Clinical Trials Register

Summary
EudraCT Number:	2018-003655-37
Sponsor's Protocol Code Number:	19764
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2019-06-11
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

2018-003655-37

A.3

Full title of the trial

Post-marketing investigation (PMI) to assess safety and efficacy of Jivi® (BAY 94-9027) treatment in patients with hemophilia A

Ensayo posautorización para evaluar la seguridad y la eficacia del tratamiento con Jivi® (BAY 94-9027) en participantes con hemofilia A

A.3.1

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

Jivi interventional PMI study to assess safety and efficacy

Ensayo para evaluar la seguridad y la eficacia de Jivi

A.4.1

Sponsor's protocol code number

19764

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Bayer Consumer Care AG
B.1.3.4	Country	Switzerland
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	Bayer Consumer Care AG
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Bayer HealthCare AG
B.5.2	Functional name of contact point	Bayer Clin. Trials Contact CTP Team
B.5.3	Address:
B.5.3.1	Street Address	Bayer Pharma AG, S102, Level 2, Room 156
B.5.3.2	Town/ city	Berlin
B.5.3.3	Post code	4052
B.5.3.4	Country	Germany
B.5.6	E-mail	clinical-trials-contact@bayerhealthcare.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	Yes
D.2.1.1.1	Trade name	Jivi®
D.2.1.1.2	Name of the Marketing Authorisation holder	Bayer 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	Jivi (1000 IU/vial)
D.3.2	Product code	BAY 94-9027
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	DAMOCTOCOG ALFA PEGOL
D.3.9.2	Current sponsor code	BAY 94-9027
D.3.9.3	Other descriptive name	PEGylated B-domain deleted recombinant human antihemophilic Factor VIII
D.3.9.4	EV Substance Code	SUB187618
D.3.10	Strength
D.3.10.1	Concentration unit	IU/ml international unit(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	400
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: 2
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	Yes
D.2.1.1.1	Trade name	Jivi®
D.2.1.1.2	Name of the Marketing Authorisation holder	Bayer 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	Jivi (2000 IU/vial)
D.3.2	Product code	BAY 94-9027
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	DAMOCTOCOG ALFA PEGOL
D.3.9.2	Current sponsor code	BAY 94-9027
D.3.9.3	Other descriptive name	PEGylated B-domain deleted recombinant human antihemophilic Factor VIII
D.3.9.4	EV Substance Code	SUB187618
D.3.10	Strength
D.3.10.1	Concentration unit	IU/ml international unit(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	800
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	Yes
D.2.1.1.1	Trade name	Jivi®
D.2.1.1.2	Name of the Marketing Authorisation holder	Bayer 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	Jivi (3000 IU/vial)
D.3.2	Product code	BAY 94-9027
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	DAMOCTOCOG ALFA PEGOL
D.3.9.2	Current sponsor code	BAY 94-9027
D.3.9.3	Other descriptive name	PEGylated B-domain deleted recombinant human antihemophilic Factor VIII
D.3.9.4	EV Substance Code	SUB187618
D.3.10	Strength
D.3.10.1	Concentration unit	IU/ml international unit(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1200
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: 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	Yes
D.2.1.1.1	Trade name	Jivi®
D.2.1.1.2	Name of the Marketing Authorisation holder	Bayer 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	Jivi (500 IU/vial)
D.3.2	Product code	BAY 94-9027
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	DAMOCTOCOG ALFA PEGOL
D.3.9.2	Current sponsor code	BAY 94-9027
D.3.9.3	Other descriptive name	PEGylated B-domain deleted recombinant human antihemophilic Factor VIII
D.3.9.4	EV Substance Code	SUB187618
D.3.10	Strength
D.3.10.1	Concentration unit	IU/ml international unit(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	200
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.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

Hemophilia A

Hemofilia A

E.1.1.1

Medical condition in easily understood language

Deficiency of clotting factor Factor VIII

Deficiencia de factor de coagulación Factor VIII

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	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10060613
E.1.2	Term	Hemophilia A (Factor VIII)
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

Assess general safety of Jivi® safety a with specific focus on immunogenicity and inhibitor documentation in a routine clinical use of the product in at least additional 25 participants during 100 ED in order to fully comply with Guideline requirements of 200 participants observed for at least 100 ED including participants from pre-authorization studies.

Evaluar la seguridad general de Jivi® focalizándose en la inmunogenicidad y la documentación de inhibidores en un uso clínico rutinario del producto en al menos 25 participantes adicionales durante 100 DE para cumplir por completo con los requisitos de la guía de la EMA de que 200 participantes sean observados con al menos 100 DE incluyendo participantes de ensayos previos a la autorización.

