A multicentre, intra-patient randomised controlled Phase III study to confirm the efficacy and safety of denovoSkin™, a bilayer engineered collagen-based skin graft composed of autologous fibroblasts and keratinocytes, for the treatment of patients with deep partial and full-thickness burns

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Cutiss AG

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

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

Trial duration

6 Dec 2024 → ongoing

Decision date (initial)

2024-07-29

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Cutiss AG

External identifiers

EU CT number

2023-507717-94-00

WHO UTN

U1111-1298-4686

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To confirm the efficacy and functionality of denovoSkin™ in achieving wound closure and reducing scarring in patients with deep partial and full-thickness burns as compared to STSG

Secondary objectives 2

1. First Secondary Objectives: • To confirm the donor-site sparring effect of denovoSkin™ by comparing the difference of the expansion ratio between the IMP and STSG • To confirm the limitation of scar contracture by comparing the size of the area grafted with IMP and STSG over time
2. Other Secondary Objective: • To confirm the progression and quality of the burn wound and donor site wound healing after denovoSkin™ grafting as compared to meshed STSG

Conditions and MedDRA coding

Deep partial and full-thickness burns

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-002699-PIP01-19

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. 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
2. 2. Patients of either sex aged ≥12 years
3. 3. Signed informed consent from the patient and/or legally authorised representative

Exclusion criteria 12

1. 1. Burn wound areas solely located on the head and neck (i.e., test and control areas must NOT be located on head/neck)
2. 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
3. 12. Patient is the Investigator, one of his/her family members, employees, and other dependent persons
4. 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
5. 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
6. 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
7. 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)
8. 7. Previous treatment with denovoSkin™
9. 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
10. 9. Patients unwilling or unable to comply with procedures required in this clinical study protocol
11. 10. Pregnant or lactating women
12. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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

Secondary endpoints 4

1. 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
2. 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)
3. 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.
4. Other Secondary Endpoints: Limitation of scar contracture by assessing the size of the grafted areas at 12 and 24 months post-grafting

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Cutiss AG

Sponsor organisation

Cutiss AG

Address

Grabenstrasse 11

City

Schlieren

Postcode

8952

Country

Switzerland

Scientific contact point

Organisation

Cutiss AG

Contact name

Clinical Trial Management

Public contact point

Organisation

Cutiss AG

Contact name

Clinical Trial Management

Third parties 3

Locations

8 EU/EEA countries · 23 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 123 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications