Congenital Antithrombin Deficiency
Conditions
Brief summary
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.
Interventions
DRUGAtenativ
Antithrombin concentrate
Sponsors
Octapharma
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Thrombotic event incidence | Up to day 30 post treatment initiation | The primary objective of this study is to assess the incidence of the composite of TEs and TEEs in patients with congenital antithrombin deficiency under cover of Atenativ for surgical procedures or parturition |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Single dose Pharmacokinetics of Atenativ: Maximum plasma concentration (Cmax) | Before first infusion, 20 minutes, 1 hour, 3 hours, 8 hrs, 1 day, 2 days, 3, days, 4 days, 5 days, 6 days, 7 days, 8 days, 10 days, 12 days and 14 days post-infusion | Assess the maximum plasma concentration (Cmax) after a single dose of Atenativ in patients with congenital antithrombin deficiency |
| Single dose Pharmacokinetics of Atenativ: Half-life (t1/2) | Before first infusion, 20 minutes, 1 hour, 3 hours, 8 hrs, 1 day, 2 days, 3, days, 4 days, 5 days, 6 days, 7 days, 8 days, 10 days, 12 days and 14 days post-infusion | Assess the half-life (t1/2) after a single dose of Atenativ in patients with congenital antithrombin deficiency |
| Single dose Pharmacokinetics of Atenativ: Mean residence time (MRT) | Before first infusion, 20 minutes, 1 hour, 3 hours, 8 hrs, 1 day, 2 days, 3, days, 4 days, 5 days, 6 days, 7 days, 8 days, 10 days, 12 days and 14 days post-infusion | Assess the mean residence time (MRT) after a single dose of Atenativ in patients with congenital antithrombin deficiency |
| Single dose Pharmacokinetics of Atenativ: Clearance (CL) | Before first infusion, 20 minutes, 1 hour, 3 hours, 8 hrs, 1 day, 2 days, 3, days, 4 days, 5 days, 6 days, 7 days, 8 days, 10 days, 12 days and 14 days post-infusion | Assess the clearance (CL) after a single dose of Atenativ in patients with congenital antithrombin deficiency |
| Single dose Pharmacokinetics of Atenativ: Incremental in vivo recovery (IVR) | Before first infusion, 20 minutes, 1 hour, 3 hours, 8 hrs, 1 day, 2 days, 3, days, 4 days, 5 days, 6 days, 7 days, 8 days, 10 days, 12 days and 14 days post-infusion | Assess the Incremental in vivo recovery after a single dose of Atenativ in patients with congenital antithrombin deficiency |
| Single dose Pharmacokinetics of Atenativ: Volume of distribution at steady state (Vss) | Before first infusion, 20 minutes, 1 hour, 3 hours, 8 hrs, 1 day, 2 days, 3, days, 4 days, 5 days, 6 days, 7 days, 8 days, 10 days, 12 days and 14 days post-infusion | Assess the volume of distribution at steady state (Vss) after a single dose of Atenativ in patients with congenital antithrombin deficiency |
| Single dose Pharmacokinetics of Atenativ: Area under the curve (AUCnorm(0-∞)) | Up to day 14 post PK infusion | Assess the area under the curve (AUCnorm(0-∞)) of Atenativ in patients with congenital antithrombin deficiency |
| 10. Coagulation parameters: Activated partial thromboplastin time [aPTT] | Up to day 7 post treatment initiation | Assess activated partial thromboplastin time \[aPTT\] in patients with congenital antithrombin deficiency undergoing surgical procedures or parturition |
| Coagulation parameters: Prothrombin time [PT] | Up to day 7 post treatment initiation | Assess prothrombin time \[PT\] in patients with congenital antithrombin deficiency undergoing surgical procedures or parturition |
| Coagulation parameters: International normalised ratio [INR] | Up to day 7 post treatment initiation | Assess international normalised ratio \[INR\] in patients with congenital antithrombin deficiency undergoing surgical procedures or parturition |
| Coagulation parameters: Fibrinogen level | Up to day 7 post treatment initiation | Assess fibrinogen in patients with congenital antithrombin deficiency undergoing surgical procedures or parturition |
| Safety and tolerability: Number of adverse events (AEs) | Up to day 30 post treatment initiation | Number of adverse events (AEs) following treatment with Atenativ in patients with congenital antithrombin deficiency |
| Single dose Pharmacokinetics of Atenativ: Maximum Plasma Concentration (Tmax) | Before first infusion, 20 minutes, 1 hour, 3 hours, 8 hrs, 1 day, 2 days, 3, days, 4 days, 5 days, 6 days, 7 days, 8 days, 10 days, 12 days and 14 days post-infusion | Assess the time to reach Maximum Plasma Concentration (Tmax) after a single dose of Atenativ in patients with congenital antithrombin deficiency |
Countries
Armenia, Austria, Czechia, France, Georgia, Germany, Hungary, Israel, Italy, Romania, Serbia, Spain, United Kingdom, United States
Contacts
Primary ContactSigurd Knaub
Outcome results
None listed