Back to resultsEfficacy of Atenativ in Patients With Congenital Antithrombin Deficiency Undergoing Surgery or Delivery
Primary Purpose
Congenital Antithrombin Deficiency
Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Atenativ
Sponsored by
About this trial
This is an interventional prevention trial for Congenital Antithrombin Deficiency
Eligibility Criteria
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
- 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
- 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, 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 other than the study medication 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
- Have participated in another investigational study within the last 30 days
Sites / Locations
- Georgetown UniversityRecruiting
- University of Miami
- Rush University Medical Center
- Bleeding and Clotting Disorders InstituteRecruiting
- Universitätsklinik für Innere Medizin Klinische Abteilung für Hämatologie und HämostaseologieRecruiting
- University Hospital of ReimsRecruiting
- Centre Hospitalier Universitaire de Rouen (CHU de Rouen) - Centre de Traitement des Maladies Hemorragiques (CRTH) (Centre d'Hemophiles)Recruiting
- Klinik fur Angiologie Hamostaseologie Haus 12 A GerinnungssprechstundeRecruiting
- Gerinnungszentrum Rhein-RuhrRecruiting
- University of Debrecen, Medical and Health Science CentreRecruiting
- Unita Strutturale Complessa di Immunoematologia e Medicina Trasfusionale -Dipartimento Interaziendale di Medicina Trasfusionale ed Ematologia - ASST Papa Giovanni XXIII ematologia Piazza OMS, 1Recruiting
- Universita degli Studi di Milano - IRCCS Ospedale Maggiore Policlinico - Centro Emofilia e Trombosi Angelo Bianchi BonomiRecruiting
- University of Padua Medical SchoolRecruiting
- Fondazione Policlinico Universitario Agostino Gemelli IRCCSRecruiting
- Central University Hospital of AsturiasRecruiting
- Hospital Universitario La PazRecruiting
- Ourense University HospitalRecruiting
- St. Thomas HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Atenativ treatment
Arm Description
Patients will receive a single intravenous infusion of Atenativ for PK analysis. Patients will receive a single intravenous dose followed by maintenance doses administered every 24 hours for approximately 2-7 days for surgical patients and approximately 5 days for parturients
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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
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
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
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
Single dose Pharmacokinetics of Atenativ: Clearance (CL)
Assess the clearance (CL) after a single dose of Atenativ in patients with congenital antithrombin deficiency
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
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
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
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
Coagulation parameters: Prothrombin time [PT]
Assess prothrombin time [PT] in patients with congenital antithrombin deficiency undergoing surgical procedures or parturition
Coagulation parameters: International normalised ratio [INR]
Assess international normalised ratio [INR] in patients with congenital antithrombin deficiency undergoing surgical procedures or parturition
Coagulation parameters: Fibrinogen level
Assess fibrinogen in patients with congenital antithrombin deficiency undergoing surgical procedures or parturition
Safety and tolerability: Number of adverse events (AEs)
Number of adverse events (AEs) following treatment with Atenativ in patients with congenital antithrombin deficiency
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04918173
Brief Title
Efficacy of Atenativ in Patients With Congenital Antithrombin Deficiency Undergoing Surgery or Delivery
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 1, 2022 (Actual)
Primary Completion Date
December 1, 2024 (Anticipated)
Study Completion Date
December 1, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Octapharma
4. Oversight
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
5. Study Description
Brief 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Congenital Antithrombin Deficiency
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
38 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Atenativ treatment
Arm Type
Experimental
Arm Description
Patients will receive a single intravenous infusion of Atenativ for PK analysis. Patients will receive a single intravenous dose followed by maintenance doses administered every 24 hours for approximately 2-7 days for surgical patients and approximately 5 days for parturients
Intervention Type
Drug
Intervention Name(s)
Atenativ
Intervention Description
Antithrombin concentrate
Primary Outcome Measure Information:
Title
Thrombotic event incidence
Description
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
Time Frame
Up to day 30 post treatment initiation
Secondary Outcome Measure Information:
Title
Single dose Pharmacokinetics of Atenativ: Area under the curve (AUCnorm(0-∞))
Description
Assess the area under the curve (AUCnorm(0-∞)) of Atenativ in patients with congenital antithrombin deficiency
Time Frame
Up to day 14 post PK infusion
Title
Single dose Pharmacokinetics of Atenativ: Maximum plasma concentration (Cmax)
Description
Assess the maximum plasma concentration (Cmax) after a single dose of Atenativ in patients with congenital antithrombin deficiency
Time Frame
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
Title
Single dose Pharmacokinetics of Atenativ: Half-life (t1/2)
Description
Assess the half-life (t1/2) after a single dose of Atenativ in patients with congenital antithrombin deficiency
Time Frame
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
