Clinical Trials Register

Summary
EudraCT Number:	2011-002403-15
Sponsor's Protocol Code Number:	Forma-01
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2013-04-15
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

2011-002403-15

A.3

Full title of the trial

A prospective, controlled, randomised, cross-over study investigating the pharmacokinetic properties, surrogate efficacy and safety of Octafibrin
compared to Haemocomplettan® P/ RiaSTAPTM in subjects with congenital fibrinogen deficiency

Uno studio di cross-over prospettico, controllato, randomizzato che analizza le proprietà farmacocinetiche, l'efficacia e la sicurezza di Octafibrin rispetto a Haemocomplettan® P/ RiaSTAPTM in soggetti con deficit congenito di fibrinogeno

A.3.1

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

A controlled, randomised, study investigating the
pharmacokinetic properties (to see how active the study drug is in your blood and how long it takes for the study drug to get out of your blood) ,
surrogate efficacy and safety of Octafibrin compared to
Haemocomplettan® P/ RiaSTAPTM in subjects with congenital fibrinogen deficiency

Uno studio controllato, randomizzato che analizza le proprietà farmacocinetiche (per vedere come agisce il farmaco in studio nel sangue e quanto tempo occorre prima che sia escreto dal sangue), l'efficacia e la sicurezza di Octafibrin rispetto a Haemocomplettan® P/ RiaSTAPTM in soggetti con deficit congenito di fibrinogeno

A.4.1

Sponsor's protocol code number

Forma-01

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	OCTAPHARMA 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	OCTAPHARM
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	BIOIKOS FARMA S.R.L.
B.5.2	Functional name of contact point	PROJECT MONITORING
B.5.3	Address:
B.5.3.1	Street Address	VIA G. LEOPARDI N. 6
B.5.3.2	Town/ city	BOLOGNA
B.5.3.3	Post code	40122
B.5.3.4	Country	Italy
B.5.4	Telephone number	00390512966411
B.5.5	Fax number	00390512966490
B.5.6	E-mail	morgagni@bioikos.it

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	octafibrin
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	HUMAN FIBRINOGEN
D.3.9.1	CAS number	9001-32-5
D.3.9.3	Other descriptive name	HUMAN FIBRINOGEN
D.3.9.4	EV Substance Code	SUB12502MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/kg milligram(s)/kilogram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	70
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	Yes
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	Haemocomplettan® P
D.2.1.1.2	Name of the Marketing Authorisation holder	CSL Behring GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Haemocomplettan® P
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	HUMAN FIBRINOGEN
D.3.9.1	CAS number	9001-32-5
D.3.9.3	Other descriptive name	HUMAN FIBRINOGEN
D.3.9.4	EV Substance Code	SUB12502MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/kg milligram(s)/kilogram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	70
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	Yes
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 fibrinogen deficiency

deficit congenito di fibrinogeno

E.1.1.1

Medical condition in easily understood language

deficency of fibrinogen in human plasma

deficit di fibrinogeno nel plasma umano

E.1.1.2

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

MedDRA Classification

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 determine the single dose pharmacokinetics of Octafibrin and Haemocomplettan® P/RiaSTAPTM in subjects with congenital fibrinogen deficiency
• To determine maximum clot strength (maximum clot firmness [MCF]) as a surrogate marker for haemostatic efficacy before and after
administration of Octafibrin and Haemocomplettan® P/ RiaSTAPTM in
subjects with congenital fibrinogen deficiency

 Determinare la farmacocinetica della singola dose di Octafibrin e
Haemocomplettan ® P / RiaSTAPTM in soggetti con deficit congenito di fibrinogeno
 Determinare la stabilità massima del coagulo (maximum clot firmness [MCF]) come marker surrogato per l'efficacia emostatica prima e dopo la somministrazione di Octafibrin ed Haemocomplettan ® P / RiaSTAPTM in
soggetti con deficit congenito del fibrinogeno

E.2.2

Secondary objectives of the trial

To assess the safety of Octafibrin in subjects with congenital fibrinogen deficiency

Valutare la sicurezza di Octafibrin in soggetti con deficit congenito di fibrinogeno

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Subject age ≥12 years
• Documented congenital fibrinogen deficiency (afibrinogenaemia)
Plasma fibrinogen activity and antigen at screening bellow detection limit (i.e. <20mg/dl)
• Informed consent signed by subject or legal guardian

 età ≥ 12 anni
 deficit congenito di fibrinogeno documentato (afibrinogenaemia)
Attività plasmatica del fibrinogeno e antigene allo screening al di sotto del limite di rilevamento (cioè <20mg/dl)
 consenso informato firmato dal soggetto o dal suo rappresentante legale

E.4

Principal exclusion criteria

• Life expectancy <6 months
• Bleeding disorder other than congenital fibrinogen deficiency
• Dysfibrinogenemia
• Treatment with:
Any fibrinogen concentrate or other fibrinogen-containing blood product in the 2 weeks prior to enrolment
• Presence or history of:
Hypersensitivity to study medication
Deep vein thrombosis or pulmonary embolism within 1 year prior to enrolment
Arterial thrombosis within 1 year prior to enrolment
Hypersensitivity to human plasma proteins
 Acute bleeding
 History of oesophageal varicose bleeding
 End-stage liver disease (i.e. Child-Pugh-score B or C)
 Planned major surgery with a need for blood transfusion during the PK blood-sampling period of this study
 Pregnancy, or an intention to become pregnant during the study
 Currently breast-feeding, or with the intention of breast-feeding during the study
 HIV positive with a viral load >200 particles/μl ~ >400000 copies/ml
 Polytrauma 1 year prior to enrolment
 Suspicion of an anti-fibrinogen inhibitor as indicated by previous in-vivo recovery, if available <0.5 (mg/dl)/(mg/kg), (there is currently no standard test for inhibitors)
 Blood or plasma donation in the 3 months prior to enrolment

 Aspettativa di vita < di sei mesi
 Disturbo della coagulazione differente dal deficit congenito del fibrinogeno
 Disfibrinogenemia
 Terapia con:
- qualsiasi concentrato di fibrinogeno o altro prodotto ematico
contenente fibrinogeno nelle due settimane precedenti il reclutamento
 Presenza o storia di:
- ipersensibilità al farmco in studio
- trombosi venosa profonda o embolia polmonare entro l'anno
precedente il reclutamento
- trombosi arteriosa entro l'anno precedente il reclutamento
- ipersensibilità alle proteine plasmatiche umane
 emorragia acuta
 storia di emorragia varicosa esofagea
 patologia epatica all'ultimo stadio (con punteggio Child-Pugh B o C)
 Importante intervento chirurgico programmato con necessità di
trasfusione ematica durante il priodo di campionamento ematico
farmacocinetico di questo studio
 Gravidanza, o un'intenzione di avviare una gravidanza durante lo studio
 Allattamento, o l'intenzione di avviare l'allattamento durante lo studio
 HIV positivo con carico virale > di 200 particelle/μl ~ >400000
copies/ml
 Politrauma 1 anno prima del reclutamento
 Sospetto di inibitore anti-fibrinogeno come indicato da precedente ripreso in-vivo, se disponibile <0.5 (mg/dl)/(mg/kg), (non sono
attualmente disponibili test standard per gli inibitori)
 Donazione di sangue o plasma nei tre mesi precedenti il reclutamento

E.5 End points

E.5.1

Primary end point(s)

A comparison of the AUC between Octafibrin and Haemocomplettan®
P/RiaSTAPTM
Surrogate endpoint for haemostatic efficacy
Comparison of MCF between Octafibrin and Haemocomplettan®
P/RiaSTAPTM at 1 hour post-infusion

Un confronto dell'AUC tra Octafibrina e Haemocomplettan®
P/RiaSTAPTM
Endpoint surrogato per l'efficacia emostatica:
Confronto della MCF tra Octafibrina ed Haemocomplettan® P/RiaSTAPTM
a 1 ora dopo l'infusione

E.5.1.1

Timepoint(s) of evaluation of this end point

at baseline, 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216 and 312 hours postinfusion.

al basale, 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216 e 312 ore dopo l'infusione

E.5.2

Secondary end point(s)

• To compare the in vivo recovery between Octafibrin and
Haemocomplettan® P/ RiaSTAPTM
• To compare the pharmacokinetics between Octafibrin and
Haemocomplettan® P/ RiaSTAPTM
• To document the safety of Octafibrin

 Confrontare il recupero in vivo tra Octafibrina ed Haemocomplettan®
P/ RiaSTAPTM
 Confrontare la farmacocinetica tra Octafibrina ed Haemocomplettan®
P/ RiaSTAPTM
 Documentare la sicurezza di Octafibrina

E.5.2.1

Timepoint(s) of evaluation of this end point

at baseline, 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216 and 312 hours postinfusion.

al basale, 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216 e 312 ore dopo l'infusione

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

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)

Yes

E.7.1.1

First administration to humans

Yes

E.7.1.2

Bioequivalence study

Yes

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)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

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

Yes

E.8.1.7

Other

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

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

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

Bulgaria

Germany

Iran, Islamic Republic of

Italy

Spain

Turkey

United Kingdom

United States

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

LAST PATIENT LAST VISIT

ULTIMA VISITA DELL'ULTIMO PAZIENTE

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)

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

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

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 2013-04-15.

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

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)

NONE

NESSUNO

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

2013-03-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-05-14

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2013-11-28

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