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

NCT04918173 | Recruiting Phase 3 FDA Drug

• 1 other identifier: ATN-106
• Study Type: interventional
• Target: 38
• Locations: 14 countries
• Sites: 30

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.

Conditions

Congenital Antithrombin Deficiency

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (13)

• Single dose Pharmacokinetics of Atenativ: Area under the curve (AUCnorm(0-∞))

  Up to day 14 post PK infusion

• 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

• 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

• 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

• 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

Study Arms (1)

Atenativ treatment

EXPERIMENTAL

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

Interventions

Atenativ DRUG

Antithrombin concentrate

Atenativ treatment

Eligibility Criteria

• Age: 12 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Documented congenital antithrombin deficiency, defined by plasma activity level of antithrombin ≤60% from medical history
• Personal or family history of TEs or TEEs (except for PK patients)
• 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

You may not qualify if:

• Requires emergency surgery or emergency caesarean section
• 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 (patients 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)
• 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 within 14 days of either of the two phases of the study
• 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
• Persons dependent on the sponsor, the investigator or the centre of investigation
• Persons placed in an institution by administrative or judicial order

Sponsors & Collaborators

• Octapharma: lead

Study Sites (30)

Georgetown University

Washington D.C., District of Columbia, 20057, United States

RECRUITING

University of Miami

Miami, Florida, 33124, United States

RECRUITING

Bleeding and Clotting Disorders Institute

Peoria, Illinois, 61615, United States

RECRUITING

Weill Cornell Medicine

New York, New York, 10065, United States

RECRUITING

Duke University

Durham, North Carolina, 27708, United States

RECRUITING

Yeolyan Hematology and Oncology Centre

Yerevan, Armenia

NOT YET RECRUITING

Universitätsklinik für Innere Medizin Klinische Abteilung für Hämatologie und Hämostaseologie

Vienna, Austria

RECRUITING

Centre for Thrombosis and Haemaostasis

Nymburk, Czechia

RECRUITING

Centre de Référence de l'Hémophilie Unité d'Hémostase Clinique Hôpital Cardiologique Louis Pradel

Bron, France

RECRUITING

University Hospital of Reims

Reims, France

RECRUITING

Centre Hospitalier Universitaire de Rouen (CHU de Rouen) - Centre de Traitement des Maladies Hemorragiques (CRTH) (Centre d'Hemophiles)

Rouen, France

RECRUITING

Aversi Clinic

Tbilisi, Georgia

RECRUITING

Klinik fur Angiologie Hamostaseologie Haus 12 A Gerinnungssprechstunde

Berlin, Germany

RECRUITING

UKB Bonn Institut für Experimentelle Hämatologie und Transfusionsmedizin

Bonn, Germany

RECRUITING

Gerinnungszentrum Rhein-Ruhr

Duisburg, Germany

RECRUITING

University of Debrecen, Medical and Health Science Centre

Debrecen, Hungary

RECRUITING

Rabin Medical Centre, Institute of Haematology

Petah Tikva, Israel

RECRUITING

Sheba Medical Centre

Ramat Gan, Israel

RECRUITING

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

Bergamo, 24127, Italy

RECRUITING

Universita degli Studi di Milano - IRCCS Ospedale Maggiore Policlinico - Centro Emofilia e Trombosi Angelo Bianchi Bonomi

Milan, Italy

RECRUITING

University of Padua Medical School

Padua, Italy

RECRUITING

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, Italy

RECRUITING

Emergency County Hospital Craiova

Craiova, Romania

RECRUITING

Clinical Center of Serbia

Belgrade, Serbia

RECRUITING

Central University Hospital of Asturias

Oviedo, Principality of Asturias, 33011, Spain

RECRUITING

Hospital Universitario La Paz

Madrid, 28046, Spain

RECRUITING

Hospital Universitario Morales Meseguer

Murcia, Spain

RECRUITING

Ourense University Hospital

Ourense, 32005, Spain

RECRUITING

Royal-free Hospital-Katherine Dormandy Haemophilia and Thrombosis Centre

London, United Kingdom

RECRUITING

St. Thomas Hospital

London, United Kingdom

RECRUITING

MeSH Terms

Interventions

Antithrombin III

Intervention Hierarchy (Ancestors)

Antithrombin Proteins; Serpins; Peptides; Amino Acids, Peptides, and Proteins; Alpha-Globulins; Serum Globulins; Blood Proteins; Proteins; Globulins; Blood Coagulation Factor Inhibitors; Biological Factors

Central Study Contacts

Sigurd Knaub

CONTACT

+41554512141; Sigurd.Knaub@octapharma.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 18, 2021
• First Posted: June 8, 2021
• Study Start: July 1, 2022
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: November 21, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

AR (1); RO (1); SE (1); ES (4); GB (2); DE (3); GE (1); US (5); CZ (1); IL (2); FR (3); IT (4); HU (1); AU (1)