E.2.2

Secondary objectives of the trial

Assess clinical efficacy of Jivi

Evaluar la eficacia clínica de Jivi

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Participants must ≥ 18 years of age inclusive, at the time of signing the informed consent
2. Participants with severe hemophilia A (FVIII: C<1%)
3. PTPs (≥150 ED) on prophylaxis treatment before enrollment
4. Participants who are immunocompetent. If human immunodeficiency virus (HIV) positive, cluster of differentiation 4 (CD4)+ lymphocyte count >200/mm3
5. Participants who are willing to complete an eDiary
6. Male participants
7. Capable of giving signed informed consent as described in Section 10.1.3 of the protocol which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol

1. Los participantes deben tener ≥ 18 años de edad inclusive en el momento de firmar el consentimiento informado
2. Participantes con hemofilia A grave (concentración de FVIII <1%).
3. Pacientes tratados previamente (≥150 DE) en tratamiento profiláctico antes de la selección.
4. Participantes que sean inmunocompetentes. En el caso de pacientes positivos para el virus de inmunodeficiencia humana (VIH), el recuento de linfocitos (CD4)+ debe ser > 200/mm3.
5. Participantes que estén dispuestos a completar un diario electrónico.
6. Participantes varones
7. Capaces de dar un consentimiento informado firmado tal y como se describe en la Sección 10.1.3 del protocolo, el cual incluye el cumplimiento de los requisitos y restricciones enumerados en el formulario de consentimiento informado y en el protocolo.

E.4

Principal exclusion criteria

1. Any other inherited or acquired bleeding disorder in addition to Hemophilia A.
2. Platelet count < 100,000/mm3
3. The participant has a planned major surgery.
4. The participant is currently participating in another investigational drug study, or has participated in a clinical study involving an investigational drug within 30 days of signing informed consent or previous treatment in a clinical phase III study with BAY 94-9027 (now marketed as Jivi®).
5. Current evidence (by central laboratory) or history of inhibitor to FVIII with a titer ≥ 0.6 Bethesda unit (BU).
6. Known hypersensitivity to the drug substance, excipients, or mouse or hamster protein.
7. Creatinine > 2x upper limit of normal
8. AST or ALT > 5x upper limit of normal (AST: aspartate aminotransferase; ALT: alanine aminotransferase)

1. Cualquier otro trastorno hemorrágico hereditario o adquirido además de la hemofilia A
2. Recuento de plaquetas <100,000/mm3
3. Participantes que tengan una cirugía mayor planificada
4. Participantes que están participando actualmente en otro ensayo con un fármaco en investigación o hayan participado en un ensayo clínico con un fármaco en investigación dentro de los 30 días posteriores a la firma del consentimiento informado o hayan sido tratados previmente en un ensayo clínico fase III con BAY 94-9027 (ahora se comercializa como Jivi®).
5. Evidencia actual (mediante laboratorio central) o historia de inhibidores del FVIII con un valor ≥ 0,6 unidad de Bethesda (UB).
6. Hipersensibilidad conocida al fármaco del ensayo, excipientes o proteína de ratón o hámster.
7. Creatinina> 2 veces el límite superior de la normalidad.
8. AST o ALT> 5 veces el límite superior de la normalidad (AST: aspartato-aminotransferasa; ALT: alanina-aminotransferasa)

E.5 End points

E.5.1

Primary end point(s)

Safety:
FVIII inhibitor development by the Nijmegen Bethesda assay.

Seguridad:
Aparición del inhibidor de FVIII mediante el ensayo Nijmegen Bethesda.

E.5.1.1

Timepoint(s) of evaluation of this end point

Continuous throughout the study.

Continuamente durante todo el ensayo.

E.5.2

Secondary end point(s)

Safety:
Treatment-emergent adverse events (TEAE)
Development of treatment-emergent anti-PEG antibodies

Clinical Efficacy:
Annualized bleeding rate (ABR)

Seguridad:
Acontecimientos adversos aparecidos durante el tratamiento (AADT)
Aparición de anticuerpos anti-PEG durante el tratamiento

Eficacia clínica:
Tasa anualizada de hemorragias (TAH)

E.5.2.1

Timepoint(s) of evaluation of this end point

Throughout the study

Durante todo el ensayo

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

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)

E.7.4

Therapeutic use (Phase IV)

Yes

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

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.8.2.4

Number of treatment arms in the trial

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

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

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

A participant is considered to have completed the study if he has completed all phases of the study including the last visit or the last scheduled procedure shown in the Schedule of Activities. If more than 25 participants are included, all participants will be treated for at least 6 months, but not all participants may reach 100 ED at the end of the study.
The end of the study is defined as the date of the clean database.

Se considera que un participante ha completado el ensayo si ha completado todas las fases del ensayo, incluida la última visita o el último procedimiento programado que se muestra en el calendario de actividades. Si se incluyen más de 25 participantes, todos los participantes recibirán tratamiento durante al menos 6 meses, pero no todos los participantes pueden alcanzar los 100 DE al final del ensayo.
El final del ensayo se define como la fecha del cierre de la base de datos.

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 years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

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)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

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 the end of the study, the participants will be offered the option to participate in a non-interventional PASS study, that will be independent from this study.

Una vez finalizado el ensayo, a los participantes se les ofrecerá la opción de participar en un estudio de seguridad postautorización no intervencionista, que será independiente de este ensayo.

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

2019-09-11

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-07-24

P. End of Trial
P.	End of Trial Status	Ongoing

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