerated, demonstrated preliminary efficacy, and improved QoL in patients with moderate-to-severe HS.