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.

This is a multi-center, multi-national, randomized, controlled, assessor blinded, three-arm study aiming to demonstrate superiority of NexoBrid treatment over Gel Vehicle control and over SOC treatment in thermal burn subjects with burns. Following the enrollment of a patient to the study and prior to randomization Physicians will define one or more Target Wounds (TWs) per subject according to TWs definition. All subjects' deep (DPT and FT) burns that comply with the specified entrance criteria are intended to receive study treatment per the randomized study arm.

The randomization procedure will be initiated only after all Target wounds of a subject have been defined. Patients will be assigned to the treatment arm in a 3:3:1 ratio (NexoBrid: SOC : Gel Vehicle).

Patients will be treated in the same way in all study arms (NexoBrid, SOC or Gel vehicle) except for the eschar removal stage which will be performed as per the randomization study arm.

Prior to initiation of eschar removal treatment, subjects will be medicated with appropriate analgesia and undergo wound cleansing and dressing of all wounds with antibacterial solutions . Following wound cleansing and antibacterial treatments, subjects will undergo the eschar removal process as per treatment assignment (NexoBrid, SOC or Gel Vehicle, following randomization).

Subsequent to complete eschar removal, all wounds will be assessed and treated in the same manner, in accordance with post-eschar removal wound care strategy. Post eschar removal, subjects will undergo daily vital signs and pain assessments, until hospital discharge (HD) and weekly assessments of wound progress, until wound closure. Following wound closure confirmation visit, subjects will be followed up at 1, 3, 6, 12, 18 and 24 months post wound closure for long term outcomes evaluation.

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.