Clinical Trials Register

Summary
EudraCT Number:	2018-004738-14
Sponsor's Protocol Code Number:	NanoGSkin-CB-2019
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2020-01-10
Trial 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

2018-004738-14

A.3

Full title of the trial

PHASE II CLINICAL TRIAL EVALUATING THE SAFETY AND EFFICACY OF A TISSUE ENGINEERED AUTOLOGOUS SKIN SUBSTITUTE RECONSTRUCTIVE SURGERY FOR BASAL CELL CARCINOMA.

ENSAYO CLINICO FASE II PARA EVALUAR LA SEGURIDAD Y EFICACIA DE UN MODELO DE PIEL AUTÓLOGA CREADA MEDIANTE INGENIERÍA DE TEJIDOS EN LA CIRUGÍA RECONSTRUCTIVA DEL CARCINOMA BASOCELULAR.

A.3.1

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

Study of an artificial human skin medicine for patients with basal cell carcinoma undergoing reconstructive surgery.

Estudio de un medicamento constituido por piel artificial humana en pacientes con carcinoma basocelular que van a someterse a cirugía reconstructiva.

A.4.1

Sponsor's protocol code number

NanoGSkin-CB-2019

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	Red Andaluza de Diseño y Traslación de Terapias Avanzadas - Fundación Pública Andaluza Progreso y Salud
B.1.3.4	Country	Spain
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Instituto de Salud Carlos III - Ministerio de Economía y Competitividad
B.4.2	Country	Spain
B.4.1	Name of organisation providing support	Fundación Pública Andaluza Progreso y Salud - Consejería de Salud y Familias
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	Red Andaluza de Diseño y Traslación de Terapias Avanzadas - Fundación Pública Andaluza Progreso y Salud
B.5.2	Functional name of contact point	Clinical Trial Unit
B.5.3	Address:
B.5.3.1	Street Address	c/ Algodón s/n (Esquina Avda. Hytasa)
B.5.3.2	Town/ city	Seville
B.5.3.3	Post code	41006
B.5.3.4	Country	Spain
B.5.4	Telephone number	+3495504 83 66
B.5.5	Fax number	+3495526 70 02
B.5.6	E-mail	terapias.avanzadas@juntadeandalucia.es

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	Adult autologous skin keratinocytes and fibroblasts expanded on fibrin-hialuronic biological matrix
D.3.2	Product code	NanoGSkin
D.3.4	Pharmaceutical form	Implant
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Cutaneous use Implantation
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	EX-VIVO EXPANDED HUMAN AUTOLOGOUS FIBROBLASTS
D.3.9.3	Other descriptive name	EX-VIVO EXPANDED HUMAN AUTOLOGOUS FIBROBLASTS
D.3.9.4	EV Substance Code	SUB198917
D.3.10	Strength
D.3.10.1	Concentration unit	million CFU million colony forming units
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	1.5 to 3
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	EX-VIVO EXPANDED HUMAN AUTOLOGOUS KERATINOCYTES
D.3.9.3	Other descriptive name	EX-VIVO EXPANDED HUMAN AUTOLOGOUS KERATINOCYTES
D.3.9.4	EV Substance Code	SUB198916
D.3.10	Strength
D.3.10.1	Concentration unit	million CFU million colony forming units
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	1.5 to 3
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)	Yes
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	Yes
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.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	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	Adult autologous skin keratinocytes and fibroblasts expanded on fibrin-agarose biological matrix
D.3.2	Product code	NanoGSkin
D.3.4	Pharmaceutical form	Implant
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Cutaneous use Implantation
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	EX-VIVO EXPANDED HUMAN AUTOLOGOUS FIBROBLASTS
D.3.9.3	Other descriptive name	EX-VIVO EXPANDED HUMAN AUTOLOGOUS FIBROBLASTS
D.3.9.4	EV Substance Code	SUB198917
D.3.10	Strength
D.3.10.1	Concentration unit	million CFU million colony forming units
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	1.5 to 3
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	EX-VIVO EXPANDED HUMAN AUTOLOGOUS KERATINOCYTES
D.3.9.3	Other descriptive name	EX-VIVO EXPANDED HUMAN AUTOLOGOUS KERATINOCYTES
D.3.9.4	EV Substance Code	SUB198916
D.3.10	Strength
D.3.10.1	Concentration unit	million CFU million colony forming units
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	1.5 to 3
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)	Yes
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	Yes
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Reconstructive skin surgery in basal cell cancer (Mohs surgery)

Cirugía reconstructiva de piel en carcinoma basocelular (Cirugía de Mohs)

E.1.1.1

Medical condition in easily understood language

Skin reconstruction surgery in patients with a type of skin cancer that involve basal cells.

