A randomized phase 2 clinical trial to treat moderate-to-severe plaque psoriasis patients with high-induction dosing of risankizumab

The phase 2 KNOCKOUT (NCT05283135) study evaluates higher-than-approved doses of risankizumab, an interleukin-23 inhibitor, for treatment of moderate-to-severe plaque psoriasis. Patients received either 300 or 600 mg of risankizumab at Weeks 0, 4, and 16 and were monitored for 100 weeks without further dosing. Efficacy and safety were tracked throughout the study and lesional/non-lesional tissue was evaluated by RNASeq. The primary endpoint was the change in baseline in number and/or function of tissue resident memory T cells (TRM) at week 52. The secondary endpoints were Psoriasis Areas and Severity Index (PASI) 100 at weeks 28, 40, and 52 and safety events over 100 weeks. Nine patients per treatment group completed dosing. At Weeks 28 and 52, PASI 75/90/100 responses were: 94.4%/94.4%/83.3% and 77.8%/61.1%/44.4% of all patients, respectively, with no new safety signals. At Week 52, TRM cell numbers in lesional skin were markedly reduced, with numbers similar to non-lesional TRM numbers at Week 0. High skin clearance rates with higher-than-approved initial dosing of risankizumab with prolonged maintenance of skin clearance, despite the lack of continuous dosing, represent a potential alternative treatment strategy for patients with psoriasis. Psoriasis is a difficult to treat chronic skin condition that could be limiting to quality of life. Here, authors present results of the phase 2 randomized clinical trial KNOCKOUT (NCT05283135) in which they treated patients with moderate-to-severe plaque psoriasis with higher-than-approved doses of risankizumab, an interleukin-23 inhibitor, to show high skin clearance rates and decreased tissue resident memory T cell numbers in the lesional skin.