Congenital antithrombin deficiency MedDRA version: 23.0 Level: LLT Classification code 10083881 Term: Antithrombin deficiency System Organ Class: 100000004850
Conditions
Interventions
Trade Name: Atenativ
Product Name: Atenativ
Product Code: N/A
Pharmaceutical Form: Powder and solvent for solution for infusion
INN or Proposed INN: N/A
Other descriptive name: HUMAN PLASMA DERIVED AN
Sponsors
Octapharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients who meet all of the following criteria are eligible for the study: 1. Adult male or female patients =18 and =80 years of age 2. Documented congenital antithrombin deficiency, defined by plasma level of antithrombin =60% [16] 3. Personal or family history of TEs or TEEs 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
Exclusion criteria: Patients who meet any of the following criteria at the time of screening are not eligible for the study: 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, or severe liver disease (aspartate aminotransferase [ASAT] >5 times the upper limit of normal) 5. Body mass index >40 kg/m2 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 other than the study medication within 14 days of either of the two phases of the study 10. Prior diagnosis with heparin-induced thrombocytopenia 11. TE or TEE within the last 6 months 12. Female patients who are nursing 13. Have participated in another investigational study within the last 30 days
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective 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 cover of Atenativ for surgical procedures or parturition;Secondary Objective: The secondary objectives of this study are to: • Assess the single-dose PK of Atenativ in patients with congenital antithrombin deficiency • Assess coagulation parameters in patients with congenital antithrombin deficiency undergoing surgical procedures or parturition • Assess the safety and tolerability of Atenativ in patients with congenital antithrombin deficiency;Primary end point(s): The primary endpoint is the incidence of the composite of TEs and TEEs in patients with congenital antithrombin deficiency under cover of Atenativ for surgical procedures or parturition to 30 days after treatment initiation;Timepoint(s) of evaluation of this end point: 30 days after treatment initiation | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints include the following PK parameters following a single dose of Atenativ: • Area under the curve (AUCnorm(0–8)) • Maximum plasma concentration (Cmax) • Half-life (t1/2) • Mean residence time (MRT) • Clearance (CL) • Incremental IVR (peak concentration of antithrombin observed within the first hour after infusion) • Volume of distribution at steady state (Vss) • Time to reach maximum plasma concentration (Tmax) Efficacy • Antithrombin activity • Coagulation parameters (activated partial thromboplastin time [aPTT], prothrombin time [PT], international normalised ratio [INR] and fibrinogen) Safety • AEs and serious AEs (SAEs) • Length of hospital stay • Vital signs (including systolic and diastolic blood pressure, pulse rate, body temperature, respiration rate, results of physical examination) • Standard haematological and clinical chemical safety variables, as well as thrombogenicity markers including D-dimer, prothrombin fragment 1 + 2 (F1+2), and thrombin-antithrombin complex (TAT).;Timepoint(s) of evaluation of this end point: occurrence of TEs and TEEs | — |
Countries
Austria, Belgium, Canada, France, Germany, Hungary, Italy, Spain, United Kingdom, United States
Contacts
Public ContactCristina Solomon
Octapharma AG
Outcome results
None listed