Clinical Trials Register

Summary
EudraCT Number:	2011-002403-15
Sponsor's Protocol Code Number:	Forma-01
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-02-06
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

Germany - PEI

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

Eine prospektive, kontrollierte, randomisierte klinische Prüfung im Cross-Over-Design zur Untersuchung der pharmakokinetischen Eigenschaften, Surrogat-Wirksamkeit und Sicherheit von Octafibrin im Vergleich zu Haemocomplettan® P/ RiaSTAPTM bei Patienten mit angeborenem Fibrinogenmangel

A.3.1

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

A controlled, randomised, study investigating the pharmacokineticproperties (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

Eine kontrollierte, randomisierte, Studie zur Untersuchung der pharmakologischen Eigenschaften (was geschieht mit dem Medikament im Körper und wie lange dauert es, bis dieses ausgeschieden ist), Wirksamkeit der Ersatz-Therapie und Sicherheit von Octafibrin im Vergleich zu Haemocomplettan® P/ RiaSTAPTM bei Patienten mit angeborenem Fibrinogenmangel.

A.3.2

Name or abbreviated title of the trial where available

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

P/200/2012

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	QED Clinical Services Limited
B.5.2	Functional name of contact point	PROJECT COORDINATOR
B.5.3	Address:
B.5.3.1	Street Address	The Learning House, Snowdon Drive, Winterhill
B.5.3.2	Town/ city	Milton Keynes
B.5.3.3	Post code	MK6 1BP
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+441908251480
B.5.5	Fax number	+441908251499
B.5.6	E-mail	hwide@qed-clinical.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	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 (afibrinogenaemia) defined as plasma fibrinogen activity and antigen at screening below detection limit (i.e. <20mg/dl)

Angeborener Fibrinogenmangel (Afibrinogenämie). Die Werte für die Plasma Fibrinogen Aktivität und Antigen sind unter der Nachweisgrenze (<20 mg/dl).

E.1.1.1

Medical condition in easily understood language

Congenital deficiency of coagulation factor fibrinogen (afibrinogenaemia), wherby the coagulation of blood is delayed or impossible.

Angeborenes Fehlen des Gerinnungsfaktors Fibrinogen (Afibrinogenämie), wodurch die Blutgerinnung verzögert wird oder nicht mehr möglich ist.

E.1.1.2

Therapeutic area

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

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10052651
E.1.2	Term	Afibrinogenaemia
E.1.2	System Organ Class	100000004850

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

• Bestimmen der Pharmakokinetik nach Einmalgabe von Octafibrin und Haemocomplettan® P/RiaSTAPTM bei Patienten mit angeborenem Fehlen von Fibrinogen.
• Bestimmen der Gerinnselfestigkeit (maximum clot firmness [MCF]) als Ersatzmarker für die Effizienz der Blutstillung vor und nach Gabe von Octafibrin und Haemocomplettan® P/ RiaSTAPTM bei Patienten mit angeborenem Fehlen von Fibrinogen.

E.2.2

Secondary objectives of the trial

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

Bewerten der Sicherheit von Octafibrin bei Patienten mit angeborenem Fehlen von Fibrinogen.

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

Patientenalter ≥12 Jahre
• Dokumentiertes angeborenes Fehlen von Fibrinogen (Afibrinogenämie)
Plasma Fibrinogenaktivität und Antigen unter der Nachweisgrenze (<20mg/dl)
• Vom Patienten oder Vormund unterschriebene Patienten-einverständniserklärung.

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 the 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
• Blood or plasma donation in the 3 months prior to enrolment

• Lebenserwartung <6 Monate
• Andere, außer angeborenes Fehlen des Fibrinogens, Blutungsstörung
• Dysfibrinogenämie
• Behandlung mit:
Jedem anderen Fibrinogenkonzentrat oder anderem Fibrinogen enthaltenden Blutprodukt in den 2 Wochen vor Aufnahme in die Studie.
• Vorhandensein oder Historie von:
Überempfindlichkeit gegen die Studienmedikation
Tiefe Venenthrombose ein Jahr vor Studienaufnahme
Arterielle Thrombose ein Jahr vor Studienaufnahme
Überempfindlichkeit auf Humanplasmaprotein
• Akute Blutungen
• Blutungsvergangenheit oesophagaler Varizen
• Lebererkrankung im Endstadium (d.h. Child-Pugh-Score B oder C)
• Geplante größere Operation mit der Notwendikeit der Bluttransfusion während der PK Probenentnahme Periode dieser Studie
• Schwangerschaft oder die Intention während der Studie schwanger zu werden
• Stillend oder die Intention während der Studie zu Stillen
• HIV Positiv mit einer viralen Belastung von >200 Partikeln/ μl ~ >400000 Kopien/ml
• Polytrauma 1 vor Aufnahme in die Studie
• Blut-oder Plasmaspende in den 3 Monaten vor Aufnahme in die Studie

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

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 post-infusion.

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

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 post-infusion.

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)

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)

Yes

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

Yes

E.8.4

The trial involves multiple sites in the 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

Switzerland

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

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 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 2012-02-06.

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

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

2013-06-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-03-20

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2015-01-19

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