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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Congenital Antithrombin Deficiency
• Intervention / Treatment: Drug: Atenativ

• Study Type: Interventional
• Enrollment (Estimated): 38
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Sigurd Knaub; Phone Number: +41554512141; Email: Sigurd.Knaub@octapharma.com

Study Locations

• Armenia
  • Yerevan, Armenia
    • Recruiting
    • Yeolyan Hematology and Oncology Centre
• Austria
  • Vienna, Austria
    • Recruiting
    • Universitätsklinik für Innere Medizin Klinische Abteilung für Hämatologie und Hämostaseologie
• Czechia
  • Nymburk, Czechia
    • Recruiting
    • Centre for Thrombosis and Haemaostasis
• France
  • Bron, France
    • Recruiting
    • Centre de Référence de l'Hémophilie Unité d'Hémostase Clinique Hôpital Cardiologique Louis Pradel
  • Reims, France
    • Recruiting
    • University Hospital of Reims
  • Rouen, France
    • Recruiting
    • Centre Hospitalier Universitaire de Rouen (CHU de Rouen) - Centre de Traitement des Maladies Hemorragiques (CRTH) (Centre d'Hemophiles)
• Georgia
  • Tbilisi, Georgia
    • Recruiting
    • Aversi Clinic
• Germany
  • Berlin, Germany
    • Recruiting
    • Klinik fur Angiologie Hamostaseologie Haus 12 A Gerinnungssprechstunde
  • Bonn, Germany
    • Recruiting
    • UKB Bonn Institut für Experimentelle Hämatologie und Transfusionsmedizin
  • Duisburg, Germany
    • Recruiting
    • Gerinnungszentrum Rhein-Ruhr
• Hungary
  • Debrecen, Hungary
    • Recruiting
    • University of Debrecen, Medical and Health Science Centre
• Israel
  • Petah Tikva, Israel
    • Recruiting
    • Rabin Medical Centre, Institute of Haematology
  • Ramat Gan, Israel
    • Recruiting
    • Sheba Medical Centre
• Italy
  • Bergamo, Italy, 24127
    • Recruiting
    • Unita Strutturale Complessa di Immunoematologia e Medicina Trasfusionale -Dipartimento Interaziendale di Medicina Trasfusionale ed Ematologia - ASST Papa Giovanni XXIII ematologia Piazza OMS, 1
  • Milan, Italy
    • Recruiting
    • Universita degli Studi di Milano - IRCCS Ospedale Maggiore Policlinico - Centro Emofilia e Trombosi Angelo Bianchi Bonomi
  • Padua, Italy
    • Recruiting
    • University of Padua Medical School
  • Roma, Italy
    • Recruiting
    • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Romania
  • Craiova, Romania
    • Recruiting
    • Emergency County Hospital Craiova
• Serbia
  • Belgrade, Serbia
    • Recruiting
    • Clinical Center of Serbia
• Spain
  • Madrid, Spain, 28046
    • Recruiting
    • Hospital Universitario La Paz
  • Murcia, Spain
    • Recruiting
    • Hospital Universitario Morales Meseguer
  • Ourense, Spain, 32005
    • Recruiting
    • Ourense University Hospital
  • Principality of Asturias
    • Oviedo, Principality of Asturias, Spain, 33011
      • Recruiting
      • Central University Hospital of Asturias
• United Kingdom
  • London, United Kingdom
    • Recruiting
    • St. Thomas Hospital
  • London, United Kingdom
    • Recruiting
    • Royal-free Hospital-Katherine Dormandy Haemophilia and Thrombosis Centre
• United States
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20057
      • Recruiting
      • Georgetown University
  • Florida
    • Miami, Florida, United States, 33124
      • Recruiting
      • University of Miami
  • Illinois
    • Peoria, Illinois, United States, 61615
      • Recruiting
      • Bleeding and Clotting Disorders Institute
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Weill Cornell Medicine
  • North Carolina
    • Durham, North Carolina, United States, 27708
      • Recruiting
      • Duke University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 80 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atenativ treatment; During the PK phase, patients will receive a 60 IU/kg Atenativ as a single intravenous infusion for PK analysis. During the treatment phase, patients will receive a single intravenous loading dose followed by maintenance doses administered every 24 hours for approximately 2-7 days for surgical patients and approximately 5 days for parturients	Drug: Atenativ; Antithrombin concentrate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Single dose Pharmacokinetics of Atenativ: Area under the curve (AUCnorm(0-∞))	Assess the area under the curve (AUCnorm(0-∞)) of Atenativ in patients with congenital antithrombin deficiency	Up to day 14 post PK infusion
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
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
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
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
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
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
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
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
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
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
Coagulation parameters: Fibrinogen level	Assess fibrinogen in patients with congenital antithrombin deficiency undergoing surgical procedures or parturition	Up to day 7 post treatment initiation
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

Collaborators and Investigators

• Sponsor: Octapharma

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: May 18, 2021
• First Submitted That Met QC Criteria: June 4, 2021
• First Posted (Actual): June 8, 2021

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: June 2, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Blood Coagulation Disorders; Blood Protein Disorders; Blood Coagulation Disorders, Inherited; Thrombophilia; Antithrombin III Deficiency; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Blood Proteins; Serum Globulins; Globulins; Antithrombin Proteins; Serpins; Alpha-Globulins; Blood Coagulation Factor Inhibitors; Antithrombin III
• Other Study ID Numbers: ATN-106

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No