Clinical Study to Investigate the PK, Efficacy, and Safety of Wilate in Patients With Severe Hemophilia A
21 de diciembre de 2020 actualizado por: Octapharma
Clinical Study to Investigate the Pharmacokinetics, Efficacy, Safety, and Immunogenicity of Wilate in Previously Treated Patients With Severe Hemophilia A
The purpose of this study is to obtain additional data on the safety and efficacy of Wilate in PTPs with hemophilia A with at least 150 previous exposure days (EDs) to a FVIII concentrate who undergo prophylactic treatment with Wilate for 6 months and at least 50 EDs, thus supplementing the existing database to obtain approval of Wilate for the indication hemophilia A in the USA.
Descripción general del estudio
Tipo de estudio
Intervencionista
Inscripción (Actual)
57
Fase
- Fase 3
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
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Sofia, Bulgaria
- Specialized Hospital for Active Treatment "Joan Pavel"
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Barnaul, Federación Rusa
- Barnaul Branch of RAMS hematology center
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Moscow, Federación Rusa
- Federal Scientific Hematology Center
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Budapest, Hungría
- National Haemophilia Centre
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Krakow, Polonia
- Krakowskie Centrum Medyczne
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Rzeszow, Polonia
- Korczowski Bartosz Gabinet Lekarski
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Bucharest, Rumania
- Centrul Medical Unirea -Policlinica Enescu
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
12 años y mayores (Niño, Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Masculino
Descripción
Inclusion Criteria:
- Severe hemophilia A (<1% FVIII:C) according to medical history
- Male patients aged ≥12 years
- Previous treatment with a FVIII concentrate for at least 150 exposure days (EDs)
- Immunocompetence (CD4+ count >200/µL)
- Good documentation of the historical bleeding rate (at least for the 6 months preceding study start)
- Voluntarily given, fully informed written and signed consent obtained by the patient (or parent/legal guardian in case of adolescents) before any study-related procedures are conducted
Whenever possible, the interval between the Screening Visit and the PK or Non-PK Visit should not exceed 30 days. If the 30-day interval is exceeded, determination of the CD4+ count is to be repeated and must be >200/µL for patients to be enrolled (i.e., exclusion criterion no. 4).
Exclusion Criteria:
- Any coagulation disorders other than hemophilia A
- History of FVIII inhibitor activity (≥0.6 BU) or detectable FVIII inhibitory anti-bodies (≥0.6 BU using the Nijmegen modification of the Bethesda assay) at screening, as determined by the central laboratory
- Severe liver or kidney diseases (alanine aminotransferase [ALAT] and aspartate transaminase [ASAT] levels >5 times of upper limit of normal, creatinine>120 µmol/L)
- Patients receiving or scheduled to receive immunomodulating drugs (other than anti-retroviral chemotherapy) such as alpha-interferon, prednisone (equivalent to >10 mg/day), or similar drugs
- Treatment with any investigational medicinal product in another interventional clinical study currently or within 4 weeks before enrollment
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- 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: All patients
All patients will receive Wilate for prophylactic treatment
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Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Total Annualized Bleeding Rate (TABR)
Periodo de tiempo: 6 months
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The total number of bleeding events (BEs) was documented by patients in a patient diary (together with the investigator in case of on-site treatments), which was reviewed at each follow-up visit by site personnel.
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6 months
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Spontaneous Annualized Bleeding Rate (SABR)
Periodo de tiempo: 6 months
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The number of spontaneous bleeding events (BEs) was documented by patients in a patient diary (together with the investigator in case of on-site treatments), which was reviewed at each follow-up visit by site personnel.
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6 months
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Efficacy of Wilate in the Treatment of Breakthrough BEs
Periodo de tiempo: 6 months
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The proportion of BEs successfully treated with Wilate were documented by the patient (together with the investigator in case of on-site treatments) in the patient diary for all BEs according to a 4-point hemostatic efficacy scale including the four items: 'excellent,' 'good,' moderate,' and 'none', where 'excellent' was defined as "Abrupt pain relief and/or unequivocal improvement in objective signs of bleeding within approximately 8 hours after a single injection" (best outcome) and 'none' was defined as "No improvement within 12 hours, or worsening of symptoms, requiring more than two injections for complete resolution" (worst outcome).
All efficacy ratings assessed as either 'excellent' or 'good' were considered 'successfully treated.'
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6 months
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Wilate Consumption Data (Average Total Normdose of FVIII IU/kg Per Month of Study) for Prophylaxis
Periodo de tiempo: 6 months
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The average consumption of Wilate per month of study (IU/kg) for all patients receiving prophylaxis.
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6 months
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Pharmacokinetic (PK) Assessment (Area Under the Curve [AUC] Norm) of FVIII:C
Periodo de tiempo: Initial PK visit (Day -1) and PK study completion visit (6 months); data collected 1 h prior to injection and 15 min, 1 h, 3 h, 6 h, 9 h, 24 h, 30 h and 48 h after the end of injection
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PK assessments of FVIII:C were conducted using the one-stage (OS) assay.