Title
Single dose Pharmacokinetics of Atenativ: Mean residence time (MRT)
Description
Assess the mean residence time (MRT) after a single dose of Atenativ in patients with congenital antithrombin deficiency
Time Frame
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
Title
Single dose Pharmacokinetics of Atenativ: Clearance (CL)
Description
Assess the clearance (CL) after a single dose of Atenativ in patients with congenital antithrombin deficiency
Time Frame
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
Title
Single dose Pharmacokinetics of Atenativ: Incremental in vivo recovery (IVR)
Description
Assess the Incremental in vivo recovery after a single dose of Atenativ in patients with congenital antithrombin deficiency
Time Frame
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
Title
Single dose Pharmacokinetics of Atenativ: Volume of distribution at steady state (Vss)
Description
Assess the volume of distribution at steady state (Vss) after a single dose of Atenativ in patients with congenital antithrombin deficiency
Time Frame
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
Title
Single dose Pharmacokinetics of Atenativ: Maximum Plasma Concentration (Tmax)
Description
Assess the time to reach Maximum Plasma Concentration (Tmax) after a single dose of Atenativ in patients with congenital antithrombin deficiency
Time Frame
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
Title
10. Coagulation parameters: Activated partial thromboplastin time [aPTT]
Description
Assess activated partial thromboplastin time [aPTT] in patients with congenital antithrombin deficiency undergoing surgical procedures or parturition
Time Frame
Up to day 7 post treatment initiation
Title
Coagulation parameters: Prothrombin time [PT]
Description
Assess prothrombin time [PT] in patients with congenital antithrombin deficiency undergoing surgical procedures or parturition
Time Frame
Up to day 7 post treatment initiation
Title
Coagulation parameters: International normalised ratio [INR]
Description
Assess international normalised ratio [INR] in patients with congenital antithrombin deficiency undergoing surgical procedures or parturition
Time Frame
Up to day 7 post treatment initiation
Title
Coagulation parameters: Fibrinogen level
Description
Assess fibrinogen in patients with congenital antithrombin deficiency undergoing surgical procedures or parturition
Time Frame
Up to day 7 post treatment initiation
Title
Safety and tolerability: Number of adverse events (AEs)
Description
Number of adverse events (AEs) following treatment with Atenativ in patients with congenital antithrombin deficiency
Time Frame
Up to day 30 post treatment initiation
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
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
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, 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 other than the study medication 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
Have participated in another investigational study within the last 30 days
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sigurd Knaub
Phone
+41554512141
Email
Sigurd.Knaub@octapharma.com
Facility Information:
Facility Name
Georgetown University
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20057
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33124
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Bleeding and Clotting Disorders Institute
City
Peoria
State/Province
Illinois
ZIP/Postal Code
61615
Country
United States
Individual Site Status
Recruiting
Facility Name
Universitätsklinik für Innere Medizin Klinische Abteilung für Hämatologie und Hämostaseologie
City
Vienna
Country
Austria
Individual Site Status
Recruiting
Facility Name
University Hospital of Reims
City
Reims
Country
France
Individual Site Status
Recruiting
Facility Name
Centre Hospitalier Universitaire de Rouen (CHU de Rouen) - Centre de Traitement des Maladies Hemorragiques (CRTH) (Centre d'Hemophiles)
City
Rouen
Country
France
Individual Site Status
Recruiting
Facility Name
Klinik fur Angiologie Hamostaseologie Haus 12 A Gerinnungssprechstunde
City
Berlin
Country
Germany
Individual Site Status
Recruiting
Facility Name
Gerinnungszentrum Rhein-Ruhr
City
Duisburg
Country
Germany
Individual Site Status
Recruiting
Facility Name
University of Debrecen, Medical and Health Science Centre
City
Debrecen
Country
Hungary
Individual Site Status
Recruiting
Facility Name
Unita Strutturale Complessa di Immunoematologia e Medicina Trasfusionale -Dipartimento Interaziendale di Medicina Trasfusionale ed Ematologia - ASST Papa Giovanni XXIII ematologia Piazza OMS, 1
City
Bergamo
ZIP/Postal Code
24127
Country
Italy
Individual Site Status
Recruiting
Facility Name
Universita degli Studi di Milano - IRCCS Ospedale Maggiore Policlinico - Centro Emofilia e Trombosi Angelo Bianchi Bonomi
City
Milan
Country
Italy
Individual Site Status
Recruiting
Facility Name
University of Padua Medical School
City
Padua
Country
Italy
Individual Site Status
Recruiting
Facility Name
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
City
Roma
Country
Italy
Individual Site Status
Recruiting
Facility Name
Central University Hospital of Asturias
City
Oviedo
State/Province
Asturias
ZIP/Postal Code
33011
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital Universitario La Paz
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Individual Site Status
Recruiting
Facility Name
Ourense University Hospital
City
Ourense
ZIP/Postal Code
32005
Country
Spain
Individual Site Status
Recruiting
Facility Name
St. Thomas Hospital
City
London
Country
United Kingdom
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Efficacy of Atenativ in Patients With Congenital Antithrombin Deficiency Undergoing Surgery or Delivery
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