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

Phase 3
Recruiting
Conditions
Congenital antithrombin deficiency
Registration Number
2024-515830-34-00
Lead Sponsor
Octapharma AG
Brief Summary

The primary objective of this study is to assess the incidence of the composite of Thrombotic Events (TEs) and Thromboembolic Event (TEEs) in patients with congenital antithrombin deficiency under cover of Atenativ for surgical procedures or parturition.

Detailed Description

Not available

Recruitment & Eligibility

Status
Ongoing, recruiting
Sex
Not specified
Target Recruitment
22
Inclusion Criteria

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

Documented congenital antithrombin deficiency, defined by plasma level of antithrombin ≤60%

Personal or family history of TEs or TEEs

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

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

Patient has provided informed consent

Exclusion Criteria

Requires emergency surgery or emergency caesarean section

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

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

Refusal to receive transfusion of blood-derived products

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

Persons dependent on the sponsor, the investigator or the center of investigation

Persons placed in an institution by administrative or judicial order

Prior diagnosis of heparin-induced thrombocytopenia

TE or TEE within the last 6 months

Female patients who are nursing at the time of screening

Have participated in another investigational study within the last 30 days

Has undergone surgery within the last 6 weeks

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)

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

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

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
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 post treatment initiation.

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 post treatment initiation.

Secondary Outcome Measures
NameTimeMethod
• PK parameters: o Area under the curve (AUCnorm(0–∞)) o Maximum plasma concentration (Cmax) o Half-life (t1/2) o Mean residence time (MRT) o Clearance (CL) o Incremental in vivo recovery (IVR; peak concentration of antithrombin observed within the first hour after infusion) o Volume of distribution at steady state (Vss) o Time to reach Maximum Plasma Concentration (Tmax)

• PK parameters: o Area under the curve (AUCnorm(0–∞)) o Maximum plasma concentration (Cmax) o Half-life (t1/2) o Mean residence time (MRT) o Clearance (CL) o Incremental in vivo recovery (IVR; peak concentration of antithrombin observed within the first hour after infusion) o Volume of distribution at steady state (Vss) o Time to reach Maximum Plasma Concentration (Tmax)

• Efficacy Parameters: o Antithrombin activity; o Coagulation parameters (activated partial thromboplastin time [aPTT], prothrombin time [PT], international normalised ratio [INR] and fibrinogen)

• Efficacy Parameters: o Antithrombin activity; o Coagulation parameters (activated partial thromboplastin time [aPTT], prothrombin time [PT], international normalised ratio [INR] and fibrinogen)

• Safety Parameters: o Adverse events (AEs) and serious AEs (SAEs); o Length of hospital stay; o Vital signs (including systolic and diastolic blood pressure, pulse rate, body temperature, respiration rate, results of physical examination); o Standard haematological and clinical chemistry safety variables, as well as thrombogenicity markers including D-dimer, prothrombin fragment 1 + 2 (F1+2)*, and thrombin-antithrombin complex (TAT)* * if available from local laboratories

• Safety Parameters: o Adverse events (AEs) and serious AEs (SAEs); o Length of hospital stay; o Vital signs (including systolic and diastolic blood pressure, pulse rate, body temperature, respiration rate, results of physical examination); o Standard haematological and clinical chemistry safety variables, as well as thrombogenicity markers including D-dimer, prothrombin fragment 1 + 2 (F1+2)*, and thrombin-antithrombin complex (TAT)* * if available from local laboratories

Trial Locations

Locations (17)

University Of Debrecen

🇭🇺

Debrecen, Hungary

Universitaetsklinikum Bonn AöR

🇩🇪

Bonn, Germany

Gerinnungszentrum Rhein-Ruhr Aerztepartnerschaft Dr. med. Hannelore Rott Fachaerztin fuer Transfusionsmedizin Haemostaseologie Dr. med. Susan Halimeh Fachaerztin fuer Transfusionsmedizin Haemostaseologie Dr. med. Guenther Kappert Facharzt fuer Laboratoriumsmedizin Haemostaseologie

🇩🇪

Duisburg, Germany

Sana Kliniken Duisburg GmbH

🇩🇪

Duisburg, Germany

Vivantes Netzwerk fuer Gesundheit GmbH

🇩🇪

Berlin, Germany

Hospital Universitario La Paz

🇪🇸

Madrid, Spain

Complejo Hospitalario Universitario De Ourense

🇪🇸

Ourense, Spain

Hospital Universitario Central De Asturias

🇪🇸

Oviedo, Spain

Centro Emofilia E Trombosi Angelo Bianchi Bonomi

🇮🇹

Milan, Italy

Azienda Ospedaliera di Padova

🇮🇹

Padova, Italy

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University Of Debrecen
🇭🇺Debrecen, Hungary
Zsolt Csaba Olah
Site contact
+36308397806
zsolah@med.unideb.hu

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