Clinical Trials Register

Summary
EudraCT Number:	2009-013056-71
Sponsor's Protocol Code Number:	TC-2402-038-SP
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2009-11-05
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

France - ANSM

A.2

EudraCT number

2009-013056-71

A.3

Full title of the trial

TachoSil versus current practice in dura sealing techniques for the prevention of postoperative cerebrospinal fluid (CSF) leaks in patients undergoing skull base surgery: An open label, randomised, controlled, multicentre, parallel group efficacy and safety trial.

A.3.2

Name or abbreviated title of the trial where available

TASALL -TachoSil Against Liquor Leak

A.4.1

Sponsor's protocol code number

TC-2402-038-SP

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Nycomed Danmark ApS
B.1.3.4	Country	Denmark
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	Yes
D.2.1.1.1	Trade name	TachoSil medicated sponge
D.2.1.1.2	Name of the Marketing Authorisation holder	Nycomed Austria GmbH
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	TachoSil
D.3.4	Pharmaceutical form	Medicated sponge
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Local use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Human Thrombin
D.3.9.1	CAS number	0
D.3.9.3	Other descriptive name	THROMBIN, HUMAN
D.3.10	Strength
D.3.10.1	Concentration unit	IU international unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2.0
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.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5.5
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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	TachoSil medicated sponge
D.2.1.1.2	Name of the Marketing Authorisation holder	Nycomed Austria GmbH
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	TachoSil
D.3.4	Pharmaceutical form	Medicated sponge
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Local use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	HUMAN THROMBIN
D.3.9.1	CAS number	0
D.3.9.3	Other descriptive name	THROMBIN, HUMAN
D.3.10	Strength
D.3.10.1	Concentration unit	IU international unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2.0
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.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5.5
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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

Skull base surgery for the prevention of postoperative cerebrospinal fluid (CSF) leaks

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	12.0
E.1.2	Level	PT
E.1.2	Classification code	10067908
E.1.2	Term	Neurosurgery

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective is to assess the efficacy of TachoSil as an adjunct in sealing the dura mater in order to prevent postoperative CSF-leakage / clinically evident pseudomeningocele following skull base surgery.

E.2.2

Secondary objectives of the trial

The secondary objective is to assess the safety of TachoSil as an adjunct in sealing the dura mater to prevent postoperative CSF-leakage / clinically evident pseudomeningocele following skull base surgery.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Pre-operative Inclusion Criteria – positive response required for inclusion:
1. Has written informed consent been obtained according to local regulations before any trial-related activities? (A trial-related activity is any procedure that would not have been performed during the routine management of the patient.)
2. Is the patient able and willing to comply with the procedures required for trial completion?
3. Is the patient 18 years or above?
4. Is the patient to undergo non-trauma related neurosurgery for pathology of the skull base resulting in opening and closing of the dura mater? Dura substitution is allowed.

Intra-operative Inclusion Criteria – positive response required for inclusion:
5. Is the Surgical Wound Classification Class of class I (Clean surgical wound)?
6. Is the surgical approach/procedure consistent with skull base surgery? I.e. at least one of
the following:
a. Lateral approach to the foramen magnum: far lateral, extreme lateral,
anterolateral, posterolateral,
b. Approach to the jugular foramen: infratemporal, juxta condylar, transjugular,
c. Approach to the cerebello pontine (CP) angle and petrous apex retrosigmoïd,
translabyrinthine, retrolabyrinthine, transcochlear (limited transpetrosal),
d. Approach to the middle fossa: subtemporal (+/- petrous apex drilling),
pterional approach (any fronto temporal approach +/- orbitozygomatic
deposition),
e. Approach to the anterior fossa: subfrontal (uni or bilateral),
f. Approach to the midline posterior fossa or paramedian posterior fossa.

E.4

Principal exclusion criteria

Pre-operative Exclusion Criteria – negative response required for inclusion:
1. Has the patient participated in another clinical trial with an investigational drug or device within 28 days of inclusion in this trial? (Participation in non-interventional trials is allowed)
2. Has the patient previously participated in this trial?
3. Does the patient have evidence of an infection indicated by any one of the following:
fever >101°F / 38.5°C, white blood cells (WBC) <3.5/GL or >13.0/GL (if patient on steroid treatment up to 20.00/GL), positive urine culture, positive blood culture, positive chest Xray?
4. Does the patient have a known coagulopathy?
5. Does the patient have a history of allergic reactions after application of human
fibrinogen, human thrombin and / or collagen of any origin?
6. Is the patient anticipated to need additional neurosurgery within the follow-up period of Week 7±1 at the same surgical site?

For females of childbearing potential, i.e. neither postmenopausal (less than 12 month after the last menstruation) nor permanently sterilised (e.g. tubal occlusion, hysterectomy, bilateral salpingectomy):
7. Does the female patient use an unacceptable contraceptive method or method
ineffective at the time of randomisation, i.e. do not use a contraceptive method which is a highly effective method of birth control; defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intrauterine devices or vasectomised partner?
8. Has the female patient had a positive serum pregnancy test taken up to 5 days prior to surgery? All females not documented as postmenopausal or permanently sterile must have a serum pregnancy test performed.
9. Breastfeeding?

Intra-operative Exclusion Criteria – negative response required for inclusion:
10. The surgical approach/procedure is consistent with any transcranial or transfacial or combination of transcranial – transfacial approaches with wide defect in the skull base?
I.e. any of the following:
g. Trans basal approach,
h. Total petrosectomy,
i. Trans facial approach,
j. Trans sphenoïdal approach,
k. Endoscopic procedures,
l. Trans oral approach (and any extension: Le Fort, mandibulotomy).
11. Did the arachnoid membrane remained intact during surgery and/or the liquor containing system?

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is the occurrence of either a clinically evident CSF-leak or a clinically evident pseudomeningocele

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

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

Standard treatment for closure of the dura or duraplasty

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

Information not present in EudraCT

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

E.8.7

Trial has a data monitoring committee

Yes

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

The end-of-trial is defined as last patient last visit.

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	No
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)	No
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	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	Yes
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	57
F.4.2	For a multinational trial
F.4.2.1	In the EEA	550
F.4.2.2	In the whole clinical trial	726

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

2009-11-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2009-12-03

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-06-27

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