Clinical Trials Register

Summary
EudraCT Number:	2010-023803-92
Sponsor's Protocol Code Number:	2010-023803-92
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-07-14
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2010-023803-92

A.3

Full title of the trial

Efficacy and Safety of NNC 0078-0000-0007 in Treatment of Acute Bleeding Episodes in Patients with Congenital Haemophilia and Inhibitors

Efficacia e sicurezza di NNC 0078-0000-0007 nel trattamento di episodi di sanguinamento acuto in pazienti affetti da emofilia congenita con inibitori

A.3.2

Name or abbreviated title of the trial where available

adept™2

A.4.1

Sponsor's protocol code number

2010-023803-92

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	NOVO NORDISK
B.1.3.4	Country	Italy
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	Novo Nordisk A/S
B.4.2	Country	Denmark
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novo Nordisk A/S
B.5.2	Functional name of contact point	Global Clinical Registry
B.5.3	Address:
B.5.3.1	Street Address	Vandtaarnsvej
B.5.3.2	Town/ city	Soeborg
B.5.3.3	Post code	DK-2860
B.5.3.4	Country	Denmark
B.5.4	Telephone number	N/A
B.5.5	Fax number	N/A
B.5.6	E-mail	clinicaltrials@novonordisk.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	rFVIIa analogue
D.3.2	Product code	NNC78-0000-0007
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	vatreptagog alfa (activated)
D.3.9.1	CAS number	897936-89-9
D.3.9.2	Current sponsor code	NNC0078-0000-0007
D.3.10	Strength
D.3.10.1	Concentration unit	µg/kg microgram(s)/kilogram
D.3.10.3	Concentration number	80
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	No
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	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	NOVOSEVEN
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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.3.4	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	Eptacog alfa (activated)
D.3.10	Strength
D.3.10.1	Concentration unit	µg/kg microgram(s)/kilogram
D.3.10.3	Concentration number	90
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	No
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

Congenital Haemophilia and Inhibitors

Emofilia congenita con Inibitori

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	14.0
E.1.2	Level	LLT
E.1.2	Classification code	10053751
E.1.2	Term	Hemophilia A with anti factor VIII
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.0
E.1.2	Level	PT
E.1.2	Classification code	10056494
E.1.2	Term	Haemophilia B with anti factor IX
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To demonstrate the efficacy of rFVIIa analogue in controlling acute bleeds in patients with congenital haemophilia with inhibitors

Dimostrare l’efficacia dell’analogo del rFVIIa nel controllo di sanguinamenti acuti in pazienti con emofilia congenita con inibitori

E.2.2

Secondary objectives of the trial

- To confirm the safety of the rFVIIa analogue when administered for reatment of acute bleeds - To evaluate the immunogenicity of the rFVIIa analogue (formation of neutralising antibodies) - To evaluate the health economics (HE) impact of treatment with the rFVIIa analogue

- Confermare la sicurezza dell’analogo del rFVIIa quando somministrato per il trattamento di sanguinamenti acuti - Valutare l’immunogenicita' dell’analogo del rFVIIa (formazione di anticorpi neutralizzanti) - Valutare gli endpoint per l’impatto sull’economia sanitaria (health economics (HE)) del trattamento con l’analogo del rFVIIa.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Informed consent obtained before any trial-related activities (trial-related activities are any procedure that would not have been performed during normal management of the patient) 2. Male patient with clinical diagnosis of congenital haemophilia A or B and positive inhibitors to coagulation factors VIII or IX (to be confirmed at the Screening Visit -Visit 1) 3. Minimum of five bleeds requiring haemostatic drug treatment within the previous 12 months at trial entry 4. 12 years of age or older 5. For patients when treated at home: The patient or the patients’ caregiver is able (or able to be trained) to reconstitute and administer intravenous trial product, capable of assessing a bleed, efficacy and potential adverse events related to their treatment, and capable of following the trial protocol

1. Il consenso informato ottenuto prima dell’inizio di qualsiasi attivita' connessa allo studio (le attivita' connesse allo studio sono tutte le procedure che non sarebbero state effettuate durante la normale attivita' clinica del soggetto) 2. Paziente maschio con diagnosi clinica di emofilia A o B congenita con positivita' inibitoriale ai fattori di coagulazione VIII o IX (da confermare alla visita di screening -Visita 1) 3. Un minimo di cinque sanguinamenti che abbiano richiesto il trattamento con un prodotto emostatico entro i 12 mesi precedenti l’ingresso nello studio. 4. Soggetto di 12 anni d’eta' o piu' 5. Per i pazienti che si trattano a casa: il paziente o chi se ne prende cura deve essere in grado di (o puo' essere istruito a) ricostituire e somministrare per via endovenosa il prodotto sperimentale, valutare un sanguinamento, l’efficacia ed i potenziali eventi avversi collegabili o meno al trattamento, ed essere in grado di seguire le istruzioni secondo il protocollo dello studio

