Safety and Efficacy of Anti-IL-23 Monoclonal Antibody QX004N for Patients With Psoriasis: A Randomized Clinical Trial.

Importance: Psoriasis is a chronic, immune-mediated skin disease with an unmet need for biologic treatment options.

Objective: To assess the safety, pharmacokinetics, and efficacy of QX004N in healthy individuals and patients with moderate to severe plaque psoriasis in China.

Design, setting, and participants: This randomized clinical trial was composed of 2 parts. Part 1 was a first-in-human, single-ascending-dose, phase 1a clinical trial conducted from November 2, 2021, to January 16, 2023. Part 2 was a double-blind, multiple dose-escalation, phase 1b clinical trial conducted from February 15, 2023, to January 5, 2024, at 5 clinical centers in China, involving patients with moderate to severe plaque psoriasis.

Interventions: In part 1, healthy participants in each cohort were assigned in a 4:1 ratio to receive a single subcutaneous injection of QX004N (ranging from 10 mg to 600 mg) or placebo. In part 2, patients in each cohort were assigned in a 4:1 ratio to receive QX004N or placebo at doses of 150 mg, 300 mg, and 600 mg once every 2 weeks.

Main outcomes and measures: For part 1, the primary outcome was the safety of a single dose of QX004N in healthy participants, and the secondary outcome was the pharmacokinetic profile. For part 2, the primary efficacy end point was the proportion of patients achieving at least 75% improvement in Psoriasis Area and Severity Index (PASI 75) by week 12; other efficacy end points were considered secondary.

Results: The phase 1a clinical trial (part 1) enrolled 55 healthy participants (mean [SD] age, 35.9 [6.0] years; 30 [54.5%] female), and the phase 1b clinical trial (part 2) enrolled 30 patients with moderate to severe plaque psoriasis. The mean (SD) age of QX004N-treated participants in part 2 was 41.4 (7.5) years, and 19 of 24 QX004N-treated participants (79.2%) were male. The mean (SD) age of the placebo cohort in part 2 was 35.3 (8.4) years, and 5 of 6 placebo-treated participants (83.3%) were male. QX004N exhibited linear pharmacokinetics and was tolerated well in both healthy participants and patients with psoriasis. Most adverse events were mild to moderate in severity, with no drug-related serious adverse events reported. The proportion of patients receiving QX004N who achieved PASI 75 at week 12 and PASI 90 (90% improvement in PASI) at week 16 in the 150-mg, 300-mg, and 600-mg cohorts was 100%, significantly higher than that in the placebo cohorts (33.3%). The maximum proportion of patients achieving Investigator's Global Assessment score of 0 or 1 was 100% in the 3 QX004N cohorts.

Conclusions and relevance: In this randomized clinical trial, QX004N was well tolerated and demonstrated superior efficacy compared to placebo in patients with moderate to severe plaque psoriasis.

Trial registration: Chinese Clinical Trial Registry Identifier: CTR20212313 and CTR20223457.