Cirugía de reconstrucción de la piel en pacientes con un tipo de cancer de piel que afecta las células basales.

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	20.0
E.1.2	Level	PT
E.1.2	Classification code	10004146
E.1.2	Term	Basal cell carcinoma
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10064974
E.1.2	Term	Mohs micrographic surgery
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

Evaluate the safety and effectiveness of autologous bioengineered skin in reconstructive surgery for basal cell carcinoma (Mohs surgery), in comparison with skin autografts and silicone dressings (Biobrane ®)

Evaluar la seguridad y eficacia de piel autóloga obtenida mediante ingeniería de tejidos en la cirugía reconstructiva del carcinoma basocelular (cirugía de Mohs), en comparación con autoinjertos de piel y apósitos de silicona (Biobrane ®).

E.2.2

Secondary objectives of the trial

- Clinical safety evaluation including any adverse events such as graft detachment, infections, necrosis, or other events.
- Histological evaluation of the skin in the surgical injury.
- Study of cutaneous homeostasis (pH, temperature, transepidermal water loss, elasticity) of the skin in the surgical injury.
- Ultrasound study of the skin in the surgical injury.
- Cost-effectiveness study of terapeutic alternatives evaluated in the trial (autologous skin substitute, autografts and biobrane).

- Evaluación de seguridad analizando los posibles acontecimientos adversos, como el desprendimiento del injerto, la presencia de infecciones, necrosis u otros efectos.
- Evaluación histológica de la lesión quirúrgica.
- Estudio de la homeostasis cutánea (pH, temperatura, pérdida transepidérmica de agua, elasticidad) de la lesión quirúrgica.
- Estudio mediante ecografía de la lesión quirúgica.
- Estudio coste-efectividad de las alternativas de tratamiento evaluadas en el estudio (piel autóloga artificial, autoinjertos y biobrane).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patients that give their informed consent for study participation.
2. Adult (18 years of age or older), of any sex and racial origin.
3. Clinical and dermatoscopic diagnosis of basal cell carcinoma with lesions on the scalp, torso or extremities, within a certain size that do not allow for surgical closure by direct suture or flaps. Namely, indication for Mohs surgery.
4. Women with childbearing age or men capable of producing a child, should commmit to use contraceptives of medically proven efficacy.

1.Firma del consentimiento informado.
2.Pacientes adultos (de 18 años o más), de cualquier sexo y origen racial.
3.Diagnóstico clínico y dermatoscópico de carcinoma basocelular con lesión en cuero cabelludo, tronco o extremidades de un tamaño no permita el cierre quirúrgico mediante sutura directa o colgajo. Indicación de tratamiento mediante cirugía de Mohs.
4.Mujeres en edad fértil u hombres capaces de engendrar un hijo, deben aceptar el compromiso de utilizar métodos anticonceptivos de eficacia médicamente probada.

E.4

Principal exclusion criteria

1. Locally advanced basal cell carcinoma with evidence of tissue infiltration.
2. Lesions in the face.
3. Injuries requiring urgent surgical intervention.
4. Infected lesions, necrosis, scarcely vascularized injuries or other complications that may interfere with healing and/or integrity of the graft.
5. Injuries that have received treatment with radiotherapy.
6. Contraindication for Mohs surgery.
7. Known allergies to Biobrane dressing.
8. Pregnant or breastfeeding women.
9. Coexistence of any other pathology that, in the investigator's opinion, could compromise the healing process or interfere with protocol follow-up.
10. Participation in other clinical trials in 3 months previous to inclusion,
or in the previous 5 years for trials with advanced therapies.

