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

Congenital Antithrombin Deficiency Clinical Trial

Official title:

A Multicentre, 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04918173
• Other study ID #: ATN-106
• Status: Recruiting
• Phase: Phase 3
• Start date: July 1, 2022
• Est. completion date: June 1, 2025

Study information

• Verified date: April 2024
• Source: Octapharma
• Contact: Sigurd Knaub
• Phone: +41554512141
• Email: Sigurd.Knaub[@]octapharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 38
• Est. completion date: June 1, 2025
• Est. primary completion date: June 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Antithrombin III Deficiency
• Congenital Antithrombin Deficiency

Intervention

Drug:
• Atenativ
Antithrombin concentrate

Locations

Country	Name	City	State
Austria	Universitätsklinik für Innere Medizin Klinische Abteilung für Hämatologie und Hämostaseologie	Vienna
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
Germany	Klinik fur Angiologie Hamostaseologie Haus 12 A Gerinnungssprechstunde	Berlin
Germany	Gerinnungszentrum Rhein-Ruhr	Duisburg
Hungary	University of Debrecen, Medical and Health Science Centre	Debrecen
Israel	Rabin Medical Centre, Institute of Haematology	Petach Tikva
Israel	Sheba Medical Centre	Ramat Gan
Italy	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
Serbia	Clinical Center of Serbia	Belgrade
Spain	Hospital Universitario La Paz	Madrid
Spain	Ourense University Hospital	Ourense
Spain	Central University Hospital of Asturias	Oviedo	Asturias
United Kingdom	Royal-free Hospital-Katherine Dormandy Haemophilia and Thrombosis Centre	London
United Kingdom	St. Thomas Hospital	London
United States	University of Miami	Miami	Florida
United States	Bleeding and Clotting Disorders Institute	Peoria	Illinois
United States	Georgetown University	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Octapharma

Countries where clinical trial is conducted

United States,  Austria,  France,  Germany,  Hungary,  Israel,  Italy,  Serbia,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Thrombotic event incidence	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	Up to day 30 post treatment initiation
Secondary	Single dose Pharmacokinetics of Atenativ: Area under the curve (AUCnorm(0-8))	Assess the area under the curve (AUCnorm(0-8)) of Atenativ in patients with congenital antithrombin deficiency	Up to day 14 post PK infusion
Secondary	Single dose Pharmacokinetics of Atenativ: Maximum plasma concentration (Cmax)	Assess the maximum plasma concentration (Cmax) after a single dose of Atenativ in patients with congenital antithrombin deficiency	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
Secondary	Single dose Pharmacokinetics of Atenativ: Half-life (t1/2)	Assess the half-life (t1/2) after a single dose of Atenativ in patients with congenital antithrombin deficiency	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
Secondary	Single dose Pharmacokinetics of Atenativ: Mean residence time (MRT)	Assess the mean residence time (MRT) after a single dose of Atenativ in patients with congenital antithrombin deficiency	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
Secondary	Single dose Pharmacokinetics of Atenativ: Clearance (CL)	Assess the clearance (CL) after a single dose of Atenativ in patients with congenital antithrombin deficiency	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
Secondary	Single dose Pharmacokinetics of Atenativ: Incremental in vivo recovery (IVR)	Assess the Incremental in vivo recovery after a single dose of Atenativ in patients with congenital antithrombin deficiency	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
Secondary	Single dose Pharmacokinetics of Atenativ: Volume of distribution at steady state (Vss)	Assess the volume of distribution at steady state (Vss) after a single dose of Atenativ in patients with congenital antithrombin deficiency	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
Secondary	Single dose Pharmacokinetics of Atenativ: Maximum Plasma Concentration (Tmax)	Assess the time to reach Maximum Plasma Concentration (Tmax) after a single dose of Atenativ in patients with congenital antithrombin deficiency	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
Secondary	10. Coagulation parameters: Activated partial thromboplastin time [aPTT]	Assess activated partial thromboplastin time [aPTT] in patients with congenital antithrombin deficiency undergoing surgical procedures or parturition	Up to day 7 post treatment initiation
Secondary	Coagulation parameters: Prothrombin time [PT]	Assess prothrombin time [PT] in patients with congenital antithrombin deficiency undergoing surgical procedures or parturition	Up to day 7 post treatment initiation
Secondary	Coagulation parameters: International normalised ratio [INR]	Assess international normalised ratio [INR] in patients with congenital antithrombin deficiency undergoing surgical procedures or parturition	Up to day 7 post treatment initiation
Secondary	Coagulation parameters: Fibrinogen level	Assess fibrinogen in patients with congenital antithrombin deficiency undergoing surgical procedures or parturition	Up to day 7 post treatment initiation
Secondary	Safety and tolerability: Number of adverse events (AEs)	Number of adverse events (AEs) following treatment with Atenativ in patients with congenital antithrombin deficiency	Up to day 30 post treatment initiation