Clinical Trials Register

Summary
EudraCT Number:	2014-000742-30
Sponsor's Protocol Code Number:	261202
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2014-06-09
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2014-000742-30

A.3

Full title of the trial

A phase 3 prospective, uncontrolled, multicenter study evaluating pharmacokinetics, efficacy, safety, and immunogenicity of BAX 855 (PEGylated full-length Recombinant FVIII) in previously treated pediatric patients with severe hemophilia A

ESTUDIO DE FASE 3, PROSPECTIVO, NO CONTROLADO Y MULTICÉNTRICO QUE EVALÚA LA FARMACOCINÉTICA, LA EFICACIA, LA SEGURIDAD Y LA INMUNOGENICIDAD DE BAX 855 (FVIII RECOMBINANTE DE LONGITUD COMPLETA PEGILADO) EN PACIENTES PEDIÁTRICOS CON HEMOFILIA A GRAVE TRATADOS PREVIAMENTE

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A study of the pharmacokinetics, efficacy, safety, and immunogenicity of BAX-855 Administered for Prevention of Bleeding in Previously
Treated Pediatric Patients with Severe Hemophilia A (a blood clotting disorder).

Estudio de farmacocinetica, eficacia, seguridad e inmunogenicidad de BAX-855 administrado para la prevención de hemorragias en pacientes con Hemofilia A grave (un trastorno de la coagulacion de la sangre) tratados previamente.

A.3.2

Name or abbreviated title of the trial where available

BAX 855 Pediatric

BAX 855 pediatrico

A.4.1

Sponsor's protocol code number

261202

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/72/2013

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Baxter Innovations GmbH
B.1.3.4	Country	Austria
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Baxter Innovations GmbH
B.4.2	Country	Austria
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Baxter Innovations GmbH
B.5.2	Functional name of contact point	Eli Taube
B.5.3	Address:
B.5.3.1	Street Address	Industriestrasse 67
B.5.3.2	Town/ city	Vienna
B.5.3.3	Post code	A-1221
B.5.3.4	Country	Austria
B.5.4	Telephone number	+43 (1) 20100 247 1240
B.5.6	E-mail	eli_taube@baxter.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	PEGylated rFVIII
D.3.2	Product code	BAX855 250IU/vial
D.3.4	Pharmaceutical form	Lyophilisate and solvent for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous bolus use (Noncurrent) Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not applicable
D.3.9.2	Current sponsor code	BAX-855
D.3.9.3	Other descriptive name	BAX 855 (PEGYLATED RFVIII)
D.3.9.4	EV Substance Code	SUB90763
D.3.10	Strength
D.3.10.1	Concentration unit	IU international unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	250
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	Yes
D.3.11.13.1	Other medicinal product type	Recombinant product with covalently bound polyethyleneglycol.
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Advate 1000 IU powder and solvent for solution for injection
D.2.1.1.2	Name of the Marketing Authorisation holder	Baxter AG
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Advate
D.3.2	Product code	rAHF-PFM
D.3.4	Pharmaceutical form	Powder and solvent for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	OCTOCOG ALFA
D.3.9.1	CAS number	139076-62-3
D.3.9.4	EV Substance Code	SUB16449MIG
D.3.10	Strength
D.3.10.1	Concentration unit	IU international unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1000
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	PEGylated rFVIII
D.3.2	Product code	BAX855 500IU/vial
D.3.4	Pharmaceutical form	Lyophilisate and solvent for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous bolus use (Noncurrent) Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not applicable
D.3.9.2	Current sponsor code	BAX-855
D.3.9.3	Other descriptive name	BAX 855 (PEGYLATED RFVIII)
D.3.9.4	EV Substance Code	SUB90763
D.3.10	Strength
D.3.10.1	Concentration unit	IU international unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	500
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	Yes
D.3.11.13.1	Other medicinal product type	Recombinant product with covalently bound polyethyleneglycol.
D.IMP: 4
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	PEGylated rFVIII
D.3.2	Product code	BAX855 1000IU/vial
D.3.4	Pharmaceutical form	Lyophilisate and solvent for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous bolus use (Noncurrent) Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not applicable
D.3.9.2	Current sponsor code	BAX-855
D.3.9.3	Other descriptive name	BAX 855 (PEGYLATED RFVIII)
D.3.9.4	EV Substance Code	SUB90763
D.3.10	Strength
D.3.10.1	Concentration unit	IU international unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1000
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	Yes
D.3.11.13.1	Other medicinal product type	Recombinant product with covalently bound polyethyleneglycol.
D.IMP: 5
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	PEGylated rFVIII
D.3.2	Product code	BAX855 2000IU/vial
D.3.4	Pharmaceutical form	Lyophilisate and solvent for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous bolus use (Noncurrent) Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not applicable
D.3.9.2	Current sponsor code	BAX-855
D.3.9.3	Other descriptive name	BAX 855 (PEGYLATED RFVIII)
D.3.9.4	EV Substance Code	SUB90763
D.3.10	Strength
D.3.10.1	Concentration unit	IU international unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1000
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	Yes
D.3.11.13.1	Other medicinal product type	Recombinant product with covalently bound polyethyleneglycol.

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Severe hemophilia A (FVIII<1%)

Hemofilia A grave (FVIII<1%)

E.1.1.1

Medical condition in easily understood language

Hemophilia A

Hemofilia A

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.0
E.1.2	Level	LLT
E.1.2	Classification code	10060612
E.1.2	Term	Hemophilia A
E.1.2	System Organ Class	100000004850

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate FVIII inhibitory antibodies (?0.6 BU using the Nijmegen modification of the Bethesda assay)

Evaluar la incidencia de anticuerpos inhibidores del FVIII (? 0,6
unidades Bethesda [UB] mediante la modificación de Nijmegen del
ensayo Bethesda).

E.2.2

Secondary objectives of the trial

1. To evaluate the PK parameters of BAX 855 in pediatric PTPs <12 years of age.
2. To monitor incremental recovery (IR) of BAX 855 over time.
3. To evaluate hemostatic efficacy of BAX 855 in the management of acute bleeding episodes and for prophylaxis over a period of 6 months.
4. To assess all AEs possibly or probably related to BAX 855.
5. To evaluate immunogenicity (binding antibodies to FVIII, BAX 855, PEG, and Chinese hamster ovary [CHO]) and clinically significant changes in routine laboratory parameters (hematology, clinical chemistry, and lipids) and vital signs.
6. To evaluate changes in HRQoL and health resource use.

1.Evaluar los parámetros farmacocinéticos de BAX 855 en PTP
pediátricos < 12 años de edad.
2.Supervisar la recuperación incremental (RI) de BAX 855 con el tiempo.
3.Evaluar la eficacia hemostática de BAX 855 en el tratamiento de los
episodios hemorrágicos agudos y en la profilaxis durante un período de 6
meses.
4.Evaluar todos los AA posible o probablemente relacionados con BAX
855.
5.Evaluar la inmunogenicidad (anticuerpos de unión frente al FVIII, BAX
855, PEG y las células de ovario de hámster chino [CHO]) y los cambios
clínicamente significativos en los parámetros habituales de laboratorio (hematología, bioquímica clínica, y lípidos) y las constantes vitales.
6.Evaluar los cambios en la CVRS y en la utilización de los recursos
sanitarios

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. The subject has severe hemophilia A (FVIII <1%) as determined by the central laboratory.
2. Subject is <12 years old at the time of screening.
3. Subjects aged ?6 to <12 years of age have been previously treated with plasma-derived and/or rFVIII concentrate(s) for a minimum of 150 EDs (based on the subjects? medical records).
4. Subjects <6 years of age have been previously treated with plasma-derived and/or rFVIII concentrate(s) for at least 50 EDs (based on the subjects? medical records).
5. Subject is human immunodeficiency virus (HIV) negative; or HIV positive with stable disease and CD4+ count of ?200 cells/mm3, as confirmed by central laboratory.
6. The subject and/or legal representative accepts prophylactic treatment over a period of 6 months.
7. The subject and/or the legal representative is willing and able to comply with the requirements of the protocol.

