QX008N, a humanized IgG1 monoclonal antibody against thymic stromal lymphopoietin (TSLP) with Fc engineering to extend half-life, was developed with the aim of exploring whether its extended half-life and cost-effective production could potentially address unmet needs in severe asthma therapy, such as the need for less frequent dosing and improved accessibility. This first-in-human, phase I trial evaluated pharmacokinetics (PK), tolerability, and immunogenicity of QX008N in healthy Chinese subjects following subcutaneous (SC) and intravenous (IV) administration. SC group dosing demonstrated dose-proportional exposure; for the 280 mg and 560 mg SC doses, AUC₀-∞ values were 37,611 and 81,450 h·μg/mL, respectively, with delayed Tmax (5-8 days) and absolute bioavailability of 62%-67%. Following SC administration, Cmax values were 30.0 μg/mL (280 mg) and 63.9 μg/mL (560 mg), whereas IV administration produced a Cmax of 225.83 μg/mL at 2 h. QX008N exhibited a prolonged half-life (median 30.4 days (range 25.0-47.1) for the 560 mg SC dose), surpassing tezepelumab's 26 days, supporting potential every 6-8 week dosing. All pharmacokinetic parameters, including terminal elimination half-life (t½), were derived from plasma concentration-time data. Tolerability profiles were favorable: all adverse events were mild/moderate (e.g., self-resolving rash). No injection-site reactions were observed following single-dose administration in healthy subjects. Immunogenicity was low (5.6% ADA incidence; no neutralizing antibodies), with no PK or tolerability impact. Overall, QX008N demonstrated predictable pharmacokinetics, low immunogenicity, and a tolerability profile consistent with single-dose administration of monoclonal antibodies in healthy subjects. These findings provide foundational PK and tolerability data to support subsequent clinical evaluation in patients.
Shen et al. (Sun,) studied this question.