Clinical trial • Phase III • Dermatology | Rare Disease

BILAYER ENGINEERED COLLAGEN HYDROGEL-BASED SKIN GRAFT COMPOSED OF AUTOLOGOUS KERATINOCYTES AND FIBROBLASTS for Deep partial-thickness and full-thickness burns

Phase III trial of BILAYER ENGINEERED COLLAGEN HYDROGEL-BASED SKIN GRAFT COMPOSED OF AUTOLOGOUS KERATINOCYTES AND FIBROBLASTS for Deep partial-thickness a…

Overview

Trial Therapeutic Area
Dermatology | Rare Disease
Trial Disease
Deep partial-thickness and full-thickness burns
Trial Stage
Phase III
Drug Modality
Cell therapy
Paediatric Trial
Yes
Orphan Drug
Yes

Key dates

Initial CTIS Submission Date
28-03-2024
First CTIS Authorization Date
22-07-2024

Trial design

Randomised, open-label, autologous split thickness skin grafts (stsg) — intra-patient comparator (standard of care), no drug dose/schedule applicable-controlled Phase III trial in Belgium, Italy, Portugal and others.

Randomised
Yes
Open Label
Yes
Comparator
Autologous split thickness skin grafts (STSG) — intra-patient comparator (standard of care), no drug dose/schedule applicable
Target Sample Size
98
Trial Duration For Participant
730

Eligibility

Recruits 98 paediatric patients.

Pregnancy Exclusion
10. Pregnant or lactating women
Vulnerable Population
Vulnerable population selected. Participants include adolescents aged ≥12 years. Signed informed consent is required from the patient and/or a legally authorised representative. Study documents include age-specific subject information sheets and informed consent forms for children/adolescents (e.g., Child 12-15 yr, Child 16-18 yr), and parents/legal representative forms; materials are provided in multiple country/language versions (examples in the dossier include EN, FR, DE, NL, IT, PT, ES, PL).

Inclusion criteria

  • {"criterion_text":"- 1. Patients with deep partial or full-thickness thermal burns of >20% TBSA for which excision and SOC (STSG) are clinically indicated according to the applicable ISBI Practice Guidelines for Burn Care"}
  • {"criterion_text":"- 2. Patients of either sex aged ≥12 years"}
  • {"criterion_text":"- 3. Signed informed consent from the patient and/or legally authorised representative"}

Exclusion criteria

  • {"criterion_text":"- 1. Burn wound areas solely located on the head and neck (i.e., test and control areas must NOT be located on head/neck)"}
  • {"criterion_text":"- 9. Patients unwilling or unable to comply with procedures required in this clinical study protocol"}
  • {"criterion_text":"- 10. Pregnant or lactating women"}
  • {"criterion_text":"- 2. Patients eligible to have all areas autografted in a single surgery or significantly earlier than the end of the manufacturing period of denovoSkin™, for whom the application of denovoSkin™ would delay the standard of care therapies"}
  • {"criterion_text":"- 11. Women of child-bearing potential not using highly effective method(s) of birth control (i.e., with low failure rate <1% per year) throughout the study and/or unwilling to be tested for pregnancy. A negative serum beta-human chorionic gonadotropin (β-hCG) test is required on the day of grafting"}
  • {"criterion_text":"- 12. Patient is the Investigator, one of his/her family members, employees, and other dependent persons"}
  • {"criterion_text":"- 3. Patients with serologic evidence of active hepatitis B virus infection (i.e., positive for Hepatitis B surface antigen or immunoglobulin M total Hepatitis B core antibody), active hepatitis C infection (hepatitis C virus antibody positive),positive human immunodeficiency virus serology, or positive Treponema pallidum serology"}
  • {"criterion_text":"- 4. Patients with known underlying or concomitant medical conditions that, in the opinion of the Investigator, has the potential to significantly delay wound healing, e.g., glycated haemoglobin (HbA1c) ≥53 mmol/mol and/or systemic skin and connective tissue diseases"}
  • {"criterion_text":"- 5. Patients with pre-existing coagulation disorders as defined by international normalised ratio outside its normal value, a prothrombin time greater than the upper limit of normal, and fibrinogen less than the lower limit of normal prior to the current hospital admission"}
  • {"criterion_text":"- 6. Patients with a history of clinically significant hypersensitivity/allergy to amphotericin B, gentamicin, penicillin, streptomycin, or bovine collagen and it’s derivatives (e.g. gelatine) and bovine proteins such as Fetal Calf Serum (FBS)"}
  • {"criterion_text":"- 7. Previous treatment with denovoSkin™"}
  • {"criterion_text":"- 8. Patients treated <60 days with monoclonal antibodies, and <30 days with any other IMP or skin-cell related therapy, prior to screening visit for the denovoSkin™ study"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- A composite endpoint whereby success is defined by meeting both of the following criteria: • Wound closure defined as at least 95% epithelialisation at 10 weeks post-grafting • POSAS v2.0 overall opinion of at most 5, based on the observer evaluation (observer part of POSAS) at 6 months post-grafting","definition_or_measurement_approach":"Success requires both: Wound closure defined as at least 95% epithelialisation at 10 weeks post-grafting; and POSAS v2.0 overall opinion ≤ 5 based on the observer evaluation at 6 months post-grafting."}

Secondary endpoints

  • {"endpoint_text":"- First Secondary Endpoints: • Ratio of covered surface area to biopsy site/donor site surface area at 4 weeks post-grafting • Limitation of scar contracture by assessing the size of the grafted areas at 6 months as compared to the grafting visit","definition_or_measurement_approach":"Measurement of ratio of covered surface area to biopsy site/donor site surface area at 4 weeks; assessment of grafted area size at 6 months compared to grafting visit to evaluate scar contracture limitation."}
  • {"endpoint_text":"- Other Secondary Endpoints: • Epithelialisation percentage at 3 months and 6 months post-grafting • Graft take at 14 and 21 days post-grafting • Assessment of the donor sites (i.e., biopsies for IMP manufacturing and STSG grafting) at 4 and 10 weeks and 3, 6, 12, and 24 months post-grafting for: • Infection • Scar quality (patient and observer assessment using the POSAS v2.0 questionnaire)","definition_or_measurement_approach":"Epithelialisation percentage measured at 3 and 6 months; graft take assessed at days 14 and 21; donor site assessments at listed timepoints for infection and scar quality using patient and observer POSAS v2.0 questionnaires."}
  • {"endpoint_text":"- Other Secondary Endpoints: Assessment of the grafted burn wounds areas (i.e., experimental and control areas) at 4 and 10 weeks and 3, 6, 12, and 24 months post-grafting for: • Infection • Scar quality (patient and observer assessment using the POSAS v2.0 questionnaire). Note: Observer assessment using POSAS at 6 months is part of the composite primary endpoint.","definition_or_measurement_approach":"Assessment of experimental and control grafted burn wound areas at specified timepoints for infection and scar quality using POSAS v2.0; observer POSAS at 6 months is included in primary composite."}
  • {"endpoint_text":"- Other Secondary Endpoints: Limitation of scar contracture by assessing the size of the grafted areas at 12 and 24 months post-grafting","definition_or_measurement_approach":"Assessment of size of grafted areas at 12 and 24 months post-grafting to evaluate limitation of scar contracture over long-term follow-up."}

Recruitment

Planned Sample Size
98
Recruitment Window Months
41
Consent Approach
Signed informed consent required from the patient and/or legally authorised representative. Age-specific subject information sheets and ICFs are provided for adolescents (e.g., Child 12-15 yr, Child 16-18 yr), adults, and for parents/legal representatives. Materials and consent documents are provided in multiple languages appropriate to participating countries (examples in dossier: EN, FR, DE, NL, IT, PT, ES, PL).

Geography

Total Number Of Sites
22
Total Number Of Participants
98

Belgium

Earliest CTIS Part Ii Submission Date
24-06-2024
Latest Decision Or Authorization Date
29-07-2024
Processing Time Days
35
Number Of Sites
2
Number Of Participants
10

Sites

Site Name
Centre hospitalier universitaire de Liege
Department Name
Plastic Surgery Unit
Principal Investigator Name
François MARTIN
Principal Investigator Email
francois.martin@chuliege.be
Contact Person Name
François MARTIN
Contact Person Email
francois.martin@chuliege.be
Site Name
Queen Astrid Military Hospital
Department Name
Burn Unit
Principal Investigator Name
Thomas ROSE
Principal Investigator Email
thomas.rose@mil.be
Contact Person Name
Thomas ROSE
Contact Person Email
thomas.rose@mil.be

Italy

Earliest CTIS Part Ii Submission Date
24-06-2024
Latest Decision Or Authorization Date
24-07-2024
Processing Time Days
30
Number Of Sites
3
Number Of Participants
10

