A Study to Evaluate the Efficacy and Safety of NexoBrid in Subjects With Thermal Burns
Condition: Thermal Burns
MeSH terms: Burns
Intervention: NexoBrid; Standard of Care (SOC); Gel Vehicle
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Single (Outcomes Assessor)
Enrollment: 175.0
Sex: All
Minimum age: 18 Years
Maximum age: 77 Years
Healthy volunteers: No
Keywords: fire/flame; scalds; contact

Summary:

      This study will be a three-arms study intending to demonstrate superiority of NexoBrid
      treatment over the Gel Vehicle placebo control treatment and over SOC in thermal burn
      subjects.

      The study objectives are:

        1. To demonstrate the efficacy of enzymatic eschar removal with NexoBrid by providing
           complete eschar removal as compared with Gel vehicle,

        2. To demonstrate the efficacy of enzymatic eschar removal with NexoBrid by providing
           earlier complete eschar removal, reduction in patients' surgical burden and its related
           blood loss as compared to SOC,

        3. To assess the safety of NexoBrid compared to SOC, including demonstration that treatment
           with NexoBrid does not cause an unacceptable level of harm on wound closure outcome and
           long term outcomes of cosmesis and function.
    

Eligibility criteria:

        Inclusion Criteria- Patient level

          1. Males and females; ≥ 18

          2. Thermal burns caused by fire/flame, scalds or contact,

          3. Patient total burns area ≥ 3% DPT and / or FT,

          4. Patient total burns area should be ≤ 30% TBSA; SPT, DPT and/or FT in depth,

          5. Informed consent can be obtained within 84 hours of the burn injury,

          6. Patients who are willing and able to sign a written consent form.

        Inclusion Criteria - Wound level

          1. At least one wound (a continuous burn area) that is ≥0.5% TBSA (DPT and/or FT) (this
             minimal wound size should not including face, perineal or genital area.

             All planned target wounds (TWs) should meet the following criteria:

          2. SPT area that cannot be demarcated from DPT and FT areas should be less than 50% of
             the % TBSA of the TW.

          3. Wound's blisters can be removed/ unroofed, as judged by the investigator.

        Exclusion Criteria- Patient level

          1. Patients who are unable to follow study procedures and follow up period.

          2. Modified Baux index ≥ 80,

          3. Patients with burned charred fingers, 3rd degree in depth and possibly devoid of
             circulation,

          4. Patients with abraded wound/s that cannot be treated by an enzymatic debrider
             application (NexoBrid) will be excluded from the study,

          5. Patients with electrical or chemical burns,

          6. Patients with circumferential (≥ 80% of the limb circumference) DPT and/or FT burns
             defined as Extremities at Risk (EAR) 2 as described in the protocol.

          7. The following pre-enrollment dressings: a. Flammacerium, b. Silver Nitrate (AgNO3),

          8. Patients with pre-enrolment wounds which are covered by eschar heavily saturated with
             iodine or by SSD pseudoeschar (e.g. pseudoeschar as a result of > 12 hours SSD
             treatment),

          9. Patients with pre-enrollment escharotomy.

         10. Patients with diagnosed infections as described in Section 11.9 of study protocol,

         11. Diagnosis of smoke inhalation injury.

         12. Pregnant women (positive pregnancy test) or nursing mothers.

         13. Poorly controlled diabetes mellitus (HbA1c>11%) in patients with known diabetes as
             captured in the medical history.

         14. BMI greater than 39.0 kg/m2 in patients with burn area up to 15% TBSA or BMI greater
             than 34.0 kg/m2 in patients with burn area more than 15% TBSA.

         15. ASA greater than 2 (Appendix 13- ASA classification system)

         16. Cardio-pulmonary disease (MI within 6 months prior to injury, 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).

         17. Pre-existing diseases which interfere with circulation (severe peripheral vascular
             disease, edema, lymphedema, regional lymph nodes, significant varicose veins),

         18. Any conditions that would preclude safe participation in the study or adding further
             risk to the basic acute burn trauma (such as 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)

         19. Chronic systemic steroid intake,

         20. History of allergy and/or known sensitivity to pineapples, papaya, Bromelain or
             papain,

         21. Current (within 12 months prior to screening) suicide attempt,

         22. Mentally incapacitated adults who are incapable of giving legal consent

         23. Enrollment in any investigational drug trial within 4 weeks prior to screening,

         24. Current (within 12 months prior to screening) alcohol or drug abuse (see definition in
             section 1.1)

         25. Prisoners and incarcerated,

         26. Patients who might depend on the clinical study site or investigator.