PB0238 - 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 is a rare genetic disorder associated with spontaneous thrombotic events (TEs) and thromboembolic events (TEEs) that occur in connection with surgery and childbirth. Antithrombin replacement therapy can be used for prevention of TEs/TEEs in these settings.

Aims: Study ATN-106 will evaluate the efficacy, safety, and pharmacokinetics (PK) of a high-purity, double virus inactivated, lyophilized human antithrombin III concentrate (Octapharma AB) in surgery and childbirth.

Methods: ATN-106 (NCT04918173) is a multicenter, prospective, open-label, Phase 3 study in adult (≥18–≤80 years) and adolescent (12–16 years) patients with congenital antithrombin deficiency (plasma antithrombin ≤60%), and personal/family history of TEs/TEEs. The study will enroll 34 patients, including ≥18 non-pregnant patients for the PK phase and ~20 patients who are a) non-pregnant and scheduled to undergo an elective surgical procedure known to be associated with a high risk for occurrence of TEs or TEEs, or b) pregnant and scheduled for caesarean section or delivery. Patients will provide informed consent prior to treatment. The study was approved by relevant medical ethics committees.

For PK analysis, patients will receive a single 60 IU/kg intravenous (IV) infusion of antithrombin concentrate. For efficacy and safety analyses, a single dose targeting antithrombin level 120% of normal will be administered prior to surgery/delivery, followed by maintenance doses every 24 hours, as described in Figure 1.

The primary outcome is the composite incidence of TEs and TEEs; secondary outcomes are described in Table 2.

Results: To date, two patients have been enrolled, in the US. Study completion is expected in Q3 2024.

Conclusion(s): The results from this pivotal registration study are expected to strengthen the available evidence indicating that human plasma-derived antithrombin concentrate effectively prevents thrombotic and thromboembolic events in patients with congenital antithrombin deficiency in surgery and delivery settings and has a favorable safety profile.