Clinical Trials Register

Summary
EudraCT Number:	2017-002462-41
Sponsor's Protocol Code Number:	TBRU-dS-RAC-PII
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2018-04-17
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

Netherlands - Competent Authority

A.2

EudraCT number

2017-002462-41

A.3

Full title of the trial

A Phase II, prospective, intra-patient randomized controlled, multicentre study to evaluate the safety and efficacy of an autologous bio-engineered dermo-epidermal skin substitute (EHSG-KF) for the treatment of full thickness skin defects in adults and children in comparison to autologous split-thickness skin grafts (STSG)

A.3.1

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

A study performed in more hospitals, to assess the safety and efficacy of a skin model that is engineered in the lab with cells of the patient (EHSG-KF) to use in treatment of full thickness burns in adults and children and compare this to the treatment with the own skin system called STSG.

A.4.1

Sponsor's protocol code number

TBRU-dS-RAC-PII

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT03394612

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/364/2020

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	CUTISS 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	Wyss Zurich
B.4.2	Country	Switzerland
B.4.1	Name of organisation providing support	Cutiss AG
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	CUTISS AG
B.5.2	Functional name of contact point	F. Hartmann
B.5.3	Address:
B.5.3.1	Street Address	Grabenstrasse 11
B.5.3.2	Town/ city	Schlieren
B.5.3.3	Post code	8952
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	+41 44244 36 60
B.5.6	E-mail	info@cutiss.swiss

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	Yes
D.2.5.1	Orphan drug designation number	EU/3/15/1596
D.3 Description of the IMP
D.3.1	Product name	EHSG-KF
D.3.2	Product code	EHSG-KF
D.3.4	Pharmaceutical form	Cutaneous patch
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	Autogolous Skin Cells
D.3.9.1	CAS number	na
D.3.9.2	Current sponsor code	na
D.3.9.3	Other descriptive name	Human Autologous Skin Cells
D.3.10	Strength
D.3.10.1	Concentration unit	Other
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	1 to 10000000
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)	No
	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	Yes
D.3.11.3.5.1	CAT classification and reference number	H0004817
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

Adults and children with full thickness skin defects

E.1.1.1

Medical condition in easily understood language

Adults and children with full thickness skin wounds

E.1.1.2

Therapeutic area

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

MedDRA Classification

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 evaluate the efficacy and safety of EHSG-KF in comparison to STSG
(unmeshed or meshed up to 1:3) in adults and children with
large full-thickness skin defects.
Primary Objective:
To evaluate the efficacy of EHSG-KF in comparison to STSG based on
the assessment of:
• Scar quality:
o POSAS questionnaire, observer total score 3 months
post grafting

E.2.2

Secondary objectives of the trial

Secondary Objectives
To evaluate the safety and efficacy of EHSG-KF in comparison to STSG
(unmeshed or meshed up to 1:3) based on the assessment of:
• Scar quality:
o Cutometer® 3 months post grafting
o POSAS questionnaire, observer items 3 months post
grafting
o POSAS questionnaire, patient items and total score 3
months post grafting
o DSM ColorMeter® (1 year post
grafting)
o Optional biopsies of the study area and control area (1 year post grafting) for histological
assessment. (optional)
• Infection 6-10 days and 3 weeks post grafting
• Graft take at 6-10 days post grafting
• % Epithelialization at 4 weeks post grafting
• Adverse events
• QOL assessment (1 year) post grafting
o EQ-5D and BSHS-B for patients ≥ 18 with reconstruction of
burn scars,
o EQ-5D only for patients ≥18 years without burn scars
o EQ-5DY and PedsQL for patients <18 years
• Ratio of covered surface area to biopsy site/donor site surface
area 4 weeks post grafting

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Age: ≥1 year of age
• Large full-thickness defects that require coverage after excision
of:
o Scars
o Benign skin tumors (e.g. neurofibroma)
o Melanocytic nevus (e.g. giant nevus)
o Gender reassignment surgery
o Soft tissue defect after trauma
o Soft tissue defect after infection and debridement (e.g.
necrotizing fascitis, hidradentitis suppurativa, purpura
fulminans)
o Flap donor site (e.g. radial forearm flap)
• Minimal areas requiring coverage (not counting the head and neck
area for study patients in The Netherlands):
o Minimum: 1-5 years: 9 cm2
o Minimum: 6-16 years: 25 cm2
o Minimum: > 16 years: 45 cm2
• Signed informed consent from the patient or the
parents/legally authorized representative.

