Burn Injury
Conditions
Keywords
Maximum tolerated dose, Debridement
Brief summary
This study will examine the tolerability of a gel formulation of the enzyme SN514 in patients with burns suitable for enzymatic debridement. In a rising dose fashion by sequential cohort, concentrations of 0.1%, 0.2%, 0.4% and 0.8% will be tested. Groups of 3 will undergo daily debridement for up to 7 days. Extent of debridement and adverse signs and symptoms will be recorded daily. Dose escalation will stop if a dose level is found to be intolerable. Dose escalation may accelerate if a tested dose is entirely ineffective. There is no placebo control as all burn wounds require debridement.
Detailed description
The design of the study is a sequential rising dose to the maximum tolerated dose, in which each subject will be exposed to only one concentration of the test article. Dose limiting toxicities are defined as "Severe" or CTCAE v5 Grade 3 or higher adverse events. This study in burn patients is designed to apply SN514-066b over 25 cm2 (0.14% TBSA for a 1.73 m2 adult) up to 500 cm2 (2.9%), at sequentially rising concentrations of 0.1%, 0.2%, 0.4% and 0.8% (< 1.0 mg/cm2). The highest exposure would be 0.8% (8 g per 100 cc of gel) over 2.9% of 1.73 m2 = 800 mg or 11.4 mg/kg applied topically (70 kg patient).
Interventions
BIOLOGICALSN514-066b
Enzyme debrider
Sponsors
SERDA bv
The Metis Foundation
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: 1. Thermal burns caused by fire/flame, scalds or contact 2. Total burns area available for treatment is 25 to 500 cm2 (a larger area may be burned, but the treatment area must be limited to the stated size, and the treatment area must be exclusive of face, hands, genitalia and sites deemed to be at high risk for developing compartment syndrome) 3. Target burns for treatment is deep partial thickness (DPT) in depth Main
Exclusion criteria
1. Subject has another life threatening traumatic injury 2. Patient's proposed study wound site has any of the following conditions: * Electrical or chemical etiology * Pre-enrollment escharotomy * Area is devoid of circulation * Located on the face, perineum or genitalia * Clinical evidence of wound infection 3. Poorly controlled diabetes mellitus (HbA1c \>12%) 4. BMI greater than 40 kg/m2 5. 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) 6. Pre-existing diseases which interfere with circulation (severe peripheral vascular disease, severe circulatory edema and/or lymphedema, regional lymph nodes dissection, significant varicose veins) 7. Any conditions that would preclude safe treatment 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determine the maximum tolerated concentration of SN514 gel when applied topically to deep partial thickness burn wounds | Daily x 7days | Number of participants with treatment-related adverse events of Grade 3 or higher as assessed using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0, where a higher grade on the scale of 1 to 5 is a worse outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate effects of treatment on inflammation | Daily x 7days | Changes from baseline to end of treatment in blood levels of C-reactive protein (CRP) in mg/dL, serum tryptase in ng/mL, and total complement activity (CH50) level in hemolytic units. |
| Observe the incidence of wound erythema | Daily x 7days | Record daily the appearance of new, spreading or darkening redness of the treated or adjacent tissue |
| Incidence of wound purulence | Daily for 7 days | Observe daily for the appearance of purulent material in the treatment area |
| Evaluate the time course and extent of debridement when applied daily for up to 7 days | Daily x 7days | Percent of eschar removed following each 24 hr debridement |
Countries
United States
Outcome results
None listed