The value of the AUCnorm of FVIII:C was calculated based on the FVIII:C values measured in the patients participating in the PK study.
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Initial PK visit (Day -1) and PK study completion visit (6 months); data collected 1 h prior to injection and 15 min, 1 h, 3 h, 6 h, 9 h, 24 h, 30 h and 48 h after the end of injection
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Pharmacokinetic (PK) Assessment (in Vivo Half-Life (t1/2)) of FVIII:C
Periodo de tiempo: Initial PK assessment (Day -1) and PK study completion visit (6 months); data collected 1 h prior to infusion and 15 min, 1 h, 3 h, 6 h, 9 h, 24 h, 30 h and 48 h after the end of injection
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PK assessments of FVIII:C were conducted using the one-stage (OS) assay.
The in vivo half-life of FVIII:C was calculated based on the FVIII:C values measured in the patients participating in the PK study.
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Initial PK assessment (Day -1) and PK study completion visit (6 months); data collected 1 h prior to infusion and 15 min, 1 h, 3 h, 6 h, 9 h, 24 h, 30 h and 48 h after the end of injection
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Pharmacokinetic (PK) Assessment (Maximum Plasma Concentration [Cmax]) of FVIII:C
Periodo de tiempo: Initial PK assessment (Day -1) and 6 months
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PK assessments of FVIII:C were conducted using the one-stage (OS) assay.
The maximum plasma concentration of FVIII:C was calculated based on the FVIII:C values measured in the patients participating in the PK study.
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Initial PK assessment (Day -1) and 6 months
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Incremental in Vivo Recovery (IVR) of Wilate Over Time
Periodo de tiempo: Baseline, 3 and 6 months
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The rise in FVIII activity in IU/dl per unit dose administered in IU/kg was determined from all patients at baseline, 3 and 6 months, using the OS assay.
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Baseline, 3 and 6 months
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Association Between ABO Blood Type and the FVIII:C Half-life of Wilate (OS Assay)
Periodo de tiempo: 6 months
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Analysis of variance (ANOVA) was used in an exploratory sense to assess an association between ABO blood type and the FVIII:C half-life of Wilate.
This was analyzed by calculating the mean square in a one-stage assay.
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6 months
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Association Between VWF:Ag Concentration and the FVIII:C Half-life of Wilate
Periodo de tiempo: 6 months
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ANOVA was used in an exploratory sense to assess an association between VWF:Ag with the FVIII:C half-life of Wilate.
This was analyzed by calculating the mean square in a one-stage assay.
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6 months
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Safety and Tolerability of Wilate by Monitoring Adverse Events (AEs) Throughout the Study
Periodo de tiempo: 6 months
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At each (scheduled or unscheduled) study visit, AEs were documented by the investigator throughout the study.
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6 months
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Immunogenicity of Wilate by Testing for FVIII Inhibitors
Periodo de tiempo: 6 months
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FVIII inhibitor activity was determined at each study visit before the injection of Wilate using the modified Bethesda assay (Nijmegen modification).
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6 months
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Virus Safety Measured by the Number of Parvovirus B19 Seroconversions Between Baseline (BL) and End of Study
Periodo de tiempo: 6 months
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Virus safety was evaluated by taking a plasma sample for parvovirus B19 antibody testing before the first injection of Wilate.
All patients negative at screening were tested again at the study completion visit.
The number with Parvovirus B19 seroconversions between BL and end of study was recorded.
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6 months
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Otras medidas de resultado
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Efficacy of Wilate in Surgical Prophylaxis
Periodo de tiempo: 6 months
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Hemostatic efficacy was assessed at the end of surgery by the surgeon and at end of the postoperative period by the hematologist, using a 4-point hemostatic efficacy scale including the four items: 'excellent' (best possible outcome), 'good', 'moderate' and 'none' (worst outcome).
Overall efficacy was assessed by the investigator, taking both the intra and postoperative assessments into account, and using the 'excellent,' 'good,' moderate,' and 'none' scale.
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6 months
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Actual)
1 de diciembre de 2016
Finalización primaria (Actual)
29 de marzo de 2018
Finalización del estudio (Actual)
29 de marzo de 2018
Fechas de registro del estudio
Enviado por primera vez
27 de octubre de 2016
Primero enviado que cumplió con los criterios de control de calidad
1 de noviembre de 2016
Publicado por primera vez (Estimar)
3 de noviembre de 2016
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
19 de enero de 2021
Última actualización enviada que cumplió con los criterios de control de calidad
21 de diciembre de 2020
Última verificación
1 de diciembre de 2020
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- WIL-27
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
NO
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Sí
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
No
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