Clinical trial NCT04040660: Use of NexoBrid for Treatment of Acute Deep Partial and Full Thickness Burn Injuries
Official title: Use of NexoBrid for Treatment of Acute Deep Partial and Full Thickness Burn Injuries
Study type: EXPANDED_ACCESS
Overall status: APPROVED_FOR_MARKETING
Conditions: Thermal Burn
Lead sponsor: MediWound Ltd
Sponsor class: INDUSTRY
First posted: 2019-08-01
Sex: ALL
Minimum age (years): 0
Standard ages: CHILD
ADULT
OLDER_ADULT

Brief summary: Enzymatic eschar removal with NexoBrid allows initiating and completing the phase of removal of the offending eschar earlier upon admission, enabling earlier visualization of the wound bed for assessment of burn wound depth as well as preservation of viable dermal tissues, as further elaborated and supported by previous clinical studies. The depth determination is important for the planning and execution of the post eschar removal stage of wound closure phase (grafting or spontaneous epithelialization).

Additional clinically meaningful attributes of NexoBrid enzymatic eschar removal is the ability to lower surgical burden as it allows to remove eschar in wounds that otherwise would have to undergo surgical excision as no other non-surgical treatment is available for early and effective eschar removal.

MediWound has completed the recruitment of patients to study MW2010-03-02 (DETECT Study). The timeline for patients' follow-up and potential for approval in 2021/2022, creates a significant gap in the ability of clinical practitioner's to maintain their knowledge and skills in using NexoBrid as they no longer treat eligible patients. The expanded access protocol will allow to expand treatment to additional patients in up to 30 US burn centers (DETECT sites and additional sites). The proposed protocol will allow product availability to eligible population and keep the clinical use of the product knowledge active in the burn care community introducing it to their routine burn care.

The BLA assessment was completed and NexoBrid is approved for use in adults in the US. Adult enrollment is closed, and only pediatric patients will continue to be recruited for this treatment protocol.

The purpose of this treatment protocol is to provide NexoBrid to patients with DPT and FT thermal burns on up to 30% TBSA.

This protocol is also designed to collect and evaluate the safety and clinical performance of NexoBrid in this patient population.

Detailed description: This is an Expanded Access (treatment) protocol to allow ongoing treatment of burn patients with NexoBrid following completion of the enrollment stage of protocol MW2010-03-02 (DETECT study).

This protocol is also designed to collect and evaluate the safety and clinical performance of NexoBrid in patients suffering from DPT and FT thermal burns.

Following the enrollment of a patient to the protocol, physicians will identify one or more target wounds (TWs) per patient according to the TW definition. All patient's DPT and FT burns that comply with the specified entrance criteria will be treated with NexoBrid and, therefore, must be designated as TWs. This will further allow an evaluation of the patient's systemic safety by allowing treatment of the patient's entire deep burns.

Prior to initiation of eschar removal treatment, patients will be medicated with appropriate analgesia and undergo wound cleansing and dressing of all wounds with antibacterial solutions according to product instruction for use in order to ensure clean and moist eschar covered wound bed for NexoBrid application. Vital signs (Blood Pressure, Heart Rate and temperature) measurements and pain assessment will be performed within 24 hrs before start of treatment as well as haematology, biochemistry blood tests \& PTT/INR. Pressure measurements for circumferential extremity wounds will be performed 1 hour before start of treatment and will be closely monitored during treatment. Following wound cleansing and soaking treatments, patients will undergo the eschar removal process. TWs of up to 15% total body surface area (TBSA) will be treated with a single application of NexoBrid for 4 hours. Patients with TWs \>15% TBSA and up to 30% TBSA will be treated with 2 consecutive applications of 4 hours each. NexoBrid should not be applied to more than 15% TBSA in one session. PK samples will be taken from sub-set of patients with TWs area \>15% TBSA. Pressure measurements for circumferential extremity wounds will be performed after the removal of NexoBrid.

Post eschar removal completion, patients will undergo daily vital signs (Blood Pressure, Heart Rate and temperature measurements) and pain assessments for 1 week, starting on the morning following start of eschar removal. Blood tests (haematology and biochemistry) will be performed 24 ± 6 hrs post eschar removal as well as PTT/INR. Weekly assessments of wound healing progress including the dressings used until complete wound closure will be performed.

Cosmesis (scar quality) evaluation (using MVSS) will be performed at 3 and 12 months post wound closure confirmation visit.

