Clinical Trials Register

Summary
EudraCT Number:	2006-003148-51
Sponsor's Protocol Code Number:	F13CD-1725
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:	2008-09-23
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

2006-003148-51

A.3

Full title of the trial

A Multi-Centre, Open-Label, Single-Arm and Multiple Dosing Trial on Efficacy and Safety of Monthly Replacement Therapy with Recombinant Factor XIII (rFXIII) in Subjects with Congenital Factor XIII Deficiency.

Studio multicentrico, in aperto, singolo braccio e con somministrazioni multiple per valutare efficacia e sicurezza della terapia sostitutiva mensile con Fattore XIII Ricombinante(rFXIII)nei soggetti con deficit congenito di Fattore XIII.

A.3.2

Name or abbreviated title of the trial where available

F13CD-1725

A.4.1

Sponsor's protocol code number

F13CD-1725

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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	Yes
D.2.5.1	Orphan drug designation number	EU/3/03/179
D.3 Description of the IMP
D.3.1	Product name	Recombinant Factor XIII
D.3.2	Product code	F13CD
D.3.4	Pharmaceutical form	Powder 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	Coagulation factor XIII
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.3	Concentration number	5
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	Yes
D.3.11.13.1	Other medicinal product type	Prodotto da DNA Ricombinante

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 Factor XIII Deficency

Deficit congenito di Fattore XIII

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	14.1
E.1.2	Level	PT
E.1.2	Classification code	10016083
E.1.2	Term	Factor XIII deficiency
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	14.1
E.1.2	Level	PT
E.1.2	Classification code	10061992
E.1.2	Term	Haemophilia
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	14.1
E.1.2	Level	HLT
E.1.2	Classification code	10009737
E.1.2	Term	Coagulation factor deficiencies
E.1.2	System Organ Class	100000004851

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 evaluate the efficacy of monthly replacement therapy with rFXIII on prevention of bleeding episodes in subjects with congenital FXIII deficiency.

Valutare l'efficacia della terapia di sostituzione mensile con il Fattore XIII Ricombinante nella prevenzione di episodi di sanguinamento in pazienti con deficit congenito del Fattore XIII.

E.2.2

Secondary objectives of the trial

-Percentage of subjects without 'bleeding episodes requiring treatment” with a FXIII containing product during the rFXIII treatment period -Rate (number per subject year) of spontaneous ”bleeding episodes requiring treatment” with a FXIII containing product during the rFXIII treatment period -Rate (number per subject year) of traumatic ”bleeding episodes requiring treatment” with a FXIII containing product during the rFXIII treatment period -Rate (number per subject year) of intracranial ”bleeding episodes requiring treatment” with a FXIII containing product during the rFXIII treatment period -Percentage of subjects having a normal clot solubility one hour after rFXIII administration and 28 days after rFXIII administration -Level of FXIII activity one hour after rFXIII administration and 28 days after rFXIII administration -Number of subjects withdrawn from the trial due to lack of efficacy of rFXIII treatment -AEs -Number of subjects with rFXIII antibody development -Number

-% di sogg senza ''episodi di sanguinamento richiedenti tratt'' con prodotto contenente FXIII durante il periodo di tratt con rFXIII-Frequenza di ''episodi di sanguinamento richiedenti tratt'' spontanei con prodotto contenente FXIII durante il periodo di tratt con rFXIII.-Frequenza di ''episodi di sanguinamento richiedenti tratt'' traumatici con prodotto contenente FXIII durante il periodo di tratt con rFXIII.-Frequenza di ''episodi di sanguinamento richiedenti tratt'' intracranici con prodotto contenente FXIII durante il periodo di tratt con rFXIII.-Percentuale di sogg aventi normale profilo di solubilità del coagulo un'ora dopo la sommin di rFXIII e 28 gg dopo la sommin di rFXIII.-Livello di attività del FXIII un'ora dopo la sommin di rFXIII e 28 gg dopo la sommin di rFXIII.-Numero di sogg ritirati dallo studio per mancanza di eff nel tratt con rFXIII.-Eventi Avversi-Numero di sogg con sviluppo di anticorpi per il rFXIII-Numero di sogg con sviluppo di inibitori per il rFXIII.

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 subject). 2.Diagnosis of congenital FXIII A-subunit deficiency (confirmed by genotyping at screening visit). 3.Treatment with regular FXIII replacement therapy initiated at least 6 months prior to screening and one of the following : a documented history of ≥1 treatment-requiring bleeding episode prior to initiation of regular replacement therapy or a documented family history of FXIII congenital deficiency (only for subjects on regular replacement therapy prior to screening). 4.Documented history of ≥ 2 bleeding episodes requiring treatment with FXIII containing blood products within the last 12 months prior to screening (only for subjects receiving on-demand treatment prior to screening). 5.Subjects with age ≥ 6 years and a weight ≥20 kg. 6.If female and of child-bearing potential: negative pregnancy test at screening.