Sites

Site Name
Azienda Ospedale-Universita Padova
Department Name
Plastic Surgery Unit
Principal Investigator Name
Franco BASSETTO
Principal Investigator Email
franco.bassetto@unipd.it
Contact Person Name
Franco BASSETTO
Contact Person Email
franco.bassetto@unipd.it
Site Name
L’Azienda Ospedaliera Di Rilievo Nazionale Santobono-Pausilipon
Department Name
Department of Paediatric Surgery – Plastic Surgery and Burns Unit
Principal Investigator Name
Marcello ZAMPARELLI
Principal Investigator Email
m.zamparelli@santobonopausilipon.it
Contact Person Name
Marcello ZAMPARELLI
Site Name
Azienda Ospedaliera Di Rilievo Nazionale Antonio Cardarelli
Department Name
Plastic Surgery and Major Burn Center
Principal Investigator Name
Ilaria MATARO
Principal Investigator Email
ilaria.mataro@aocardarelli.it
Contact Person Name
Ilaria MATARO
Contact Person Email
ilaria.mataro@aocardarelli.it

Portugal

Earliest CTIS Part Ii Submission Date
30-06-2024
Latest Decision Or Authorization Date
22-07-2024
Processing Time Days
22
Number Of Sites
1
Number Of Participants
5

Sites

Site Name
Centro Hospitalar E Universitario De Coimbra E.P.E.
Department Name
Plastic Surgery and Burns Unit
Principal Investigator Name
Luís CABRAL
Principal Investigator Email
secqueim@chuc.min-saude.pt
Contact Person Name
Luís CABRAL
Contact Person Email
secqueim@chuc.min-saude.pt

Spain

Earliest CTIS Part Ii Submission Date
01-07-2024
Latest Decision Or Authorization Date
24-07-2024
Processing Time Days
23
Number Of Sites
3
Number Of Participants
10

Sites

Site Name
Hospital Universitari Vall D Hebron
Department Name
Plastic Surgery
Principal Investigator Name
Jordi SERRACANTA DOMENECH
Principal Investigator Email
Jordi.serracanta@vallhebron.cat
Contact Person Name
Jordi SERRACANTA DOMENECH
Site Name
Hospital Universitario La Paz
Department Name
Plastic Surgery Department
Principal Investigator Name
Jose Ramón MARTINEZ MENDEZ
Principal Investigator Email
Josermartinez77@gmail.com
Contact Person Name
Jose Ramón MARTINEZ MENDEZ
Contact Person Email
Josermartinez77@gmail.com
Site Name
Hospital Universitario Y Politecnico La Fe
Department Name
Plastic, Aesthetic and Reconstructive Surgeon
Principal Investigator Name
María Dolores PEREZ DEL CAZ
Principal Investigator Email
draperezdelcaz@gmail.com
Contact Person Name
María Dolores PEREZ DEL CAZ
Contact Person Email
draperezdelcaz@gmail.com

Poland

Earliest CTIS Part Ii Submission Date
01-07-2024
Latest Decision Or Authorization Date
29-07-2024
Processing Time Days
28
Number Of Sites
1
Number Of Participants
5

Sites

Site Name
Samodzielny Publiczny Zaklad Opieki Zdrowotnej W Lecznej
Department Name
Klinika Chirurgii Plastycznej, Rekonstrukcyjnej i Leczenia Oparzeń
Principal Investigator Name
Tomasz KORZENIOWSKI
Principal Investigator Email
t.korzeniowski@gmail.com
Contact Person Name
Tomasz KORZENIOWSKI
Contact Person Email
t.korzeniowski@gmail.com

Germany

Earliest CTIS Part Ii Submission Date
01-07-2024
Latest Decision Or Authorization Date
26-07-2024
Processing Time Days
25
Number Of Sites
6
Number Of Participants
13

Sites

Site Name
BG Kliniken Ludwigshafen und Tuebingen gGmbH
Department Name
Klinik für Hand-, Plastische- und Rekonstruktive Chirurgie, Mikrochirurgie, Schwerbrandverletzten
Principal Investigator Name
Gabriel HUNDESHAGEN
Principal Investigator Email
gabriel.hundeshagen@bgu-ludwigshafen.de
Contact Person Name
Gabriel HUNDESHAGEN
Site Name
BG Klinikum Unfallkrankenhaus Berlin gGmbH
Department Name
Zentrum für Schwerbrandverletzte mit Plasticscher Chirurgie
Principal Investigator Name
Martin Aman
Principal Investigator Email
Martin.Aman@ukb.de
Contact Person Name
Martin Aman
Contact Person Email
Martin.Aman@ukb.de
Site Name
BG Unfallklinik Murnau gGmbH
Department Name
Department of Plastic, Aesthetic and Reconstruction microsurgery - Burn Unit
Principal Investigator Name
Britta WALLNER
Principal Investigator Email
Britta.Wallner@bgu-murnau.de
Contact Person Name
Britta WALLNER
Contact Person Email
Britta.Wallner@bgu-murnau.de
Site Name
Medizinische Hochschule Hannover
Department Name
Department of Plastic, Hand and Reconstructive Surgery – Burn Center
Principal Investigator Name
Anieto ENECHUKWU
Principal Investigator Email
enechukwu.anieto@mh-hannover.de
Contact Person Name
Anieto ENECHUKWU
Site Name
Berufsgenossenschaftliches Universitaetsklinikum Bergmannsheil gGmbH
Department Name
Universitätsklinik Plastische Chirurgie und Handchirurgie
Principal Investigator Name
Christoph WALLNER
Principal Investigator Email
christoph.wallner@bergmannsheil.de
Contact Person Name
Christoph WALLNER
Site Name
BG Klinikum Bergmannstrost Halle gGmbH
Department Name
Plastic and Hand Surgery, Burn lnjury Center
Principal Investigator Name
Frank SIEMERS
Principal Investigator Email
siemers@bergmannstrost.de
Contact Person Name
Frank SIEMERS
Contact Person Email
siemers@bergmannstrost.de