E.4

Principal exclusion criteria

• Patients tested positive for HBV, HCV, syphilis or HIV
• Patients with known underlying or concomitant medical conditions that may interfere with normal wound healing (e.g. systemic skin and connective tissue diseases, any kind of congenital defect of metabolism including insulin-dependent diabetes mellitus, Cushing syndrome or disease, scurvy, chronic hypothyroidism, congenital or acquired immunosuppressive condition, chronic renal failure, or chronic hepatic dysfunction (Child-Pugh class B or C), severe malnutrition, or other concomitant illness which, in the opinion of the Investigator, has the potential to significantly delay wound healing)
• Severe drug and alcohol abuse
• Pre-existing coagulation disorders as defined by INR outside its normal value, PTT >ULN and fibrinogen <LLN prior to the current hospital admission and / or at the Investigator’s discretion
• Patients with known allergies to amphotericin B, gentamicin,
penicillin, streptomycin, or bovine collagen
• Previous enrolment of the patient into the current phase II study
• Participation of the patient in another study with conflicting endpoints within 30 days preceding and during the present study
• Patients or or parents/legally authorized representative expected not to comply with the study protocol (including patients with severe cognitive dysfunction/impairment and severe psychiatric disorders)
• Pregnant or breast feeding females
• Intention to become pregnant during the clinical course of the study (12 months)
• Wounds in the head and neck area as study target area (only
applicable for study patients in The Netherlands)
• Enrolment of the Investigator, his/her family members, employees and other dependent persons

E.5 End points

E.5.1

Primary end point(s)

Primary Endpoint
Efficacy evaluation, as a comparison between the EHSG-KF and control
sites, based on assessment of general scar quality at the study areas using
the POSAS questionnaire, observer total score at: visit 8 (90 days ±5
days post grafting)

E.5.1.1

Timepoint(s) of evaluation of this end point

At visit 8

E.5.2

Secondary end point(s)

Secondary Endpoints
Efficacy evaluation, as a comparison between the EHSG-KF and control sites, based on:
• Scar quality at the study areas in comparison to control areas:
o Cutometer® pliability parameter at visit 8 (90 days ±5 days post grafting) as key secondary efficacy endpoint
o Other Cutometer® parameters (extension, elasticity, retraction, viscoelasticity) at visit 8 (90 days ±5 days post
grafting)
o POSAS questionnaire observer items (vascularity, pigmentation, thickness, relief, pliability) at visit 8 (90 days ±5 days post grafting)
o POSAS questionnaire patient items (pain, itching, colour, pliability, thickness, relief) and total score at visit 8 (90
days ±5 days after grafting)
o DSM ColorMeter® (erythema and pigmentation) at: visit 10 (1 year ±30 days post grafting)
o Optional biopsies of the study area and control area at visit 10 (1 year ±30 days after grafting) for histological
assessment. (optional)
o Graft take at Visit 4 (6-10 days after grafting)
o % Epithelialization at Visit 6 (28 days ± 3 days after grafting)
Secondary safety endpoints:
• Clinical and microbiologic signs of infection at
o visits 4 (6-10 days post grafting)
o visit 5 (21 ±2 days post grafting)
• Adverse events
o Assessment and reporting of all observed adverse events will be carried for the full duration of the study from visit 2 on.
Other secondary efficacy endpoint:
• QOL assessment: visit 10 (1 year ±30 days post grafting)
o EQ-5D and BSHS-B for patients ≥18 years with reconstruction of a burn scar
o EQ-5D only for patients ≥18 years without burn scars
o EQ-5DY and PedsQL for patients <18 years

E.5.2.1

Timepoint(s) of evaluation of this end point

At visit 4, 5, 6, 8, 10

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

Yes

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

Yes

E.8.1.7.1

Other trial design description

intra-patient randomised controlled

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

autologous split-thickness skin

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

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

Switzerland

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

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

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)

Yes

F.1.1.5.1

Number of subjects for this age range:

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)

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Children till 12 years

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

2018-02-01

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-10-29

P. End of Trial
P.	End of Trial Status	Trial now transitioned

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