1.Firma del Consenso Informato prima di ogni attivita' relativa allo studio. 2.Diagnosi di deficit congenito della subunita' A del Fattore XIII (confermata da esame di genotipizzazione durante la visita di screening) 3.Trattamento con regolare terapia di sostituzione del fattore XIII, iniziato da almeno 6 mesi prima della visita di screening e uno dei seguenti: una storia documentata di uno o piu' episodi di sanguinamento richiedenti trattamento prima dell'inizio di regolare terapia di sostituzione o una anamnesi di deficit congenito del Fattore XIII (solo per soggetti riceventi regolare terapia di sostituzione prima dello screening). 4.Anamnesi documentata di almeno due o piu' episodi di sanguinamento richiedenti trattamento con prodotti emoderivati contenenti FXIII nei dodici mesi precedenti la visita di screening (solo per soggetti riceventi trattamento ''on demand'' prima della visita di screening). 5.Soggetti con eta' uguale o maggiore di anni 6 di eta' e con peso maggiore od uguale di 20 Kg. 6.Test di gravidanza negativo alla visita di screening per soggetti di sesso femminile in eta' fertile.

E.4

Principal exclusion criteria

1.Known neutralizing antibodies (inhibitors) towards FXIII. 2.Any known congenital or acquired coagulation disorder other than congenital FXIII deficiency. 3.Documented history of two treatment-requiring bleeding episodes per year during previous regular replacement therapy with FXIII containing blood products (FFP, pd FXIII and cryoprecipitate). 4.Platelet count (thrombocytes) < 75 × 109/L. 5.Known or suspected allergy to trial product(s) or related products. 6.Previous participation in this trial. 7.Subject has received treatment with any investigational drug within 30 days of trial enrolment, except pdFXIII. 8.Planned major surgery during the trial period. Catheter, ports and dental extractions do not count as surgeries and will not exclude the subject. 9.Renal insufficiency defined as current dialysis therapy. 10.Any history of confirmed venous or arterial thrombo-embolic events. 11.Subject has received any anti-thrombotic or anti-platelet drugs within 7 days of trial enrollment. 12.Subject has medical, social or psychosocial factors expected to impact compliance or safety. 13.Any disease or condition which, judged by the Investigator, could imply a potential hazard to the subject, interfere with the trial participation or trial outcome. 14.Mental incapacity, unwillingness or language barriers precluding adequate understanding or cooperation in participating in the trial. 15.Females of childbearing potential who are pregnant, breastfeeding or intend to become pregnant or are not using adequate contraceptive methods (adequate contraceptive measures as required by local law or practice) from the time of enrollment to completion of all follow-up trial visits

1.Conosciuta presenza di inibitori contro il FXIII. 2.Qualsiasi altro disordine della coagulazione congenito o acquisito altro rispetto al deficit di Fattore XIII. 3.Anamnesi documentata di piu' di due episodi di sanguinamento richiedenti trattamento in un anno durante precedente terapia sostitutiva con prodotti emoderivati contenenti Fattore XIII (FFP, pd FXIII e crioprecipitati) 4. Conta piastrinica 5. Sospetta o Conosciuta allergia ai prodotti dello studio o a prodotti ad esso correlati. 6. Precedente partecipazione a questo stesso trial 7. Il Soggetto ha ricevuto un trattamento con qualsiasi prodotto sperimentale nei 30 giorni precedenti l'arruolamento in questo studio, con l'eccezzione del pdFXIII. 8. Operazione chirurgica pianificata nel periodo dello studio. Cateteri,ports e estrazioni dentali non rientrano nella definizione di chirurgia e pertanto escludendo il soggetto. 9. Insufficienza Renale definita come concomitante terapia di dialisi. 10. Qualsiasi pregresso di confermato evento trombo embolico arterioso o venoso. 11. Soggetto ha ricevuto un qualsiasi farmaco antitrombotico o antipiastrinico nei 7 giorni precedenti l'arruolamento nello studio. 12. Il Soggetto possiede caratteristiche mediche, sociali o psicosociali che potrebbero inficiare con la corretta adesione allo studio o alla sua sicurezza. 13. Qualsiasi malattia o condizione che, a giudizio dello Sperimentatore, potrebbero costituire un rischio potenziale per il Soggetto, interferendo con la partecipazione allo studio o con la conclusione dello studio. 14. Incapacita' mentale,riluttanza o presenza di barriere linguistiche che possano precludere l'adeguata comprensione o cooperazione alla partecipazione allo studio durante la partecipazione in questo studio. 15. Donne in gravidanza, che stiano allattando o che intendano iniziare una gravidanza, o che non usino adeguati metodi di contraccezione dal momento dell'arruolamento al completamento di tutte le visite di Follow-up.

E.5 End points

E.5.1

Primary end point(s)

Rate (number per subject year) of 'bleeding episodes requiring treatment' with a FXIII containing product during the rFXIII treatment period

Tasso di ''episodi di sanguinamento richiedenti trattamento'' con prodotto contenente FXIII durante il periodo di trattamento con rFXIII.

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

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)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

E.8.1.2

Open

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

Yes

E.8.2.3.1

Comparator description

Tasso di Sanguinamento in Terapia on demand

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

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:

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.1.1.6

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

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

Yes

F.3.3.1

Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2008-09-23.

Yes

F.3.3.2

Women of child-bearing potential using contraception

Yes

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Minori

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)

Alla fine dello studio sara' proposto ai soggetti partecipanti di proseguire con uno studio aggiuntivo di Follow-up con l'utilizzo del prodotto in sperimentazione.

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

2008-07-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2008-07-10

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2010-04-15

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