Efficacy of Atenativ in Patients With Congenital Antithrombin Deficiency Undergoing Surgery or Delivery

A Multicenter, Prospective, Open-label, Uncontrolled Phase 3 Study to Assess the Efficacy, Safety and Pharmacokinetics of Atenativ in Patients With Congenital Antithrombin Deficiency Undergoing Surgery or Delivery

The goal of this study is to assess the incidence of the composite of thrombotic events (TEs) and thromboembolic events (TEEs) in patients with congenital antithrombin deficiency under when they receive Atenativ for surgical procedures or parturition.

Inclusion Criteria:

1. Adult male or female patients ≥18 and ≤80 years of age. Solely in the US, 4 male or female patients between ≥12 and <17 years of age will be enrolled into the PK phase, and subsequently in the treatment phase, if applicable
2. Documented congenital antithrombin deficiency, defined by plasma activity level of antithrombin ≤60% from medical history
3. Personal or family history of TEs or TEEs (except for PK patients)
4. For the Treatment Phase: either a) non-pregnant surgical patients scheduled for elective surgical procedure(s) known to be associated with a high risk for occurrence of TEs or TEEs, or b) pregnant patients of at least 27 weeks gestational age who are scheduled for caesarean section or delivery
5. For female patients of childbearing potential entering the PK Phase who are not known to be pregnant, and for female surgical patients of childbearing potential entering the Treatment Phase for any procedure other than caesarean section or delivery, a negative urine pregnancy test at screening and at baseline
6. Patient has provided informed consent

Exclusion Criteria:

1. Requires emergency surgery or emergency caesarean section

2. Has undergone surgery within the last 6 weeks

3. History or suspicion of another hereditary thrombophilic disorder other than antithrombin deficiency (e.g., activated protein C [APC] resistance/Factor V Leiden, Protein S or C deficiency, prothrombin gene mutation [G20210A], or acquired [lupus anticoagulant] thrombophilic disorder)

4. Malignancies, renal failure (patients on renal replacement therapy), or severe liver disease (aspartate aminotransferase [ASAT] >5 times the upper limit of normal)

5. Body mass index >40 kg/m2 (for non-pregnant patients, only)

6. Known hypersensitivity or allergic reaction to antithrombin or any of the excipients in Atenativ

7. History of anaphylactic reaction(s) to blood or blood components

8. Refusal to receive transfusion of blood-derived products

9. Administration of any antithrombin concentrate or antithrombin-containing blood product within 14 days of either of the two phases of the study

10. Prior diagnosis of heparin-induced thrombocytopenia

11. TE or TEE within the last 6 months

12. Female patients who are nursing at the time of screening*

13. Have participated in another investigational study within the last 30 days

14. Persons dependent on the sponsor, the investigator or the centre of investigation

15. Persons placed in an institution by administrative or judicial order

    • criterion does not include female patients who plan to breastfeed after giving birth