Safety, Tolerability, Pharmacokinetics, and Immunogenicity of the Anti-IFNAR1 Monoclonal Antibody QX006N: A First-in-Human Single Ascending Dose Study in Healthy Chinese Volunteers.

Abstract

Background and objective: QX006N is a novel, humanized, IgG4κ monoclonal antibody targeting IFNAR1, developed for the treatment of systemic lupus erythematosus. This study aims to investigate the pharmacokinetics, safety, tolerability, and immunogenicity of QX006N when administered intravenously to healthy Chinese individuals.

Methods: A double-blind, randomized, placebo-controlled, single-ascending-dose, phase I clinical trial was conducted comprising five cohorts (n = 10 per cohort, except n = 5 for the first cohort). Subjects in each cohort were randomly assigned in a 4:1 ratio to receive a single intravenous infusion of QX006N (0.3 mg/kg, 1.0 mg/kg, 3.0 mg/kg, 6.0 mg/kg, or 10.0 mg/kg) or placebo for 30 minutes. Tolerability assessments included adverse events, vital signs, 12-lead electrocardiogram, physical examination, and clinical laboratory tests. The serum concentration of QX006N was measured using the enzyme-linked immunosorbent assay method, and the anti-drug antibodies were detected using the electrochemiluminescence assay method.

Results: QX006N demonstrated a favorable safety and tolerability profile throughout the study. All treatment-emergent adverse events were of Grade 1-2 (CTCAE Version 5.0), and no serious adverse events, deaths, or drug discontinuations because of treatment-emergent adverse events were observed. All drug-related treatment-emergent adverse events showed no clear dose-related trends. Following an intravenous infusion of QX006N at doses that ranged from 0.3 mg/kg to 10 mg/kg, the half-life increased from 24.7 to 208 hours in a dose-dependent manner, while clearance decreased from 0.0828 to 0.0065 L/h. The maximum concentration exhibited nearly dose-proportional increases, and the area under the curve displayed a more than dose-proportional increment with non-linear pharmacokinetic characteristics. The incidence of anti-drug antibodies was observed to increase over time for doses that ranged from 1.0 mg/kg to 10.0 mg/kg of QX006N, reaching its peak at day 57 (range 62.50-87.50%). Conversely, the incidence of anti-drug antibodies in the QX006N 0.3-mg/kg and placebo cohorts remained low.

Conclusions: QX006N demonstrated acceptable safety, tolerability, and pharmacokinetic characteristics in healthy subjects when administered as a single intravenous infusion at doses that ranged from 0.3 mg/kg to 10.0 mg/kg. Based on the pharmacokinetic and safety outcomes, a recommended effective dose of 300 mg is proposed for future phase Ib studies.

Clinical trial registration: This study has been registered at http://www.chinadrugtrials.org.cn/ under identifier CTR20212834.