Subcutaneous MG1113 in severe hemophilia A and B: phase 1b study for safety, pharmacokinetics, and pharmacodynamics

MG1113 is an immunoglobulin G4 monoclonal antibody targeting the Kunitz-2 domain of tissue factor pathway inhibitor (TFPI), developed as a hemostatic rebalancing agent for patients with hemophilia A or B.

We aimed to investigate the safety, pharmacokinetics (PK), pharmacodynamics, and preliminary hemostatic effects of MG1113.

This phase 1b clinical trial was conducted in a multicenter, prospective, stepwise dose-escalating (2.0, 3.0, and 3.3 mg/kg) design. MG1113 was administered subcutaneously once weekly for 8 weeks.

Fifteen male patients (n = 5/cohort) diagnosed with severe hemophilia A (n = 14) or B (n = 1) without inhibitors were enrolled. MG1113 was well tolerated, with an adverse event (AE) rate of 40.0% (6/15). No serious AEs, early withdrawals, or dose interruptions occurred. PK analysis demonstrated a nonlinear profile, with the peak plasma concentration at 33 to 48 hours post dose. Free TFPI and diluted prothrombin time (PT) decreased from baseline, while thrombin generation markers increased. Exploratory analysis showed a notable numerical reduction in annualized total bleeding rates at higher doses: 91.7% at 3.0 mg/kg and 76.2% at 3.3 mg/kg. The zero bleeding rate was 20.0%, 60.0%, and 40.0% at doses of 2.0, 3.0, and 3.3 mg/kg, respectively.

MG1113, administered subcutaneously as a prophylaxis in patients with severe hemophilia A or B without inhibitors for 8 weeks, demonstrated an acceptable safety profile with a PK profile suitable for once-a-week dosing. The pharmacodynamics marker changes were consistent with TFPI inhibition, which was associated with reductions in bleeding events.

This trial was prospectively registered at www.ClinicalTrials.gov (#NCT05493631).