Safety and efficacy of the selective tyrosine kinase 2/Janus kinase 1 inhibitor TLL-018 in moderate-to-severe plaque psoriasis: a phase Ib, randomized, double-blind, placebo-controlled study.

BACKGROUND

Psoriasis treatments that provide rapid and extensive itch relief as well as lesion clearance are currently inadequate.

OBJECTIVES

To evaluate the efficacy and safety of the tyrosine kinase 2/Janus kinase 1 inhibitor TLL-018 in patients with moderate-to-severe psoriasis.

METHODS

This phase Ib, double-blind, placebo-controlled study (NCT05342428) randomized participants to receive TLL-018 10 mg, 20 mg, 30 mg or placebo 2 : 2 : 2 : 1 orally twice daily for 12 weeks. The study included 73 patients with moderate-to-severe psoriasis. Eligible patients were aged 18-75 years and were diagnosed with moderate-to-severe psoriasis at least 6 months prior to screening, as defined by a Psoriasis Area and Severity Index (PASI) of ≥ 12, a body surface area ≥ 10% and a Physician's Global Assessment (PGA) of ≥ 3. The primary endpoint was safety of TLL-018. The efficacy endpoints were proportions of patients at week 12 achieving a ≥ 75% improvement from baseline in PASI (PASI 75), PGA of 0 or 1 (PGA 0/1) and Dermatology Life Quality Index of 0 or 1.

RESULTS

A total of 73 participants were treated. TLL-018 was well tolerated, and most treatment-emergent adverse events were mild/moderate. At week 12, 40% of patients (8 of 20) achieved PASI 75 with TLL-018 10 mg, 48% (10 of 21) with 20 mg, 62% (13 of 21) with 30 mg and 9% (1 of 11) with placebo. The proportions of patients with PGA 0/1 were 35%, 43%, 71% and 0%, respectively. Of the 21 patients in the TLL-018 30-mg group, 10 (48%) achieved a ≥ 90% improvement from baseline in PASI.

CONCLUSIONS

TLL-018 was well tolerated and showed promising efficacy at week 12 compared with placebo in patients with moderate-to-severe plaque psoriasis.