Clinical Trials Register

Summary
EudraCT Number:	2013-002784-25
Sponsor's Protocol Code Number:	THO-IM_01-CT
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-08-08
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

Spain - AEMPS

A.2

EudraCT number

2013-002784-25

A.3

Full title of the trial

A Phase II, randomized, controlled, double blind study to evaluate the haemostatic efficacy and safety of TT-173 applied in the donor site of patients undergoing skin graft.

Estudio fase II, aleatorizado, controlado, doble ciego para evaluar la eficacia hemostática y la seguridad del TT-173 cuando se aplica a la zona donante de pacientes sometidos a injerto cutáneo.

A.3.1

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

A clinical study to evaluate the efficacy to stop the bleeding and safety of TT-173 applied in the donor site of patients undergoing skin graft.

Estudio clínico para evaluar la eficacia para detener la hemorragia y la seguridad del TT-173 cuando se aplica a la zona donante de pacientes sometidos a injerto cutáneo.

A.4.1

Sponsor's protocol code number

THO-IM_01-CT

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	Thrombotargets Europe
B.1.3.4	Country	Spain
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	Thromobotargets Europe
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Thrombotargets Europe
B.5.2	Functional name of contact point	Jefe de Farmacología
B.5.3	Address:
B.5.3.1	Street Address	Av. Canal Olimpic, s/n
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08860
B.5.3.4	Country	Spain
B.5.4	Telephone number	+34936642040NA
B.5.5	Fax number	+34936350712
B.5.6	E-mail	jesusmurat@thrombotargets.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	TT-173
D.3.2	Product code	TT-173
D.3.4	Pharmaceutical form	Lyophilisate for suspension
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Topical use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Yeast-derived microvesicles containing recombinant Tissue Factor
D.3.9.1	CAS number	NA
D.3.9.2	Current sponsor code	TT-173
D.3.9.3	Other descriptive name	TT-173
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	37
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Oral liquid
D.8.4	Route of administration of the placebo	Topical use (Noncurrent)

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Haemostatic effect in the donor site of patients undergoing skin graft.

Hemostasia de la zona donante de piel en pacientes que requieran la realización de injertos como tratamiento electivo.

E.1.1.1

Medical condition in easily understood language

Stop the bleeding in the donor site after skin graft obtention.

Detención de la hemorragia en la zona donante tras la obtención de un injerto cutáneo.

E.1.1.2

Therapeutic area

Diseases [C] - Injuries, poisonings, and occupational diseases [C21]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	16.0
E.1.2	Level	HLGT
E.1.2	Classification code	10022114
E.1.2	Term	Injuries NEC
E.1.2	System Organ Class	10022117 - Injury, poisoning and procedural complications

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Evaluate the haemostatic efficacy of TT-173 when applied in the donor site of patients undergoing skin graft.

Evaluar la eficacia hemostática del TT-173 cuando se aplica a la zona donante del injerto de piel.

E.2.2

Secondary objectives of the trial

- To assess the systemic absorption of experimental product.
- To assess tolerability and safety of TT-173 when applied on donor site of skin graft.
- To assess immunogenicity of TT-173 when applied on donor site of skin graft.

- Evaluar la absorción sistémica del producto en las condiciones experimentales del estudio.
- Evaluar la tolerabilidad y seguridad del TT-173 cuando se aplica a la zona donante del injerto de piel.
- Evaluar la inmunogenicidad del TT-173 cuando se aplica a la zona donante del injerto cutáneo.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Informed consent signature before any study procedure.
2. Subjects who required skin graft.
3. Subjects older or equal than 18 years at informed consent signature time.
4. Subjects with a skin injury due to a burn or a traumatism which affects at least 20% of body surface.
5. Subjects with a platelet count no compatible with pathology.
6. Subjects with blood cells count no indicative of any situation mentioned in exclusion criteria.
7. Subjects with biochemical results no indicative of any situation mentioned in exclusion criteria.
8. Subjects with coagulation parameters no indicative of any situation mentioned in exclusión criteria.
9. Women potentially fertile must have a negative pregnancy test at inclusion time and agree to use a contraceptive method since informed consent signature until study completion.

1. Sujetos que hayan firmado el consentimiento informado.
2. Sujetos que tengan que someterse a un injerto de piel.
3. Hombre o mujer mayor o igual a 18 años de edad en el momento del consentimiento.
4. Sujetos que presentan una lesión de la piel por quemadura o traumatismo que afecta a menos del 20% de la superficie corporal.
5. Pacientes con un recuento de plaquetas no compatible con patología.
6. Sujetos que presentan resultados de hemograma no indicativos de cualquiera de las situaciones mencionadas en los criterios de exclusión.
7. Sujetos que presentan resultados bioquímicos no indicativos de cualquiera de las situaciones mencionadas en los criterios de exclusión.
8. Sujetos que presentan parámetros de coagulación no indicativos de ninguna de las situaciones mencionadas en los criterios de exclusión.
9. Las mujeres potencialmente fértiles deben presentar una prueba de embarazo negativa, en la inclusión, y deben estar dispuestas a utilizar un método anticonceptivo médicamente aprobado en las relaciones sexuales con posibilidad de concepción desde la firma del consentimiento informado hasta el final del seguimiento de este estudio.

E.4

Principal exclusion criteria

1. Subjects with personal or familiar history of abnormal bleeding episodes.
2. Subjects diagnosed of any kind of congenital or acquired coagulopathy.
3. Subjects with a cutaneous lesion which affects more than 20% of body surface.
4. Subjects affected of any hematologic pathology, cardiopathy, hepatopathy, renal insufficiency, chronic obstructive pulmonary disease, active oncologic process in the last three months or cerebral infarct.
5. Subjects who experienced an excessive bleeding after surgical procedures, deliveries or dental extractions.
6. Subjects affected for any acute infectious disease.
7. Subjects affected for any systemic disease which may contribute to worsening the outcome in case of adverse event (uncontrolled diabetes, uncontrolled hypertension or serious systemic disease).
8. Subjects in treatment with antiplatelet therapy one week and 24 hours prior to the surgery (AAS, triflusal, dipyridamole, clopidogrel, abciximab).
9. Subjects in treatment with oral anticoagulants (antivitamin K, antithrombin drugs and anti-factor Xa), unfractionated heparin, aminocaproic acid and tranexamic acid one week and 24 hours prior to the surgery.
10. Subjects with known hypersensibility to yeast.
11. Subjects who consume abuse drugs other than cannabis and its derivatives.
12. Subjects unable to understand and follow study requirements.
13. Subjects unable of freely given the informed consent or, those who at investigator opinion are not completely reasoned.
14. Subjects who participated in a clinical trial with pharmacologic treatment in the three previous months.
15. Subjects related to the protocol performance such as investigators, collaborators, nursery staff or hospital employees.
16. Subjects with positive serology to HIV, HCV or active infection by HBV.
17. Pregnant or nursing women.

1. Sujetos con antecedentes personales o familiares de episodios hemorrágicos anormales.
2. Sujetos diagnosticados de cualquier tipo de coagulopatías congénitas o adquiridas.
3. Sujetos que presenten una lesión cutánea que afecte a más del 20% de la superficie corporal.
4. Sujetos afectados de cualquier patología hematológica, cardiopatía, hepatopatía, insuficiencia renal, enfermedad pulmonar obstructiva crónica, proceso oncológico activo en los últimos tres meses o infarto cerebral.
5. Sujetos que hayan experimentado un sangrado excesivo después de procedimientos quirúrgicos, partos o extracciones dentales.
6. Sujetos afectados por cualquier enfermedad infecciosa aguda.
7. Sujetos afectados de cualquier enfermedad sistémica que puede empeorar el pronóstico si se produce algún efecto adverso (diabetes no controlada, hipertensión no controlada o enfermedad sistémica grave).
8. Sujetos que deban tomar tratamientos antiagregantes una semana antes y 24 horas después de la cirugía (AAS, triflusal, dipiridamol, clopidogrel, abciximab).
9. Sujetos que deban tomar anticoagulantes orales (anti-vitamina K, fármacos anti-trombina y anti-factor Xa), heparina no fraccionada, ácido aminocaproico y ácido tranexámico una semana antes y 24 horas después de la cirugía.
10. Sujetos con hipersensibilidad o alergia conocida a la levadura.
11. Sujetos que consuman drogas de abuso excluyendo el cannabis y sus derivados.
12. Sujetos que no son capaces de seguir o entender correctamente las instrucciones y los requisitos del estudio.
13. Sujetos que no son libres de dar su consentimiento informado o que a discreción de los investigadores no son completamente razonados.
14. Sujetos que participan o han participado en los últimos tres meses en otro ensayo clínico con tratamiento farmacológico.
15. Sujetos que son los investigadores, colaboradores, personal de enfermería, trabajadores del centro o cualquier otra persona directamente relacionada con el desarrollo del protocolo.
16. Sujetos con serología positiva al VIH o VHC, o que presentan una infección activa por VHB.
17. Mujeres embarazadas o en período de lactancia.

E.5 End points

E.5.1

Primary end point(s)

Hemostasis time: define as the time necessary to stop the bleeding.

Tiempo de hemostasia: se define como el tiempo hasta que cese el sangrado.

E.5.1.1

Timepoint(s) of evaluation of this end point

Every minute up to 10 minutes after the first product application.

Cada minuto hasta los 10 minutos después de la primera aplicación del producto.

E.5.2

Secondary end point(s)

- Product systemic absorption: defined as detectable increase of tisular factor in blood at any evaluation time in comparison with basal level.
- Donor site epithelization: defined as complete or uncomplete.
- Adverse events incidence, severity and seriousness.
- Product immunogenicity: defined as a antibodies reactive detectable increase at 35 ± 5 days to TT-173 product, tisular factor o hexa-histidines.

- Absorción sistémica del producto: se define como un aumento detectable de la concentración en sangre del FT o TT-173 en cualquier momento de la evaluación en comparación con el nivel basal del paciente.
- Epitelización de la zona donante: se define como completa o incompleta.
- Incidencia, intensidad y gravedad de los acontecimientos adversos.
- Inmunogenicidad del producto: definido como un aumento detectable a los 35 ± 5 días de los anticuerpos reactivos contra el producto TT-173, el FT o la cola de hexa-histidinas.

E.5.2.1

Timepoint(s) of evaluation of this end point

At the end of the study .

Al finalizar el estudio.

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

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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

Yes

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

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

Last patient last visit.

Última visita del último paciente.

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

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)

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

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.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)

Standard care.

Tratamiento habitual.

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

2013-10-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-09-11

P. End of Trial
P.	End of Trial Status	Completed

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