PB1320 - A Phase 1 Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MG1113 in Healthy Subjects and Hemophilia Patients

Background: MG1113 is a human monoclonal IgG4 antibody with high affinity for tissue factor pathway inhibitor (TFPI), which inhibits the binding of TFPI and activated factor X (FXa) and induces the activation of FX.

Aims: A first-in-human phase 1 study was conducted to investigate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of MG1113 in healthy subjects and hemophilia patients (NCT03855696).

Methods: A randomized, double-blind, placebo-controlled, ascending dose phase 1 study of MG1113 was conducted. The study was reviewed and approved by the institutional review board and written informed consent was obtained. A single ascending dose of 0.5, 1.7, or 3.3 mg/kg subcutaneously (SC) or 3.3 mg/kg intravenously (IV) was administered to healthy volunteers (N=8) and a single dose of 1.7 or 3.3 mg/kg was administered subcutaneously to hemophilia (N = 9).

Results: A dose-dependent systemic exposure of MG1113 in the SC group was observed in both healthy and hemophilia participants. After MG1113 treatment, free TFPI and FXa (residual TFPI) activity were decreased and both diluted PT and lag time (TGA) were shortened. However, peak height (TGA), ETP (endogenous thrombin potential, TGA), D-dimer, and prothrombin fragment 1+2 increased compared to the baseline. The most frequent adverse drug reaction (ADR) in healthy volunteers was venous thrombosis (N=5, three mild and two moderate grade). In hemophilia patients, muscle twitching and pain in extremity (N=1) was initially reported as suspected unexpected serious adverse reactions (SUSARs), however, it was finally considered not related with MG1113. Two healthy volunteers (one in the placebo group and one in MG1113 group) exhibited a positive anti-drug antibody (ADA) test after treatment.

Conclusion(s): MG1113 had a favorable safety profile and was well tolerated in healthy subjects and hemophilia patients receiving a single dose up to 3.3 mg/kg (SC). MG1113 also exhibited a desirable PK profile showing a dose-dependent systemic exposure. (Previously submitted at ICKSH2023)