ACCS (Amnion-derived Cellular Cytokine Solution) Versus Standard Care In Treating Partial Thickness Burns

• The number of totally epithelialized (100%) wounds in the ACCS-treated wounds versus the number in the normal saline-treated wounds [ Time Frame: 21 days ] [ Designated as safety issue: No ]
• The percentage conversion to full-thickness wounds in the ACCS-treated wounds versus the conversion in the normal saline-treated wounds [ Time Frame: 21 days ] [ Designated as safety issue: No ]
• Quality of healing, including pruritis, and scar hypertrophy, and reduction in pain in the ACCS-treated wounds as compared to saline-treated wounds [ Time Frame: 21 days ] [ Designated as safety issue: No ]
• Quality of healing as assessed by hemoxylin and eosin staining of the punch biopsy taken on Day 21 in the ACCS-treated wounds as compared to saline-treated wounds [ Time Frame: 21 days ] [ Designated as safety issue: No ]
• Assessment of change in arterial circulation using a laser Doppler from baseline to Day 21 in the ACCS-treated wounds as compared to saline-treated wounds [ Time Frame: 21 days ] [ Designated as safety issue: No ]
• Determination of levels of 6 cytokines present in blood prior to treatment (baseline) and within one-hour of the first treatment for the initial 12 patients [ Time Frame: 21 days ] [ Designated as safety issue: No ]
• The primary safety endpoint will be the incidence of adverse events post-treatment. [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

The objective of this protocol is to perform a safety and dose-determination efficacy clinical trial in patients having a degree of partial-thickness burn wounds. The trial will be a prospectively randomized and double-blind trial of Amnion-derived Cellular Cytokine Solution (ACCS) compared with standardized care using 0.9% NaCl (normal saline) solution in the same three treatment regimens.

A Phase I/II multi-center clinical trial will be performed in 99 adults with partial-thickness burns. Two similar partial-thickness burn areas in a single patient will be selected. One burn will be randomly assigned to receive either test drug (ACCS) or normal saline in one of three treatment regimens.

The three treatment arms will be:

1. ACCS 0.01 mL/cm2 every 7th day vs. normal saline 0.01 mL/cm2 every 7th day;
2. ACCS 0.01 mL/cm2 every 4th day vs. normal saline 0.01 mL/cm2 every 4th day; and
3. ACCS 0.01 mL/cm2 every other day vs. normal saline 0.01 mL/cm2 every other day.

Two different preclinical studies of partial-thickness burns on guinea pigs have demonstrated accelerated epithelialization with topical treatment with ACCS. Similarly, preclinical studies in Yorkshire pigs have demonstrated more rapid maturity of epithelialization and better quality healing of partial-thickness skin graft donor sites with ACCS treatment.

In the preclinical studies, ACCS given in a dose of 0.01 mL/cm2 wound area appeared to saturate the wound adequately without excess and simultaneously improve healing. In preclinical toxicity studies, the dose of 0.01 mL/cm2 was shown to be safe.

• Experimental: 1
  Treatment every other day
  Intervention: Biological: ACCS (Amnion-derived Cytokine Suspension)
• Experimental: 2
  Treatment every 4th day
  Intervention: Biological: ACCS (Amnion-derived Cytokine Suspension)
• Experimental: 3
  Treatment every 7th day
  Intervention: Biological: ACCS (Amnion-derived Cytokine Suspension)

Inclusion Criteria:

• A signed IRB- approved Informed Consent Form;
• 18 - 65 years of age;
• Two (2) similar, non-contiguous, partial-thickness burn wounds between 50 cm2 and 250 cm2 in area with blisters removed in a Total Body Surface Area(TBSA) burn of less than or equal to 40% TBSA;
• Burns must be thermal burns of flame or scald etiology;
• Patient must present to the burn center within 8 hours of injury;
• Normal creatinine and bilirubin levels;
• If capable of bearing children, patient must be using a medically accepted means of birth control and have a negative serum pregnancy test;
• Willing to participate in the clinical study and comply with the requirements of the trial.

Exclusion Criteria:

• The two (2) chosen wounds must not be full-thickness (extending through the dermis into the subcutaneous tissue);
• Thermal burn from chemical, electrical or radiation causes;
• Neither the study wound nor the comparator wound can be < 50 cm2 or >250 cm2 in size and cannot be on the face or hands;
• Patients with significant pulmonary injury, i.e., smoke inhalation injury requiring ventilator support;
• Patients with diabetes;
• Patients with any immune deficiency including current treatment with corticosteroid medication, chemotherapeutic agents, anti-viral therapy, or concurrent radiation therapy within 30 days of signing the informed consent;
• Abnormal bilirubin, liver function studies (i.e., AST, ALT> 2.0 times normal);
• Abnormal serum creatinine, receiving hemodialysis or peritoneal dialysis;
• Active cancer or a history of cancer in the 5 years prior to signing the informed consent form (history of basal cell carcinoma is allowed);
• Psychiatric condition or substance abuse which in the Investigator's opinion may pose a threat to patient compliance;
• History of non-compliance with treatment or clinical visit attendance.
• Patients whose burns were previously treated with anything other than ice, cold water or dry dressing.
• Participation in an investigational trial within 30 days of study entry.