Clinical Trials Register

Summary
EudraCT Number:	2012-003390-26
Sponsor's Protocol Code Number:	BSG-12
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:	2012-11-29
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

2012-003390-26

A.3

Full title of the trial

Open, Blindly Evaluated, Prospective, Controlled, Randomized, Multicenter Phase III Clinical Trial to Compare Intra-individually the Efficacy and Tolerance of Oleogel-S10 versus Standard of Care in Accelerating the Wound Healing of Split-Thickness Skin Graft Donor Sites

Ensayo clínico multicéntrico de fase III abierto, prospectivo, controlado y aleatorizado, con evaluación enmascarada, para comparar intraindividualmente la eficacia y tolerabilidad de Oleogel- S10 con las del tratamiento de referencia para acelerar la cicatrización de la zona donante en injertos de piel de espesor parcial.

A.3.1

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

Unblinded Designed, Evaluated by Blinded Experts, Prospective, Controlled, Randomized, Multicenter Phase III Clinical Trial to Compare within each single patient the Efficacy and Tolerance of Oleogel-S10 versus Standard of Care in Accelerating the Healing of Split-Thickness Skin Graft Donor Sites

Ensayo clínico multicéntrico de fase III, de diseño abierto para investigador y paciente, evaluado por expertos en la materia ciegos al tratamiento, prospectivo, controlado y aleatorizado, para comparar en un mismo paciente la eficacia y tolerabilidad de Oleogel-S10 frente al tratamiento de referencia para acelerar la cicatrización en de la zona donante en injertos de piel de espesor parcial

A.3.2

Name or abbreviated title of the trial where available

Oleogel-S10 in Split-Thickness Skin Graft Donor Sites

Oleogel-S10 en zonas donantes en injertos de piel de espesor parcial

A.4.1

Sponsor's protocol code number

BSG-12

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	Birken AG
B.1.3.4	Country	Germany
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	Birken AG
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Birken AG
B.5.2	Functional name of contact point	Business Unit Pharma
B.5.3	Address:
B.5.3.1	Street Address	Am Hautpbahnhof 10
B.5.3.2	Town/ city	Frankfurt am Main
B.5.3.3	Post code	60329
B.5.3.4	Country	Germany
B.5.4	Telephone number	004972339749115
B.5.5	Fax number	00496990020617
B.5.6	E-mail	k.schuth@birken.eu

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	Oleogel-S10
D.3.4	Pharmaceutical form	Ointment
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Cutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Dry extract from Betulae cortex (Birch cork) (5 - 10:1), quantification: 72 to 88 % Betulin, extraction solvent: n-Heptane 95 % m/m
D.3.9.2	Current sponsor code	TE
D.3.10	Strength
D.3.10.1	Concentration unit	% (W/W) percent weight/weight
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
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	Yes
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

Split-Thickness Skin Graft Donor Sites

zonas donantes en injertos de piel de espesor parcial

E.1.1.1

Medical condition in easily understood language

Wounds resulting from skin areas from which the upper skin layers have been removed in order to be used as skin transplant to cover injuries from the same patient

Heridas en la piel que resultan de la extracción de las capas superiores de la piel con el fin de trasnplantarlas en el propio paciente para cubrir otras lesiones.

E.1.1.2

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

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	10041667
E.1.2	Term	Split thickness skin graft
E.1.2	System Organ Class	100000004865

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To compare intra-individually the efficacy and tolerance of Oleogel-S10 versus standard of care non-adhesive wound dressing alone in accelerating the wound healing of Split-Thickness Skin Graft Donor Sites.

Comparación intraindividual de la eficacia y la tolerancia de Oleogel-S10 frente al tratamiento habitual, tratamiento solo con apósitos no adhesivos, para la aceleración de la cicatrización de las zonas de extracción de injertos de piel de espesor parcial.

E.2.2

Secondary objectives of the trial

not applicable

no aplica

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patients at least 18 years old who have provided written informed consent
Presenting a split-thickness skin graft donor site wound with a minimum size of 20 cm2 and with a minimum width of 3 cm.
Patient is able to understand the ICF provided and is prepared to comply with all study requirements, including the following: Visiting the trial site for wound dressing change and photo documentation every second to third day until both wound halves are closed (but no longer than 28 days after surgery).
Willing to perform all necessary wound dressing changes at the trial site. Also the patient needs to agree to return to site for 3 and 12 months follow-up visits.
Women of childbearing potential who are in the period between menarche and menopause must apply highly effective method of birth control (failure rate less than 1% per year when used consistently and correctly (e.g., implants, injectables, combined oral contraceptives, some intrauterine contraceptive devices (IUDs), sexual abstinence, or a vasectomized partner)). Birth control method must have been applied for at least 1 monthly cycle prior to first administration of study drug, be maintained during the study treatment phase and continued for at least 30 days after the last administration of study drug. Sexually active, non-vasectomized men must use a barrier method (condoms) during the treatment phase of this clinical trial.

