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

Phase 3

Recruiting

• Conditions: Congenital Antithrombin Deficiency
• Interventions: Drug: Atenativ

• Registration Number: NCT04918173
• Lead Sponsor: Octapharma

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-05-18
• Study First Submitted QC: 2021-06-04
• Study First Posted: 2021-06-08
• Study Start: 2022-07-01
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-31
• Last Update Posted: 2025-02-04
• Primary Completion: 2025-12-01
• Study Completion: 2025-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 38

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 the treatment phase, if needed
2. Level of antithrombin ≤60%
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

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, 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 other than the study medication 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
13. Have participated in another investigational study within the last 30 days

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Atenativ treatment	Atenativ	Patients will receive a single intravenous infusion of Atenativ for PK analysis. Patients will receive a single intravenous dose followed by maintenance doses administered every 24 hours for approximately 2-7 days for surgical patients and approximately 5 days for parturients

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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: 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
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: 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
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
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: 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: 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
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

Trial Locations

Locations (23)

Georgetown University; 🇺🇸 Washington, District of Columbia, United States

University of Miami; 🇺🇸 Miami, Florida, United States

Bleeding and Clotting Disorders Institute; 🇺🇸 Peoria, Illinois, United States

Universitätsklinik für Innere Medizin Klinische Abteilung für Hämatologie und Hämostaseologie; 🇦🇹 Vienna, Austria

Centre de Référence de l'Hémophilie Unité d'Hémostase Clinique Hôpital Cardiologique Louis Pradel; 🇫🇷 Bron, France

University Hospital of Reims; 🇫🇷 Reims, France

Centre Hospitalier Universitaire de Rouen (CHU de Rouen) - Centre de Traitement des Maladies Hemorragiques (CRTH) (Centre d'Hemophiles); 🇫🇷 Rouen, France

Klinik fur Angiologie Hamostaseologie Haus 12 A Gerinnungssprechstunde; 🇩🇪 Berlin, Germany

UKB Bonn Institut für Experimentelle Hämatologie und Transfusionsmedizin; 🇩🇪 Bonn, Germany

Gerinnungszentrum Rhein-Ruhr; 🇩🇪 Duisburg, Germany

University of Debrecen, Medical and Health Science Centre; 🇭🇺 Debrecen, Hungary

Rabin Medical Centre, Institute of Haematology; 🇮🇱 Petach Tikva, Israel

Sheba Medical Centre; 🇮🇱 Ramat Gan, Israel

Unita Strutturale Complessa di Immunoematologia e Medicina Trasfusionale -Dipartimento Interaziendale di Medicina Trasfusionale ed Ematologia - ASST Papa Giovanni XXIII ematologia Piazza OMS, 1; 🇮🇹 Bergamo, Italy

Universita degli Studi di Milano - IRCCS Ospedale Maggiore Policlinico - Centro Emofilia e Trombosi Angelo Bianchi Bonomi; 🇮🇹 Milan, Italy

University of Padua Medical School; 🇮🇹 Padua, Italy

Fondazione Policlinico Universitario Agostino Gemelli IRCCS; 🇮🇹 Roma, Italy

Clinical Center of Serbia; 🇷🇸 Belgrade, Serbia

Central University Hospital of Asturias; 🇪🇸 Oviedo, Asturias, Spain

Hospital Universitario La Paz; 🇪🇸 Madrid, Spain

Ourense University Hospital; 🇪🇸 Ourense, Spain

Royal-free Hospital-Katherine Dormandy Haemophilia and Thrombosis Centre; 🇬🇧 London, United Kingdom

St. Thomas Hospital; 🇬🇧 London, United Kingdom