1.El sujeto tiene hemofilia A grave (FVIII < 1 %), según lo determinado
por el laboratorio central.
2.El sujeto tiene < 12 años de edad en el momento de la selección.
3.Los sujetos ? 6 a < 12 años de edad han sido tratados previamente
con algún concentrado derivado de plasma y/o de FVIIIr durante un
mínimo de 150 DE (según los informes médicos de los sujetos).
4.Los sujetos < 6 años de edad han sido tratados previamente con algún
concentrado derivado de plasma y/o de FVIIIr durante un mínimo de 50
DE (según los informes médicos de los sujetos).
5.El sujeto es negativo para el virus de la inmunodeficiencia humana
(VIH); o es VIH positivo con enfermedad estable y un recuento de CD4+
? 200 células/mm3, según lo confirmado por el laboratorio central.
6.El sujeto y/o el representante legal aceptan el tratamiento profiláctico
durante un período de 6 meses.
7.El sujeto y/o el representante legal están dispuestos y son capaces de
cumplir los requisitos del protocolo.

E.4

Principal exclusion criteria

1. Subject has detectable FVIII inhibitory antibodies (?0.4 BU using the Nijmegen modification of the Bethesda assay) as confirmed by central laboratory at screening.
2. Subject has a history of FVIII inhibitory antibodies (?0.4 BU using the Nijmegen modification of the Bethesda assay or ?0.6 BU using the Bethesda assay) at any time prior to screening.
3. Subject has known hypersensitivity towards mouse or hamster proteins, PEG, or Tween 80.
4. Subject has been diagnosed with an inherited or acquired hemostatic defect other than hemophilia A (eg, qualitative platelet defect or von Willebrand?s disease).
5. Subject?s platelet count is <100,000/?L.
6. Subject has severe chronic hepatic dysfunction (eg, ?5 times upper limit of normal [ULN] alanine aminotransferase as confirmed by central laboratory at screening, or a documented international normalized ratio >1.5).
7. Subject has severe renal impairment (serum creatinine >1.5 times ULN).
8. Subject is scheduled to receive during the course of the study, an immunomodulating drug (eg, corticosteroid agents at a dose equivalent to hydrocortisone >10 mg/day, or ?-interferon) other than anti-retroviral chemotherapy.
9. Subject has current or recent (<30 days) use of other PEGylated drugs prior to study participation or is scheduled to use such drugs during study participation.
10. Subject has participated in another clinical study involving an IP or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study.
11. Subject has a medical, psychiatric, or cognitive illness or recreational drug/alcohol use that, in the opinion of the Investigator, would affect subject safety or compliance.
12. Subject?s legal representative is a member of the team conducting this study or is in a dependent relationship with one of the study team members. Dependent relationships include close relatives (ie, children, partner/spouse, siblings, parents) as well as employees of the investigator or site personnel conducting the study.

1.-El sujeto tiene anticuerpos inhibidores del FVIII detectables (? 0,4 UB
mediante la modificación de Nijmegen del ensayo Bethesda), según lo
confirmado por el laboratorio central en la selección
2.El sujeto tiene antecedentes de anticuerpos inhibidores del FVIII (?
0,4 UB mediante la modificación de Nijmegen del ensayo Bethesda o ?
0,6 UB mediante el ensayo de Bethesda) en cualquier momento antes de
la selección.
3.El sujeto tiene una hipersensibilidad conocida a las proteínas de ratón
o hámster, PEG o Tween 80.
4.Al sujeto se le ha diagnosticado un defecto hemostático heredado o
adquirido diferente a la hemofilia A (como un defecto cualitativo de las
plaquetas o la enfermedad de von Willebrand).
5.El recuento plaquetario del sujeto es < 100.000/?l.
6.El sujeto tiene una disfunción hepática crónica grave (p. ej., alanina
aminotransferasa ? 5 veces el límite superior de la normalidad [LSN],
según lo confirmado por el laboratorio central en la selección, o un índice
internacional normalizado documentado > 1,5).
7.El sujeto tiene insuficiencia renal grave (creatinina sérica > 1,5 veces
el LSN).
8.Se ha programado que el sujeto reciba durante el curso del estudio un
fármaco inmunomodulador (como corticosteroides en una dosis
equivalente a hidrocortisona > 10 mg/día o ?-interferón) distinto al de
la quimioterapia antirretroviral.
9.El sujeto utiliza o ha utilizado recientemente (< 30 días) otros
fármacos PEGilados antes de la participación en el estudio o se ha
programado que utilice estos fármacos durante la participación en el
estudio.
10.El sujeto ha participado en otro estudio clínico que utilizó un PEI o un
dispositivo en investigación durante los 30 días anteriores a la
inscripción o está programado que participe en otro estudio clínico con
un PEI o un dispositivo en investigación durante el transcurso de este
estudio.
11.El sujeto tiene una enfermedad médica, psiquiátrica o cognitiva o
consume drogas/alcohol, lo que, en opinión del investigador, podría
afectar a la seguridad o al cumplimiento del sujeto.
12.El representante legal del sujeto es un miembro del equipo que
realiza este estudio o tiene una relación de dependencia con uno de los
miembros del equipo del estudio. Las relaciones dependientes incluyen a
parientes cercanos (es decir, hijos, pareja/cónyuge, hermanos, padres),
así como los empleados del investigador o el personal del centro que
realizan el estudio.

