LB1703 High induction dosing of risankizumab in patients with moderate-to-severe plaque psoriasis: Interim results from the phase 2 KNOCKOUT study

Objective: Evaluate safety and efficacy of high induction doses of risankizumab (RZB) in patients with moderate-to-severe plaque psoriasis at week 16. Risankizumab, a humanized IgG1 monoclonal antibody that inhibits the interleukin (IL)-23 p19 subunit, is approved to treat moderate-to-severe plaque psoriasis. KNOCKOUT (NCT05283135) is an ongoing phase 2, double-blinded, single-center study evaluating whether higher-than-approved RZB induction doses are effective in achieving and sustaining clearance of psoriasis following drug cessation. Numbers of resident memory T cells (Trm), which depend on IL-23 for survival, are also being assessed. Patients with moderate-to-severe plaque psoriasis were randomized 1:1 to receive RZB 300 mg or 600 mg subcutaneously at weeks 0, 4, and 16 and will be followed long term with no additional RZB dosing. We report a blinded interim assessment of safety and efficacy at week 16 (after 2 doses of RZB; cutoff date December 2, 2022), including mean percent improvement from baseline in Psoriasis Area and Severity Index (PASI) and proportions of patients who achieved ≥75%/≥90%/100% PASI improvement (observed cases). KNOCKOUT enrolled 20 patients; 18 completed dosing and were included in efficacy analyses. At week 16, mean (95% CI) percent improvement from baseline in PASI in the combined 300 mg/600 mg groups was 97.5% (94.8%, 100%), and 100%/94.4%/66.7% of patients achieved PASI 75/90/100. Incidence of adverse events was low and similar to previous RZB studies in psoriasis. In conclusion, high RZB induction doses were well-tolerated; two-thirds of patients achieved complete skin clearance after 2 doses at week 16. Ongoing long-term assessments will evaluate clinical effects following the third RZB dose, maintenance of efficacy after RZB cessation, and Trm numbers.