Clinical trial NCT04918173: Efficacy of Atenativ in Patients With Congenital Antithrombin Deficiency Undergoing Surgery or Delivery
Official title: A Multicenter, 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Congenital Antithrombin Deficiency
Lead sponsor: Octapharma
Sponsor class: INDUSTRY
First posted: 2021-06-08
Enrollment: 38
Sex: ALL
Minimum age (years): 12
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.


Eligibility criteria: 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

Primary outcomes:
measure: Thrombotic event incidence
timeFrame: Up to day 30 post treatment initiation
Secondary outcomes:
measure: Single dose Pharmacokinetics of Atenativ: Area under the curve (AUCnorm(0-∞))
timeFrame: Up to day 14 post PK infusion
measure: Single dose Pharmacokinetics of Atenativ: Maximum plasma concentration (Cmax)
timeFrame: 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
measure: Single dose Pharmacokinetics of Atenativ: Half-life (t1/2)
timeFrame: 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
measure: Single dose Pharmacokinetics of Atenativ: Mean residence time (MRT)
timeFrame: 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
measure: Single dose Pharmacokinetics of Atenativ: Clearance (CL)
timeFrame: 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
measure: Single dose Pharmacokinetics of Atenativ: Incremental in vivo recovery (IVR)
timeFrame: 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
measure: Single dose Pharmacokinetics of Atenativ: Volume of distribution at steady state (Vss)
timeFrame: 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
measure: Single dose Pharmacokinetics of Atenativ: Maximum Plasma Concentration (Tmax)
timeFrame: 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
measure: 10. Coagulation parameters: Activated partial thromboplastin time [aPTT]
timeFrame: Up to day 7 post treatment initiation
measure: Coagulation parameters: Prothrombin time [PT]
timeFrame: Up to day 7 post treatment initiation
measure: Coagulation parameters: International normalised ratio [INR]
timeFrame: Up to day 7 post treatment initiation
measure: Coagulation parameters: Fibrinogen level
timeFrame: Up to day 7 post treatment initiation
measure: Safety and tolerability: Number of adverse events (AEs)
timeFrame: Up to day 30 post treatment initiation
Other outcomes:
Locations:
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Peoria
country: United States
facility: Bleeding and Clotting Disorders Institute
state: Illinois
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Vienna
country: Austria
facility: Universitätsklinik für Innere Medizin Klinische Abteilung für Hämatologie und Hämostaseologie
city: Nymburk
country: Czechia
facility: Centre for Thrombosis and Haemaostasis
city: Bron
country: France
facility: Centre de Référence de l'Hémophilie Unité d'Hémostase Clinique Hôpital Cardiologique Louis Pradel
city: Reims
country: France
facility: University Hospital of Reims
city: Rouen
country: France
facility: Centre Hospitalier Universitaire de Rouen (CHU de Rouen) - Centre de Traitement des Maladies Hemorragiques (CRTH) (Centre d'Hemophiles)
city: Tbilisi
country: Georgia
facility: Aversi Clinic
city: Berlin
country: Germany
facility: Klinik fur Angiologie Hamostaseologie Haus 12 A Gerinnungssprechstunde
city: Bonn
country: Germany
facility: UKB Bonn Institut für Experimentelle Hämatologie und Transfusionsmedizin
city: Duisburg
country: Germany
facility: Gerinnungszentrum Rhein-Ruhr
city: Debrecen
country: Hungary
facility: University of Debrecen, Medical and Health Science Centre
city: Petach Tikva
country: Israel
facility: Rabin Medical Centre, Institute of Haematology
city: Ramat Gan
country: Israel
facility: Sheba Medical Centre
city: Bergamo
country: Italy
facility: Unita Strutturale Complessa di Immunoematologia e Medicina Trasfusionale -Dipartimento Interaziendale di Medicina Trasfusionale ed Ematologia - ASST Papa Giovanni XXIII ematologia Piazza OMS, 1
city: Milan
country: Italy
facility: Universita degli Studi di Milano - IRCCS Ospedale Maggiore Policlinico - Centro Emofilia e Trombosi Angelo Bianchi Bonomi
city: Padua
country: Italy
facility: University of Padua Medical School
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia
city: Oviedo
country: Spain
facility: Central University Hospital of Asturias
state: Asturias
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Ourense
country: Spain
facility: Ourense University Hospital
city: London
country: United Kingdom
facility: Royal-free Hospital-Katherine Dormandy Haemophilia and Thrombosis Centre
city: London
country: United Kingdom
facility: St. Thomas Hospital
Study officials:
References: