Eficacia de Atenativ en pacientes con deficiencia congénita de antitrombina sometidas a cirugía o parto
Estudio de fase 3, multicéntrico, prospectivo, abierto, no controlado para evaluar la eficacia, la seguridad y la farmacocinética de Atenativ en pacientes con deficiencia congénita de antitrombina sometidos a cirugía o parto
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.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 3
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Sigurd Knaub
- Número de teléfono: +41554512141
- Correo electrónico: Sigurd.Knaub@octapharma.com
Ubicaciones de estudio
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Berlin, Alemania
- Reclutamiento
- Vivantes Klinikum Friedrichshain Klinik für Angiologie Hämostaseologie
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Bonn, Alemania
- Reclutamiento
- UKB Bonn Institut für Experimentelle Hämatologie und Transfusionsmedizin
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Duisburg, Alemania
- Reclutamiento
- Gerinnungszentrum Rhein-Ruhr
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Yerevan, Armenia
- Reclutamiento
- Yeolyan Hematology and Oncology Centre
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Vienna, Austria
- Reclutamiento
- Medizinische Universität Wien. Universitätsklinik für Innere Medizin Klinische Abteilung für Hämatologie und Hämostaseologie
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Nymburk, Chequia
- Reclutamiento
- Centre for Thrombosis and Haemaostasis Nemocnice
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Madrid, España, 28046
- Reclutamiento
- Hospital Universitario La Paz
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Murcia, España
- Reclutamiento
- Hospital Universitario Morales Meseguer
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Ourense, España, 32005
- Reclutamiento
- Ourense University Hospital
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Principality of Asturias
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Oviedo, Principality of Asturias, España, 33011
- Reclutamiento
- Central University Hospital of Asturias
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District of Columbia
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Washington D.C., District of Columbia, Estados Unidos, 20057
- Reclutamiento
- Georgetown University Hospital
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Florida
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Miami, Florida, Estados Unidos, 33124
- Reclutamiento
- University of Miami, Miller School of Medicine
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Illinois
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Peoria, Illinois, Estados Unidos, 61615
- Reclutamiento
- Bleeding and Clotting Disorders Institute
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New York
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New York, New York, Estados Unidos, 10065
- Reclutamiento
- Weill Cornell Medicine, New York Presbyterian Hospital
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North Carolina
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Durham, North Carolina, Estados Unidos, 27708
- Reclutamiento
- Duke University School of Medicine, Division of Hematology
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Bron, Francia
- Reclutamiento
- Centre de Référence de l'Hémophilie Unité d'Hémostase Clinique Hôpital Cardiologique Louis Pradel
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Reims, Francia
- Reclutamiento
- University Hospital of Reims
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Rouen, Francia
- Reclutamiento
- Centre Hospitalier Universitaire de Rouen (CHU de Rouen) - Centre de Traitement des Maladies Hemorragiques (CRTH) (Centre d'Hemophiles)
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Tbilisi, Georgia
- Reclutamiento
- Aversi Clinic
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Debrecen, Hungría
- Reclutamiento
- University of Debrecen, Medical and Health Science Centre
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Petah Tikva, Israel
- Reclutamiento
- Rabin Medical Centre, Institute of Haematology
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Ramat Gan, Israel
- Reclutamiento
- Sheba Medical Centre
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Bergamo, Italia, 24127
- Reclutamiento
- Unita Strutturale Complessa di Immunoematologia e Medicina Trasfusionale -Dipartimento Interaziendale di Medicina Trasfusionale ed Ematologia - ASST Papa Giovanni XXIII ematologia Piazza OMS, 1
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Milan, Italia
- Reclutamiento
- Universita degli Studi di Milano - IRCCS Ospedale Maggiore Policlinico - Centro Emofilia e Trombosi Angelo Bianchi Bonomi
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Padua, Italia
- Reclutamiento
- University of Padua Medical School
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Roma, Italia
- Reclutamiento
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS
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London, Reino Unido
- Reclutamiento
- Royal-free Hospital-Katherine Dormandy Haemophilia and Thrombosis Centre
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London, Reino Unido
- Reclutamiento
- St. Thomas Hospital, Guy's and St. Thomas' NHS Foundation Trust
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Craiova, Rumania
- Reclutamiento
- Emergency County Hospital Craiova
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Belgrade, Serbia
- Reclutamiento
- Clinical Center of Serbia
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
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 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
Exclusion Criteria:
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Requires emergency surgery or emergency caesarean section
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Has undergone surgery within the last 6 weeks
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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)
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Malignancies, renal failure (patients on renal replacement therapy), or severe liver disease (aspartate aminotransferase [ASAT] >5 times the upper limit of normal)
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Body mass index >40 kg/m2 (for non-pregnant patients, only)
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Known hypersensitivity or allergic reaction to antithrombin or any of the excipients in Atenativ
