AN OPEN-LABEL, CONTROLLED, RANDOMIZED, MULTICENTER, DOSE ESCALATION STUDY EVALUATING THE SAFETY AND EFFICACY OF STRATAGRAFT® SKIN TISSUE IN PROMOTING THE HEALING OF THE DEEP PARTIAL-THICKNESS COMPONENT OF COMPLEX SKIN DEFECTS AS AN ALTERNATIVE TO AUTOGRAFTING

Summary

Targeted enrollment for this study is up to 20 patients with complex skin defects due to thermal burns with surgical excision and autografting. Subjects will be sequentially enrolled in two cohorts of increasing treatment area receiving StrataGraft skin tissue. Two comparable wounds in each subject will be identified and randomized to receive StrataGraft tissue or an autologous skin graft. Two donor sites will be designated in a randomized fashion to provide a source of autograft skin for the control treatment site and, if needed, the StrataGraft treatment site. Both the StrataGraft skin tissue and autograft control will be placed on the treatment sites immediately after surgical excision of non-viable tissue. Safety assessments will include wound closure of the treatment sites at three months, monitoring of AE, vital signs, hematologic parameters, incidence of wound infection, and immunologic responses to StrataGraft tissue. In addition, persistence of allogeneic DNA in the StrataGraft tissue-treated sites will be evaluated at 3 months. Efficacy will be assessed by evaluating wound closure of the treatment sites, the percent area of the StrataGraft skin tissue treatment site requiring autografting by day 28, pain of the donor sites through day 28, and the appearance of the treatment sites, supported by clinical photography. Cosmesis of the treatment sites and donor sites will be evaluated at 3, 6, and 12 months.

The early stage, dose escalation study will be conducted in two cohorts of 5-10 subjects each. Cohort 1 will receive up to 220 cm2 of StrataGraft skin tissue and will have a comparable autografted control treatment area. Exposure of up to 220 cm2 StrataGraft tissue was shown in the previous phase I/IIa trial to be well tolerated for seven days with no evidence of safety concerns when applied to the full-thickness component, the most vulnerable area of complex skin defects. Patients in cohort 2 will receive up to 440 cm2 of StrataGraft tissue and will have a comparable autografted control treatment area. In contrast to the previous phase I/IIa study, StrataGraft tissue in both cohorts will be left in place rather than being removed after a defined period. Enrollment into the second cohort will begin only after the I-DSMB has reviewed the interim safety data and determined that there have been:

 No serious adverse events (SAE) deemed related to treatment with StrataGraft skin tissue
 No infection deemed related to treatment with StrataGraft skin tissue

Primary clinical endpoints
 Wound closure of the treatment sites at 3 months
 Percent area of the StrataGraft treatment site requiring autografting by day 28

Secondary clinical safety assessments
 AE
 Incidence of infection
 Vital signs
 Hematologic parameters
 Immunology assessments at baseline, day 28, and 3 months
 Archival plasma and leukocyte collection at baseline and 3 months
 Persistence of allogeneic DNA at 3 months

Secondary clinical efficacy assessments
 Cosmesis of donor sites at 3, 6, and 12 months
 Pain of donor sites measured by FACES pain rating scale at days 3, 7, 14, and 28
 Percent of patients requiring autografting of the StrataGraft treatment site by day 28
 Wound closure of the treatment sites at 7, 14, and 28 days, and 3, 6, and 12 months
 Percent wound closure at 7, 14 and 28 days, and 3, 6, and 12 months
 Cosmesis of treatment sites at 3, 6, and 12 months
 Appearance of treatment sites at days 3, 7, 14, and 28

Participant Eligibility

Patient-specific criteria:
1. Men and women aged 18-65 years, inclusive
2. Written informed consent
3. Sufficient healthy skin identified and designated as a donor site in the event that the StrataGraft treatment site requires autografting.

Wound-specific criteria:
4. Complex skin defects of 3-49% TBSA requiring excision and autografting
5. Total burn may consist of more than one wound area
6. Deep partial-thickness thermal burn(s) with total area of 88 to 880 cm2 requiring excision
and autografting
7. First excision and grafting of treatment sites