Pacientes iguales o mayores de 18 años que han proporcionado su consentimiento informado por escrito.
Herida en la zona de extracción del injerto de piel de espesor parcial de un tamaño mínimo de 20 cm2 y una anchura mínima de 3 cm.
El paciente es capaz de entender el formulario de consentimiento informado proporcionado y está dispuesto a cumplir todos los requisitos del ensayo clínico, incluyendo lo siguiente: Visita al centro del ensayo para el cambio del apósito y la documentación fotográfica cada dos o tres días hasta el cierre de las dos mitades de la herida (pero no más de 28 días desde la intervención quirúrgica).
Disposición a realizar todos los cambios de apósito necesarios en el centro del ensayo. El paciente también debe aceptar volver al centro para las visitas de seguimiento a los tres y a los doce meses.
Las mujeres en edad fértil, aquellas que se encuentran en el período comprendido entre la menarquia y la menopausia deben aplicar un método de alta eficacia en el control de la natalidad (tasa de fracaso inferior al 1% por año cuando se usan sistemática y correctamente (por ejemplo, implantes, inyectables, anticonceptivos orales combinados, algunos dispositivos anticonceptivos intrauterinos (DIU), la abstinencia sexual, o un socio vasectomizado)). El método de control de natalidad deberá haberse aplicado durante al menos 1 ciclo mensual antes de la primera administración del fármaco del estudio, se mantendra durante la fase de tratamiento del estudio y continuará durante al menos 30 días después de la última administración del fármaco del estudio. Los hombres sexualmente activos, no vasectomizados, deben usar un método de barrera (condones) durante la fase de tratamiento de este ensayo clínico.

E.4

Principal exclusion criteria

Diseases or conditions that could, in the opinion of the Investigator, interfere with the assessment of safety or efficacy.
A skin disorder that is chronic or currently active and which the Investigator considers will adversely affect the healing of the acute wounds or involves the areas to be examined in this trial.
A history of clinically significant hypersensitivity to any of the drugs, surgical dressings or excipients to be used in this trial.
Known multiple allergic disorders.
Taking, or have taken, any investigational drugs within 3 months prior to the screening visit.
Pregnant or breast feeding women are not allowed to participate in the study.
Inappropriate to participate in the study, for any reason, in the opinion of the investigator.
Mental incapacity or language barriers precluding adequate understanding the Informed consent form or co-operation or willingness to follow study procedures.
Previous participation in this study.
Employee at the investigational site, relative or spouse of the investigator.

Enfermedades o trastornos que, en opinión del investigador, podrían interferir en la evaluación de la seguridad o la eficacia.
Una enfermedad cutánea crónica o actualmente activa que el investigador considere que afectará de forma negativa a la cicatrización de las heridas o que afecte a las zonas que se deben examinar en este ensayo.
Antecedentes de hipersensibilidad clínicamente significativa a cualquiera de los fármacos, apósitos quirúrgicos o excipientes que se utilizarán en este ensayo.
Trastornos alérgicos múltiples conocidos.
La toma actual o haber tomado fármacos en fase de investigación durante los tres meses previos a la visita de selección.
Las mujeres embarazadas o o en periodo de lactancia no podrán participaren el ensayo clínico.
El paciente no es adecuado para participar en el ensayo clínico por cualquier motivo, según el criterio del investigador.
Incapacidad mental o barreras idiomáticas que impiden la adecuada comprensión del formulario de consentimiento informado o la cooperación o disposición necesarias para cumplir los procedimientos del ensayo clínico.
Haber participado anteriormente en este ensayo clínico.
Ser empleado del centro de investigación, familiar o esposa del investigador.

E.5 End points

E.5.1

Primary end point(s)

Intra-individual difference in time to wound closure (at least 95% epithelialisation) between wound halves either treated with Oleogel-S10 and non-adhesive wound dressing or treated with non-adhesive wound dressing alone (standard of care), based on blinded photo evaluation by three independent, blinded experts.

Diferencia intraindividual del tiempo hasta el cierre de la herida (epitelización de al menos un 95%) entre las mitades de una herida, una de ellas tratada con Oleogel-S10 y un apósito no adhesivo y la otra tratada únicamente con un apósito no adhesivo, tratamiento habitual, basada en una evaluación enmascarada de fotografías por parte de tres expertos independientes que no conocen la medicación administrada. .

E.5.1.1

Timepoint(s) of evaluation of this end point

At every wound dressing change (at least every second or third day until full wound closure is achieved; no longer than 28 days after surgery)

En cada cambio de apósito (por lo menos cada dos o tres días hasta que la herida esté completamente cerrada, no más de 28 días después de la cirugía)

E.5.2

Secondary end point(s)

A) Intra-individual difference in time to wound closure (at least 95% epithelialisation) between wound halves either treated with Oleogel-S10 and non-adhesive wound dressing or treated with non-adhesive wound dressing alone, separately for each of the three independent, blinded experts.
B) Time from surgery until wound closure is achieved, separately for wound halves treated with Oleogel-S10 and non-adhesive wound dressing vs. non-adhesive wound dressing alone.
C) Percentage of patients with earlier healing of wound area treated with Oleogel-S10 compared to non-adhesive wound dressing alone.
D) Percentage of patients with wound closure at different time points.
E) Percentage of wound epithelialization at different time points as assessed by the Investigator.
F) Assessment of efficacy (evaluated by both the investigators and patients).
G) Cosmetic outcome after 3 and 12 months after surgery with regard to texture, redness, growth of hair, and pigmentation, based on blinded photo evaluation.
H) Assessment of tolerance (evaluated by both the investigators and patients).
I) PK data: Systemic presence/concentration of betulin in blood plasma samples.
J) Assessment of adverse events.

A) Diferencia intraindividual del tiempo hasta el cierre de la herida (epitelización de al menos un 95%) entre las mitades de una herida, una de ellas tratada con Oleogel-S10 y un apósito no adhesivo y la otra tratada únicamente con un apósito no adhesivo, de forma separada para cada uno de los tres expertos independientes que no conocen la medicación administrada.
B) Tiempo desde la intervención quirúrgica hasta el cierre de la herida de forma separada para la mitad de la herida tratada con Oleogel-S10 y un apósito no adhesivo frente a la mitad tratada únicamente con un apósito no adhesivo.
C) Porcentaje de pacientes con una cicatrización más temprana de la zona de la herida tratada con Oleogel-S10 que la tratada únicamente con un apósito no adhesivo
D) Porcentaje de pacientes con cierre de la herida en diferentes momentos.
E) Porcentaje de epitelización de la herida en diferentes momentos según la evaluación del investigador
F) Evaluación de la eficacia (efectuada por los investigadores y los pacientes)
G) Resultado estético después de tres y doce meses tras la intervención con respecto a la textura, el enrojecimiento, el crecimiento de pelo y la pigmentación según una evaluación enmascarada de fotografías
H) Evaluación de la tolerancia (efectuada por los investigadores y los pacientes)
I) Datos FC: Presencia/concentración sistémica de betulina en muestras de plasma sanguíneo
J) Evaluación de acontecimientos adversos

E.5.2.1

Timepoint(s) of evaluation of this end point

A) to E), J):
At every wound dressing change (at least every second or third day until full wound closure is achieved; no longer than 28 days after surgery)

F):
Days 7, 14, 21, 28 (each +/- 1 day); only if wound closure did not occur before

G):
3 and 12 months after surgery

H):
Days 7, 14, 21, 28 (each +/- 1 day); only if wound closure did not occur before

I):
Days 7, 14, 21, 28 (each +/- 1 day); only if wound closure did not occur before

de A) a la E), J):

En cada cambio de apósito (por lo menos cada dos o tres días hasta que la herida esté completamente cerrada, no más de 28 días después de la cirugía)

F):

Días 7,14,21,28 (cada +/ - 1 día); solo si la herida no se ha cerrado antes.

G):

3 y 12 meses después de la cirugía

H): Días 7,14,21,28 (cada +/ - 1 día); solo si la herida no se ha cerrado antes.

I): Días 7,14,21,28 (cada +/ - 1 día); solo si la herida no se ha cerrado antes.

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)

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

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Abierto Comparación intraindividual basada en fotoevaluaciónciega por 3 expertos ciegos e independ.

Open Intra-individual comparison based on blinded photoevaluation by 3 independent blinded experts

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

Cura de la herida tratada solamente con cualquier tipo de apósito noadhesivo(práctica clín Habitual)

Wound treatment with any kind of non-adhesive wound dressing only (standard of care)

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

LVLS

LPLV

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.4.2

For a multinational trial

F.4.2.1

In the EEA

130

F.4.2.2

In the whole clinical trial

130

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)

If the patient completes the clinical trial as expected his/her split-thickness skin graft donor site are completly epithelialized. In these cases no further treatment is required.
Upon early discontinuation of the trial for whatever reason, patients will be
treated according to individual needs at the discretion of the
Investigator.

Si el paciente finaliza el ensayo clínico, según lo esperado, su zona donante en injertos de piel de espesor parcial estará totalmente epitelizado. En estos casos no se requerirá ningún otro tratamiento.
En caso de abandono prematuro del ensayo clínico por cualquier razón, los pacientes serán tratados según sus necesidades individuales y a criterio del investigador.

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

2013-02-11

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-01-23

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

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IMP with orphan designation in the indication
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