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 (T_RM) 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, T_RM cell numbers in lesional skin were markedly reduced, with numbers similar to non-lesional T_RM 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.