E.5 End points

E.5.1

Primary end point(s)

The primary outcome measure is the incidence of FVIII inhibitory antibodies

La medida prinicpal de los resultados es la incidencia de anticuerpos
inhibidores de FVIII

E.5.1.1

Timepoint(s) of evaluation of this end point

6 months (±2 weeks) or at least 50 EDs

6 meses (± 2 semans) o al menos 50 DEs

E.5.2

Secondary end point(s)

Pharmacokinetics
1. Area under the plasma concentration versus time curve from 0 to ? hours post infusion (AUC0-?), AUC0-?/dose, MRT, clearance (CL), IR, T1/2, volume of distribution at steady state (Vss) following an initial dose of ADVATE followed by BAX 855.
2. IR over time.
Hemostatic Efficacy
1. Annualized bleeding rate (ABR).
2. Consumption of BAX 855: number of infusions and weight-adjusted consumption per month and per year.
3. Number of infusions per bleeding episode, overall hemostatic efficacy rating at resolution of bleed.
4. Weight-adjusted consumption per bleeding episode.
Safety
1. All AEs and SAEs possibly or probably related to BAX 855.
2. Clinical significant changes in vital signs (pulse, respiration, supine blood pressure, and temperature) and clinical laboratory parameters (hematology, clinical chemistry, and lipids).
3. Assessment of binding antibodies to FVIII, BAX 855, PEG, and CHO.

Farmacocinética
1.Área bajo la curva de concentración plasmática frente al tiempo de 0 a
? horas después de la infusión (ABC0-?), ABC0-?/dosis, tiempo medio
de residencia, aclaramiento, RI, semivida de la fase de eliminación,
volumen de distribución en estado de equilibrio después de una dosis
inicial de ADVATE seguida de BAX 855.
2.RI en el tiempo.
Eficacia hemostática
1.Tasa anualizada de hemorragias (TAH).
2.Consumo de BAX 855: número de infusiones y consumo ajustado al
peso por mes y por año.
3.Número de infusiones por episodio hemorrágico, calificación de
eficacia hemostática global cuando desparece la hemorragia.
4.Consumo ajustado al peso por episodio hemorrágico.
Seguridad
1.Todos los AA y los AAG posible o probablemente relacionados con BAX
855.
2.Cambios clínicamente significativos en las constantes vitales (pulso, respiración, presión arterial en posición supina y temperatura) y los
parámetros de laboratorio clínico (hematología, bioquímica clínica y
lípidos).
3.Evaluación de anticuerpos de unión al FVIII, BAX 855, PEG y las CHO.

E.5.2.1

Timepoint(s) of evaluation of this end point

6 months (±2 weeks) or at least 50 EDs

6 meses(±2 semanas) o al menos 50DEs

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Single-group

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Austria

Belgium

Bulgaria

Czech Republic

Germany

Hong Kong

Ireland

Japan

Korea, Republic of

Lithuania

Malaysia

Netherlands

Poland

Romania

Spain

Taiwan

Thailand

Turkey

Ukraine

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

After study completion, subjects will have the option to transition into a continuation study (Baxter Clinical Study 261302)/ to continue receiving BAX 855 until he/she has accumulated a total of 100 EDs or BAX 855 is licensed in his/her country, whichever occurs last.

Después de la finalización del estudio, los sujetos tendrán la opción de hacer la transición a un estudio de continuación (Estudio Clínico de Baxter 261302)/ seguir recibiendo BAX 855 hasta que el/ella hayan acumulado un total de 100 DE o BAX 855 esté autorizado en su país, lo que ocurra mas tarde.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2014-07-25

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-07-09

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2015-10-23

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Orphan Designation Number:
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