The status of clinical trials in automated tissue therapy for burn victims

An image to illustrate automated tissue therapy for burn victims
© WyssZurich-1

CUTISS’ CEO, Dr Daniela Marino, explains the company’s current challenge of clinical trials of automated tissue therapy for burn victims.

The context for automated tissue therapy for burn victims

Skin is the largest organ of the human body and is composed mainly of an outer epidermis and an inner dermis. It is our interface to the outer world and its total loss is incompatible with life. In contrast to a small skin lesion, if large proportions of epidermis and dermis are lost, the resulting full-thickness defects (FTSD) represent a significant, and sometimes unsolvable, problem for surgeons. The classical conditions that often lead to extended full thickness skin loss are burns, avulsion injuries, septic skin necroses, and iatrogenic skin defects.1

Today, FTSD is treated by means of skin autografting: a split-thickness skin graft (STSG) is harvested from a healthy donor site of the patient’s body and transplanted on to the full-thickness of the wound. STSG, being composed of epidermis but only remnants of dermis, are thinner than the wounds, thus, after transplantation, scar tissue is deposited to fill up ‘the gap’ and contraction is promoted to try and reduce the volume of the wound.

Moreover, during the acute phase, donor site shortage represents an unmet need that can potentially be lethal. In the mid-long term, scarring becomes the major issue as scars are indeed not just disfiguring but also debilitating and highly discomforting. They can also be painful and can impair mobility and growth, and require corrective surgeries, intense homecare, and psychosocial rehabilitation.1

The Solution

DenovoSkin™ is a personalised bio-engineering dermo-epidermal skin graft, that offers a solution to the lack of permanent skin coverage. It is an Advanced Therapy Medicinal Product (ATMP) developed at CUTISS, which is made up of cells that are isolated from a stamp-sized patient’s split-thickness biopsy. It also comprises both an epidermal and a dermal component. As such, there is no issue of rejection after transplantation, resulting in the product being safe for use.

Currently, denovoSkin™ is manufactured with a classical manual procedure. However, CUTISS’ research and development team is working full speed on the scale-up and automation of the manufacturing process, supported by a H2020 SME Instrument grant (see: http://cutiss.swiss/h2020-sme/). The main goal is to position denovoSkin™ as the first-in-class automatically-produced tissue therapy that can treat patients in a safe, effective, and accessible way.

The clinical trial status: recruiting

DenovoSkin™ has received Orphan Drug Designation for the treatment of Burns by Swissmedic, EMA and FDA. After a successfully-completed safety Phase I, the clinical trial2 is now in Phase II of efficacy trials in Europe (NCT03227146, NCT03229564, NCT03394612). DenovoSkin™ is a safe product and now the success of the efficacy trials is directly dependent on patients’ willingness to participate in the study.
More countries may be added soon, but we are currently actively recruiting in Switzerland (University Children’s Hospital (see: https://www.kispi.uzh.ch/de/Seiten/default.aspx)), University Hospital in Zurich, (see: http://www.en.usz.ch/Pages/default.aspx), in the Netherlands (VUmc Center in Amsterdam (see: https://www.vumc.com/)) and Dutch Burn Centre in Beverwijk (see: https://www.rkz.nl/dutchburn
centrebeverwijk).

We can recruit pediatric and adult patients with acute burns, but also those with a need for elective skin grafting (such as scar reconstruction, tumours, nevi, plastic surgery, etc.). In the centers mentioned, our excellent team of surgeons will be able to help patients that are in need of skin grafts, using the best standard of care. Furthermore, by participating in these trials and receiving denovoSkin™, patients will have the chance to actively and significantly contribute to the developing programme of a potentially breakthrough technology that will be able to heal millions on patients in need worldwide.

The skin transplantation field, especially in burns, has waited long enough for an innovative and effective therapy. It takes great teamwork and commitment from CUTISS, surgeons, patients, patient associations, scientists, and investors to now make it happen. For more information see CUTISS.

Burns and reconstructive clinical trials: adult and paediatric patients needed

Three Phase IIb, intra-patient randomised controlled burn clinical trials are currently being conducted on a variety of participants, involving adult patients aged 18 and over, and paediatric patients.

All three studies evaluate the safety and efficacy of an autologous bio-engineered dermoepidermal skin substitute (EHSG-KF), for the treatment of partial deep dermal and full thickness burns in adults, in comparison to autologous split-thickness skin grafts (STSG).