France

Earliest CTIS Part Ii Submission Date
05-07-2024
Latest Decision Or Authorization Date
29-07-2024
Processing Time Days
24
Number Of Sites
3
Number Of Participants
35

Sites

Site Name
Hospital Edouard Herriot
Department Name
Centre des Grands Brulés
Principal Investigator Name
Maria SERBU
Principal Investigator Email
maria.serbu@chu-lyon.fr
Contact Person Name
Maria SERBU
Contact Person Email
maria.serbu@chu-lyon.fr
Site Name
Centre Hospitalier Universitaire De Nantes
Department Name
Plastic Surgery
Principal Investigator Name
Pierre Perrot
Principal Investigator Email
pierre.perrot@chunantes.fr
Contact Person Name
Pierre Perrot
Contact Person Email
pierre.perrot@chunantes.fr
Site Name
Centre Hospitalier Universitaire De Montpellier
Department Name
Chirurgie Plastique, Reconstructrice et esthétique - Brulés
Principal Investigator Name
Christian HERLIN
Principal Investigator Email
c-herlin@chu-montpellier.fr
Contact Person Name
Christian HERLIN
Contact Person Email
c-herlin@chu-montpellier.fr

Netherlands

Earliest CTIS Part Ii Submission Date
24-06-2024
Latest Decision Or Authorization Date
22-07-2024
Processing Time Days
28
Number Of Sites
3
Number Of Participants
10

Sites

Site Name
Maasstad Ziekenhuis Stichting
Department Name
Burn Centre and Department of Surgery
Principal Investigator Name
Cornelis Hendrik VAN DER VLIES
Principal Investigator Email
VliesC@maasstadziekenhuis.nl
Contact Person Name
Cornelis Hendrik VAN DER VLIES
Contact Person Email
VliesC@maasstadziekenhuis.nl
Site Name
Rode Kruis Ziekenhuis B.V.
Department Name
Burn Centrer
Principal Investigator Name
Anouk PIJPE
Principal Investigator Email
apijpe@rkz.nl
Contact Person Name
Anouk PIJPE
Contact Person Email
apijpe@rkz.nl
Site Name
Stichting Martini Ziekenhuis
Department Name
Brandwondencentrum Groningen
Principal Investigator Name
Eelke BOSMA
Principal Investigator Email
Eelke.Bosma@mzh.nl
Contact Person Name
Eelke BOSMA
Contact Person Email
Eelke.Bosma@mzh.nl

Sponsor

Primary sponsor

Full Name
Cutiss AG
Organisation Type
Pharmaceutical company
Country Of Registered Address
Switzerland

Contract research organisations

Name
PPD Development Ireland Limited
Responsibilities
manufacturing authorisation and medicinal product importation
Name
RCTS Randomized Clinical Trials
Responsibilities
sponsor duties codes: [1,10,11,13,2,3,5,6,7,8,9] (as listed in dossier)

Third parties

  • {"country":"France","full_name":"RCTS Randomized Clinical Trials","duties_or_roles":"[1,10,11,13,2,3,5,6,7,8,9]","organisation_type":"Pharmaceutical company"}
  • {"country":"France","full_name":"Pharmalex France","duties_or_roles":"[11,12]","organisation_type":"Pharmaceutical company"}
  • {"country":"Ireland","full_name":"PPD Development Ireland Limited","duties_or_roles":"manufacturing authorisation and medicinal product importation","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
EHSG-KF
Active Substance
BILAYER ENGINEERED COLLAGEN HYDROGEL-BASED SKIN GRAFT COMPOSED OF AUTOLOGOUS KERATINOCYTES AND FIBROBLASTS
Modality
Cell therapy
Routes Of Administration
IMPLANTATION
Route
IMPLANTATION
Orphan Designation
Yes
Maximum Dose
336 cm2

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