Phase III Study with an Autologous Dermo-epidermal Skin Substitute for the Treatment of Burns in Adults and Adolescents

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

This multicentre phase III clinical trial will target adults and adolescents of 12 years and older with severe burns 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 split-thickness skin.

Study Overview

• Status: Recruiting
• Conditions: Burns
• Intervention / Treatment: Biological: denovoSkin(TM); Other: STSG

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Daniela Marino; Phone Number: +41 44 244 36 60; Email: clinicaltrials@cutiss.swiss

Study Locations

• Netherlands
  • Beverwijk, Netherlands, 1942
    • Recruiting
    • Rode Kruis Ziekenhuis
    • Contact: Prof. E. Middelkoop; Phone Number: +31 251 265 555; Email: emiddelkoop@burns.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with deep partial or full-thickness thermal burns of ≥20% total body surface area (TBSA) for which excision and standard of care (SOC) (STSG) are clinically indicated
• Patients of either sex aged ≥12 years
• Signed informed consent from the patient and/or legally authorised representative

Exclusion Criteria:

• Burn wound areas solely located on the head and neck (i.e., test and control areas must NOT be located on head/neck)
• 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
• Patients with serologic evidence of active hepatitis B virus (HBV) infection (i.e., positive for Hepatitis B surface antigen [HbsAg] or immunoglobulin M total hepatitis B core antibody [anti-HBc]), active hepatitis C infection (hepatitis C virus [HCV] antibody positive), positive human immunodeficiency virus (HIV) serology, or positive Treponema pallidum serology assessed as per local standard of care; cured hepatitis C (defined as documented treatment and negative viral load) is not an exclusion
• 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
• Patients with pre-existing coagulation disorders as defined by international normalised ratio (INR) outside its normal value, a prothrombin time (PT) greater than the upper limit of normal, and fibrinogen less than the lower limit of normal prior to the current hospital admission
• Patients with a history of clinically significant hypersensitivity to amphotericin B, gentamicin, penicillin, streptomycin, or bovine collagen and it's derivatives (e.g. gelatine)
• Previous treatment with denovoSkin™
• Participation in any clinical interventional study within 60 days prior to the first IMP administration in case of monoclonal antibodies and <30 days for all other IMPs
• Patients unwilling or unable to comply with procedures required in this clinical study protocol
• Pregnant or lactating women
• 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
• Patient is the Investigator, one of his/her family members, employees, and other dependent persons

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Option 1; Location A is the experimental area and Location B is the control area	Biological: denovoSkin(TM); Transplantation of autologous dermo-epidermal skin substitute denovoSkin(TM) to the experimental area; Other Names: EHSG-KF; Other: STSG; Transplantation of autologous split-thickness skin to the control area; Other Names: split-thickness skin graft
Other: Option 2; Location A is the control area and Location B is the experimental area	Biological: denovoSkin(TM); Transplantation of autologous dermo-epidermal skin substitute denovoSkin(TM) to the experimental area; Other Names: EHSG-KF; Other: STSG; Transplantation of autologous split-thickness skin to the control area; Other Names: split-thickness skin graft

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
A composite endpoint whereby success is defined by meeting both of the following criteria: - Wound closure - Scar quality (POSAS v2.0)	A composite endpoint whereby success is defined by meeting both of the following criteria: Wound closure; Scar quality (POSAS v2.0)	6 months post grafting

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ratio of covered surface area to biopsy site/donor site surface area at 4 weeks post-grafting	Ratio of covered surface area to biopsy site/donor site surface area at 4 weeks post-grafting	4 weeks
Assessment of scar contracture	Assessment of scar contracture	6 months post grafting
Epithelialisation percentage at 3 months and 6 months post-grafting	Epithelialisation percentage at 3 months and 6 months post-grafting	3 months and 6 months post-grafting
Graft take at 14 and 21 days post-grafting	Graft take at 14 and 21 days post-grafting	14 and 21 days post-grafting
Assessment of the donor sites	Assessment of the donor sites	4 and 10 weeks, and 3, 6, 12, and 24 months post-grafting
Assessment of the grafted burn wounds areas	Assessment of the grafted burn wounds areas	4 and 10 weeks and 3, 6, 12, and 24 months post-grafting
Assessment of scar contracture	Assessment of scar contracture	12 and 24 months post-grafting

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of safety and tolerability using the National Cancer Institute-CTCAE v5.0 throughout the study: - Assessment of the incidence of treatment-emergent adverse events (TEAEs), total AEs, and serious adverse events (SAEs)	Assessment of safety and tolerability using the National Cancer Institute-CTCAE v5.0 throughout the study: - Assessment of the incidence of treatment-emergent adverse events (TEAEs), total AEs, and serious adverse events (SAEs)	24 months

Collaborators and Investigators

• Sponsor: CUTISS AG
• Collaborators: RCTs

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: December 9, 2024
• First Submitted That Met QC Criteria: December 17, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 24, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Scars; Epidermis; Wound healing; Skin; Burns; Dermis; Thermal burns
• Additional Relevant MeSH Terms: Wounds and Injuries; Burns
• Other Study ID Numbers: dS-BA-PIII

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No