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History of anaphylactic reaction(s) to blood or blood components
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Refusal to receive transfusion of blood-derived products
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Administration of any antithrombin concentrate or antithrombin-containing blood product within 14 days of either of the two phases of the study
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Prior diagnosis of heparin-induced thrombocytopenia
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TE or TEE within the last 6 months
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Female patients who are nursing at the time of screening*
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Have participated in another investigational study within the last 30 days
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Persons dependent on the sponsor, the investigator or the centre of investigation
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Persons placed in an institution by administrative or judicial order
- criterion does not include female patients who plan to breastfeed after giving birth
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Prevención
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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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 |
Antithrombin concentrate |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Thrombotic event incidence
Periodo de tiempo: Up to day 30 post treatment initiation
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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
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Single dose Pharmacokinetics of Atenativ: Area under the curve (AUCnorm(0-∞))
Periodo de tiempo: Up to day 14 post PK infusion
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Assess the area under the curve (AUCnorm(0-∞)) of Atenativ in patients with congenital antithrombin deficiency |
Up to day 14 post PK infusion
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Single dose Pharmacokinetics of Atenativ: Maximum plasma concentration (Cmax)
Periodo de tiempo: 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
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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
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Single dose Pharmacokinetics of Atenativ: Half-life (t1/2)
Periodo de tiempo: 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
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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
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Single dose Pharmacokinetics of Atenativ: Mean residence time (MRT)
Periodo de tiempo: 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
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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
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Single dose Pharmacokinetics of Atenativ: Clearance (CL)
Periodo de tiempo: 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
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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
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Single dose Pharmacokinetics of Atenativ: Incremental in vivo recovery (IVR)
Periodo de tiempo: 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
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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
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Single dose Pharmacokinetics of Atenativ: Volume of distribution at steady state (Vss)
Periodo de tiempo: 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
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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
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Single dose Pharmacokinetics of Atenativ: Maximum Plasma Concentration (Tmax)
Periodo de tiempo: 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
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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
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10. Coagulation parameters: Activated partial thromboplastin time [aPTT]
Periodo de tiempo: Up to day 7 post treatment initiation
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Assess activated partial thromboplastin time [aPTT] in patients with congenital antithrombin deficiency undergoing surgical procedures or parturition |
Up to day 7 post treatment initiation
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Coagulation parameters: Prothrombin time [PT]
Periodo de tiempo: Up to day 7 post treatment initiation
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Assess prothrombin time [PT] in patients with congenital antithrombin deficiency undergoing surgical procedures or parturition |
Up to day 7 post treatment initiation
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Coagulation parameters: International normalised ratio [INR]
Periodo de tiempo: Up to day 7 post treatment initiation
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Assess international normalised ratio [INR] in patients with congenital antithrombin deficiency undergoing surgical procedures or parturition |
Up to day 7 post treatment initiation
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Coagulation parameters: Fibrinogen level
Periodo de tiempo: Up to day 7 post treatment initiation
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Assess fibrinogen in patients with congenital antithrombin deficiency undergoing surgical procedures or parturition |
Up to day 7 post treatment initiation
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Safety and tolerability: Number of adverse events (AEs)
Periodo de tiempo: Up to day 30 post treatment initiation
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Number of adverse events (AEs) following treatment with Atenativ in patients with congenital antithrombin deficiency |
Up to day 30 post treatment initiation
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Colaboradores e Investigadores
Patrocinador
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- ATN-106
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
producto fabricado y exportado desde los EE. UU.
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