E.4

Principal exclusion criteria

1. Known or suspected hypersensitivity to trial products or related products 2. Previous participation in this trial defined as withdrawal after administration of trial product 3. Patient has received an investigational medicinal product within 30 days prior to this trial For Brazil, only: The receipt of any investigational drug within one year prior to screening for this trial (Visit 1), unless there, at the investigator discretion, is a direct benefit to the research subject. 4. Congenital or acquired coagulation disorders other than congenital haemophilia A and B 5. Any clinical signs or known history of arterial thrombotic events or previous deep venous thrombosis or pulmonary embolism (as defined by available medical records) 6. Use of any anticoagulant within one week prior to randomisation (e.g. un-fractionated or low molecular weight heparin, vitamin-K antagonists, direct thrombin inhibitors or factor Xa inhibitors)(Use of anticoagulants to lock an implanted Port e.g. Port-A-Cath is allowed ) 7. Platelet count < 50,000 platelets/μl (at the Screening Visit – Visit 1) 8. ALAT > 3 times the normal upper limit (according to laboratory reference ranges) 9. Creatinine level > 1.5 times the normal upper limit (according to laboratory reference ranges) 10. FVIII/IX Immune Tolerance Induction regimens planned to occur during the trial 11. Ongoing bleeding prophylaxis regimens or planned bleeding prophylaxis to occur during the trial 12. HIV positive with current CD4+ count < 200/mL (defined by medical records) 13. Any life-threatening disease or other disease or condition which, according to the Investigator’s judgement, could imply a potential hazard to the patient, interfere with the trial participation or trial outcome

1. Ipersensibilita' nota o sospetta al prodotto sperimentale o ad altri prodotti ad esso correlati 2. Precedente partecipazione allo studio, definita come ritiro dopo la somministrazione del prodotto sperimentale 3. Ricevimento di un prodotto medicinale sperimentale entro 30 giorni prima di questo studio. 4. Disturbi congeniti o acquisiti della coagulazione diversi dall’emofilia congenita A e B 5. Qualsiasi segno clinico o storia nota di eventi trombotici arteriosi o di una precedente trombosi venosa profonda o embolia polmonare (come definiti dalle cartelle cliniche disponibili) 6. Uso di un qualsiasi prodotto anticoagulante entro una settimana prima della randomizzazione (p.es. eparina non frazionata o a basso peso molecolare, antagonisti della vitamina K, inibitori della trombina diretta o inibitori del fattore Xa)( E’ permesso l’uso di anticoagulanti per chiudere un Port, come un Port-A-Cath, impiantato) 7. Conteggio delle piastrine < 50.000 piastrine/μL (durante la visita 1 di screening) 8. ALAT > 3 volte rispetto al valore normale superiore (in base ai range di riferimento del laboratorio) 9. Livello di creatinina > 1.5 volte il valore normale superiore (in base ai range di riferimento del laboratorio) 10. Regimi d’induzione di immunotolleranza di FVIII/IX programmati durante il periodo dello studio 11. Regimi di profilassi per sanguinamenti in corso o profilassi per sanguinamenti programmata durante il periodo dello studio 12. HIV positivo con conteggio effettivo dei CD4+ < 200/mL (definito dalla cartella clinica) 13. Qualsiasi disturbo potenzialmente letale o altra malattia o condizione che, a giudizio dello Sperimentatore, potrebbe implicare un potenziale rischio per il paziente, interferire con la partecipazione allo studio o con il risultato dello studio

E.5 End points

E.5.1

Primary end point(s)

Effective bleeding control: - Effective bleeding control is defined as no additional haemostatic medication (other than trial product) given within 12 hours after first dose of trial product

- Controllo effettivo del sanguinamento. Il controllo effettivo del sanguinamento e' definito da: nessuna ulteriore terapia emostatica (diversa dal prodotto sperimentale) somministrata entro 12 ore dopo la prima dose del prodotto sperimentale.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

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)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Information not present in EudraCT

E.8.1.3

Single blind

Information not present in EudraCT

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Information not present in EudraCT

E.8.1.7.1

Other trial design description

sequenza random di due regimi di trattamento

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Novoseven

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

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

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	Yes
F.1.1	Number of subjects for this age range:	0
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	Yes
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	Yes
F.2 Gender
F.2.1	Female	No
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	No
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	No
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	4
F.4.2	For a multinational trial
F.4.2.1	In the EEA	60
F.4.2.2	In the whole clinical trial	60

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

2011-04-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-04-19

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2012-08-13

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