Eligibility criteria: Inclusion Criteria patient level:

1. Pediatric only (0 to \< 18years old) males and females
2. Thermal burns caused by fire/flame, scalds or contact,
3. Patient total burns area ≥ 1% DPT and / or FT with eschar that should be removed in SOC,
4. Patient total burns area to be treated should be ≤ 30% TBSA; SPT, DPT and/or FT in depth,
5. Informed consent can be obtained within 84h of the burn injury,
6. Patients and/or legal authorized representative who are willing and able to sign a written consent .

Inclusion Criteria - Wound level

* At least one wound (a continuous burn area) that is ≥0.5% TBSA (DPT and/or FT) (this minimal wound size should not include face, perineal or genital)

All planned TWs should meet the following criteria:

* SPT areas that cannot be demarcated from DPT and FT areas should be less than 50% of the % TBSA of the TW,
* Wound's blisters can be removed/ unroofed, as judged by the investigator.

Exclusion Criteria patient level:

1. Patients weighing less than 3kg,
2. Patients with burned, charred fingers, 3rd degree in depth and possibly devoid of circulation,
3. Patients with abraded wound/s that cannot be treated by an enzymatic debrider application (NexoBrid),
4. Patients with pre enrolment escharotomy,
5. Patients with electrical or chemical burns,
6. The following pre-enrollment dressings: a. Flammacerium, b. Silver Nitrate (AgNO3),
7. Patients with pre-enrolment wounds which are covered by eschar heavily saturated with Silver, Iodine or by SSD pseudoeschar (pseudoeschar as a result of \> 12 hrs SSD treatment),
8. Patients with diagnosed infections as described in the protocol,
9. Diagnosis of smoke inhalation injury \[12\],
10. Pregnant women (serum positive pregnancy test) or nursing mothers,
11. Poorly controlled diabetes mellitus (HbA1c\>11%) in patients with known diabetes as captured in the medical history,
12. BMI greater than 40.0 kg/m2,
13. American Society of Anesthesiologists (ASA) physical status classification system greater than 2
14. Cardio-pulmonary disease (MI within 6 months prior to injury, severe or unstable Ischemic Heart Disease, severe or unstable heart failure, severe pulmonary hypertension, severe COPD or pre-existing oxygen-dependent pulmonary diseases, severe broncho-pneumonia within 1 month prior to injury, steroid dependent asthma or uncontrolled asthma),
15. Pre-existing diseases which interfere with circulation (severe peripheral vascular disease, severe circulatory edema and/or lymphedema, regional lymph nodes dissection, significant varicose veins),
16. Any conditions that would preclude safe treatment or adding further risk to the basic acute burn trauma (such as a positive COVID test, severe immuno-compromising diseases, life threatening trauma, severe pre-existing coagulation disorder, severe cardiovascular disorder, significant pulmonary disorder, significant liver disorder including post alcoholic abuse impaired function or neoplastic disease, blast injury),
17. Chronic systemic steroid intake,
18. History of allergy and/or known sensitivity to pineapples, papaya, Bromelain or papain.
19. Enrollment in any investigational drug trial within 4 weeks prior to screening.

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Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Mobile
country: United States
facility: University of South Alabama
state: Alabama
city: Phoenix
country: United States
facility: Valleywise Health Medical Center
state: Arizona
city: Orange
country: United States
facility: University of California, Irvine
state: California
city: Bridgeport
country: United States
facility: Bridgeport Hospital
state: Connecticut
city: Washington
country: United States
facility: Medstar Washington Hospital Center
state: District of Columbia
city: Gainesville
country: United States
facility: Shands Children's Hospital, University of Florida
state: Florida
city: Gainesville
country: United States
facility: University of Florida, Department of Surgery
state: Florida
city: Miami
country: United States
facility: Jackson Memorial Hospital
state: Florida
city: Atlanta
country: United States
facility: Grady Memorial Hospital
state: Georgia
city: Indianapolis
country: United States
facility: Eskenazi Hospital
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Kansas City
country: United States
facility: The University of Kansas Hospital
state: Kansas
city: New Orleans
country: United States
facility: University Medical Center New Orleans
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins Bayview Medical Center, Burn Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: Hennepin Healthcare
state: Minnesota
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Akron
country: United States
facility: Akron Children's Hospital
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Portland
country: United States
facility: Legacy Oregon Burn Center
state: Oregon
city: Allentown
country: United States
facility: Lehigh Valley Hospital and Health Network
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Mercy Burn Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: West Penn Hospital
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: Parkland Health & Hospital System, Burn Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Hospital
state: Utah
city: Seattle
country: United States
facility: Harborview Medical Center
state: Washington
city: Milwaukee
country: United States
facility: Colombia St Mary's Hospital
state: Wisconsin
Study officials:
References: