The efficacy, safety and pharmacokinetics of IL-17A monoclonal antibody injection (AK111) in patients with moderate to severe plaque psoriasis: a randomized, double-blind, placebo-controlled phase Ib multi-dose escalation clinical study

Objectives: To evaluate the safety, tolerability, immunogenicity, pharmacokinetics (PK), pharmacodynamics (PD), and the expression of skin biomarkers of AK111 injection after multiple administration in subjects with moderate to severe plaque psoriasis, and to evaluate the preliminary clinical efficacy in the trial. Methods: This study is a randomized, double-blind, placebo-parallel controlled study using a dose escalation mode of multiple doses. 48 subjects were sequentially randomized to receive each of AK111 dose regimens (75mg, 150mg, 300mg, 450mg) or corresponding placebo. All subjects were treated with the study drug at week 0/1/4/8 and were unblinded at week 12 with the placebo group being ended, and AK111 group being followed up to 20 weeks. Results: A total of 48 subjects were randomized. At week 12, compared with placebo, the percentage of subjects achieving PASI75 and sPGA0/1 in AK111 75mg, 150mg, 300mg, and 450mg dose groups was significantly increased, and higher PASI90 was achieved in 150mg, 300mg, and 450mg dose groups than in 75mg group. All efficacy indicators were maintained at week 20. The incidence of treatment-emergent Anti-Drug Antibody (ADA) was 0%(0/48). Neutralizing antibodies (Nabs) were not detected in any subject. The proportion of subjects with any reported treatment-emergent adverse event (TEAE) was 75.0% in the AK111 group, similar to 66.7% in the placebo group, and there was no obvious dose relationship. The most commonly reported adverse events were hyperglycemia, elevated blood pressure and hypokalemia. Additionally, the AK111 PK showed approximate dose proportionalitywith regard to the PK parameters of the Cmax and AUC0-tfollowing subcutaneous injection doses of 150mg,300mg and 450 mg. Conclusion: After moderate to severe plaque psoriasis subjects received multiple subcutaneous AK111 injections,the dose range of 150mg-450mg, AK111 exposure increased in an approximate dose-proportional relationship. AK111 was demonstrated to be safe and tolerable. In subjects with moderate to severe plaque psoriasis, AK111 demonstrated encouraging preliminary efficacy which was sustained in a relatively long period after the last dose administration. Clinical trial registration Clinical trial identification number is NCT05504317 and was registered in August 2022