PB0716 - Prospective, Phase III Study of the Efficacy, Safety, and Pharmacokinetics of a Human Antithrombin III Concentrate in Congenital Antithrombin Deficiency During Surgery or Childbirth

Background: Congenital antithrombin deficiency (CAD) is a rare genetic blood disorder associated with spontaneous thrombotic events (TEs) and thromboembolic events (TEEs) in connection with surgery and childbirth. Human plasma-derived or recombinant antithrombin replacement therapy can be used for the prevention of TEs/TEEs in these settings.

Aims: To evaluate the efficacy, safety, and pharmacokinetics (PK) of a high-purity, double virus inactivated, lyophilized human antithrombin III concentrate (Atenativ®) in patients with CAD undergoing surgery or delivery.

Methods: The ATN-106 study (NCT04918173, Sponsor: Octapharma) is a multicenter, prospective, single-group, open-label, Phase III study in male and female patients (12–80 years) with documented CAD (plasma antithrombin ≤60%), and personal or family history of TEs or TEEs. For the PK phase, ~14 non-pregnant adult and 4 adolescent patients will receive one 60 IU/kg intravenous (IV) infusion of antithrombin concentrate. The treatment phase will enrol ~20 patients who are either non-pregnant and scheduled to undergo elective surgery associated with high risk of TEs or TEEs, or pregnant and scheduled for caesarean section or delivery. A single IV dose targeting an antithrombin level of 120% of normal will be administered prior to surgery/delivery followed by maintenance doses every 24 hours for ~2–7 (surgical patients) or ~5 (delivery patients) days targeting an antithrombin level of 80–120% of normal (Figure 1).
The primary outcome measure will be the incidence of composite TEs and TEEs with secondary outcome measures including PK measurements, safety and tolerability (number of adverse events).

Results: Enrollment is estimated to start in Q1 2022 and end in Q3 2024.

Conclusion(s): The results from this pivotal registration study are expected to confirm and strengthen available evidence indicating that human plasma-derived antithrombin concentrate is effective in preventing TEs and TEEs in patients with CAD in surgery and delivery, with a favorable safety profile.