1. Carcinoma basocelular localmente avanzado con evidencias de infiltración de tejidos.
2. Lesiones de localización facial.
3. Lesiones que requieren una intervención quirúrgica urgente.
4. Lesiones infectadas, necrosadas, escasamente vascularizadas u otras complicaciones que puedan condicionar la cicatrización y/o la integridad del injerto.
5. Lesiones que han sido sometidas a tratamiento con radioterapia.
6. Contraindicación para cirugía de Mohs.
7. Alergias conocidas al apósito Biobrane.
8. Embarazo o lactancia.
9. Coexistencia de cualquier otra patología que, a criterio del investigador pueda comprometer el proceso de curación de la lesión o interfiera con el adecuado seguimiento programado en el protocolo.
10. Pacientes que hayan participado en los 3 meses previos a la inclusión en otro ensayo clínico. Este periodo se prolongará hasta 5 años para ensayos clínicos con terapias avanzadas.

E.5 End points

E.5.1

Primary end point(s)

SAFETY ENDPOINTS: adverse events, including complications and sequelae in the healing of the surgical injury, as well as the severity of pain (analogical visual scale and use of analgesics). Both the surgical injury and the donor area (when applicable) will be taken into account in the evaluation.
EFFICACY ENDPOINTS: clínical progress and time to complete epithelialization of the injury, time to removal of the suture, aesthetic quality of the lesion (POSAS questionnaire) and quality of life (DLQI). Efficacy variables will be measured both in the surgical lesion as well as in the donor area (when applicable).

VARIABLES DE SEGURIDAD: acontecimientos adversos, incluidas las complicaciones y secuelas en la cicatrización de la lesión quirúrgica, así como la severidad del dolor (escala visual analógica y uso de analgésicos). En la evaluación se tendrá en cuenta tanto la lesión quirúrgica como la zona donante (cuando aplique).
VARIABLES DE EFICACIA: evolución y tiempo hasta la completa epitelización de la lesión, tiempo hasta la retirada de la sutura, calidad estética de la lesión (cuestionario POSAS) y calidad de vida (DLQI). Las variables de eficacia se medirán tanto en la lesión quirúrgica como en la zona donante (cuando aplique).

E.5.1.1

Timepoint(s) of evaluation of this end point

At baseline and at day 5, 12, 30, 60, 90, 150, 210, 365, 548 and 730 after surgery, acording to the visits and assessments schedule of the trial protocol.

Al inicio y a los 5, 12, 30, 60, 90, 150, 210, 365, 548 y 730 días tras la cirugía, conforme al calendario de visitas e evaluaciones del protocolo del estudio.

E.5.2

Secondary end point(s)

Complementarily, a set of structural characteristics, molecular and functional properties of the skin will be measured in the surgical injury using different study techniques: doppler ultrasound, cutaneous homeostasis study, histological tests of skin biopsies using optical microscopy and immunohistochemical analysis.

Complementariamente se medirán un conjunto de características estructurales, propiedades moleculares y funcionales de la piel en la lesión quirúrgica aplicando diferentes técnicas de estudio: ecografía doppler, estudio de homeostasis cutánea, estudio histológico de biopsias de piel mediante microscopía y análisis inmunohistoquímico.

E.5.2.1

Timepoint(s) of evaluation of this end point

At baseline and at day 5, 12, 30, 60, 90, 150, 210, 365, 548 and 730 after surgery, acording to the visits and assessments schedule of the trial protocol.

Al inicio y a los 5, 12, 30, 60, 90, 150, 210, 365, 548 y 730 días tras la cirugía, conforme al calendario de visitas e evaluaciones del protocolo del 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

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

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

Autoinjerto de piel (intervención quirúrgica)

Skin autografts (surgical intervention) / Biobrane (Medical device)

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

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

Last visit of the last patient included

Última visita del último paciente incluido

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

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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)

No planned post trial treatment, as surgical injury is expected resolve without sequeale throughout trial follow-up.

No se planifica ningún tratamiento post estudio, se espera que la lesión quirúrgica se resuelva sin secuelas durante el seguimiento.

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

2020-04-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-04-27

P. End of Trial
P.	End of Trial Status	Ongoing

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