Methods: This phase 1b multi-center, double-blind study randomized subjects with Type 1 or 2 HAE to receive 2 subcutaneous doses of DX-2930 on Days 1 and 15 in dose groups of 30, 100, 300 or 400 mg (n=4, 4, 5, 11) or placebo (n=13). Blood samples were obtained prior to and following study drug administration (Days 1, 8, 22, 64, 92, 120). The ability of DX-2930 to inhibit pKal in FXIIa-activated citrated plasma was assessed using Western blot for 2-chain HMWK.
Results: In FXIIa-activated samples mean 2-chain HMWK levels were significantly reduced and essentially normalized in the 300 and 400 mg dose groups on Days 8 and 22, and on Days 8, 22 and 50, respectively, when compared to placebo-treated subjects. Treatment with 300 or 400 mg DX-2930 also attenuated 2-chain generation to levels at or below that observed in healthy individuals. Levels of 2-chain HMWK did not differ from pre-dose plasma samples in samples collected on Days 64, 92 or 120 following DX-2930, which correspond to periods of low drug exposure.
Conclusions: DX-2930 inhibits pKal in a dose and time-dependent manner in HAE patients.