Phase Ib/II Study of Preliminary Efficacy, Safety and Pharmacodynamics of MG-K10, a Humanised Monoclonal Antibody Targeting IL-4Rα, in Adult Chinese Patients With Asthma.

BACKGROUND

MG-K10 is a long-acting, humanised monoclonal antibody against interleukin-4 receptor alpha (IL-4Rα), which inhibits IL-4 and IL-13-mediated signalling to reduce type 2 inflammation in asthma.

OBJECTIVE

This Phase Ib/II study aimed to evaluate the preliminary efficacy, safety and pharmacodynamic characteristics of MG-K10 in Chinese patients with asthma.

METHODS

This study included an initial phase Ib to evaluate safety and tolerability, followed by a phase II study in which eligible patients with moderate-to-severe asthma were randomised 1:1:1 to receive MG-K10 300 mg every 2 weeks (Q2W), MG-K10 300 mg every 4 weeks (Q4W), or a matched placebo (2 mL) Q2W subcutaneously for 24 weeks. The primary endpoint was the absolute change from baseline in the prebronchodilator forced expiratory volume in 1 s (FEV1) at week 12. Secondary efficacy endpoints, including asthma control, the rate of severe exacerbations and safety, were assessed. This trial is registered with ClinicalTrials.gov (NCT05382910).

RESULTS

A total of 64, 60 and 63 patients were randomised to the MG-K10 Q2W, MG-K10 Q4W and placebo groups respectively. At week 12, the least squares mean improvements in prebronchodilator FEV1 were significantly greater in both MG-K10 groups than in the placebo group [Q2W vs. placebo: 0.35 L (95% CI, 0.208-0.490), Q4W vs. placebo: 0.30 L (95% CI, 0.156 to 0.441), both p < 0.0001]. Greater FEV1 improvements were observed in patients with baseline blood eosinophils ≥ 0.3 × 109/L. The incidence of adverse events was similar across groups [MG-K10 300 mg, Q2W (79.7%), MG-K10 300 mg Q4W (85.0%) and placebo groups (79.4%)]. MG-K10 was safe and well-tolerated, and consistent with the known safety signals.

CONCLUSIONS

MG-K10 was superior to placebo in improving lung function, enhancing asthma control and reducing severe exacerbations in patients with asthma. The once-every-4-week regimen offers extended dosing intervals that may enhance medication adherence.