Burn clinical trial: adult patients

Conducted on patients aged 18 and over who need a skin graft due to a skin burn, this study in particular examines and compares the safety and efficacy of a transplant product (denovoSkinTM) made from the patient’s own skin with the current standard method, i.e. the transplantation of a thin autologous skin graft (split-thickness skin graft).

Two burned skin areas are selected and based on a random distribution, one skin area will be treated with denovoSkinTM and the other with the patient’s own skin. During the visits after the transplantation, both grafts will be checked for their safety and efficacy. The entire study lasts about 12 months per patient and includes ten study visits. In addition, yearly follow-up visits take place after two and three years after transplantation.

Burn clinical trial: paediatric patients

This study examines and compares the safety and efficacy of a transplant product (denovoSkinTM) made from the patient’s own skin with the current standard method, i.e. the transplantation of a thin autologous skin graft (split-thickness skin graft), in patients who need a skin graft due to a skin burn.

This study is being conducted on patients, aged one to 17 years old who require a skin graft due to a skin burn. Two burned skin areas are selected and based on a random distribution, one skin area will be treated with denovoSkinTM and the other with the patient’s own skin. During the visits after the transplantation, both grafts will be checked for their safety and efficacy. The entire study lasts about 12 months per patient and includes ten study visits. In addition, yearly follow-up visits take place after two and three years after transplantation.

The reconstructive clinical trial on paediatric and adult patients

This study is being conducted in persons from one year of age who require a skin graft due to a reconstructive surgery and examines and compares the safety and efficacy of a transplant product (denovoSkinTM) made from the patient’s own skin with the current standard method, i.e. the transplantation of a thin autologous skin graft (split-thickness skin graft).This can be due to a removal of a scar, a congenital nevus, a benign skin tumour, or due to gender reassignment surgery.

Two areas are selected and based on a random distribution, one skin area will be treated with denovoSkinTM and the other with the patient’s own skin. During the visits after the transplantation, both grafts will be checked for their safety and efficacy. The entire study lasts about 12 months per patient and includes ten study visits. In addition, yearly follow-up visits take place after two and three years after transplantation.

A company with a solid backbone

CUTISS is a spin-off of the University of Zurich (UZH) and was incorporated in March 2017. Until then, denovoSkin™ was being developed at the Tissue Biology Research Unit (TBRU), a laboratory associated with the Department of Surgery of the University Children’s Hospital in Zurich, Switzerland, where close collaboration between researchers and surgeons was envisioned to be the ideal substrate to succeed.

The message from the clinical team was clear: donor site shortage and scarring have often no solution. The mission for the scientists was clear: creating a real, innovative and, effective alternative to autografting. After completion of the Safety Phase I trials funded by the FP7 EU programme, in October 2016 the startup incubator Wyss Zurich (see: http://www.wysszurich.uzh.ch/projects/wyss-zurich-projects/denovoskin/) decided to financially support the Phase II trials for denovoSkin™.

In July 2017, soon after incorporation, the newly-funded UZH Life Science Fund, a joint venture of UZH Foundation and Novartis Venture Fund, injected a seed round of 1m CHF (~€0.88m) to launch the automation of production of denovoSkin™. In May 2018, CUTISS Ltd closed a Series A funding with 7.255m CHF (lead investor, Giammaria Giuliani, from Giuliani Pharma) and received the H2020 SME Instrument grant for €2.5m. This financing will now take the company to the next level, all the way forward to 2020. CUTISS’ team is now composed of 18 people involved in R&D, automation, production, and clinical trials.

This is a very strong, experienced team that works in close relation with clinical, regulatory, and engineering partners. CUTISS Ltd was awarded with prestigious prizes in Switzerland: the best pitch at the Swiss startup day in 2014, the TOP1 Swiss business plan 2015, the De Vigier prize in 2017, and is in 2018 TOP5 Swiss startup-TOP1 Swiss biotech.

References

1 Marino D., Reichmann E. , Meuli M. ‘Skingineering’. Eur J Pediatr Surg. 2014 Jun;24(3):205-13. doi: 10.1055/s-0034-1376315. Epub 2014 Jun 11
2 Meuli M. et al. ‘A Cultured Autologous Dermo-Epidermal Skin Substitute for Full Thickness Skin Defects: A Phase I, Open, Prospective Clinical Trial in Children. Plastic and Reconstructive Surgery’. Printing in process. To be published in June 2019

Dr Daniela Marino
CEO
CUTISS AG
+41 76 230 80 46
daniela.marino@cutiss.swiss

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