Mallinckrodt plc's pivotal Phase 3 clinical trial evaluating the efficacy and safety of a single application of StrataGraft regenerative tissue in the treatment of deep partial-thickness thermal burns met both primary endpoints.
The pivotal open-label, controlled, randomized, multicenter Phase 3 trial in adults evaluated the efficacy and safety of a single application of StrataGraft tissuein the treatment of deep partial-thickness thermal burns. The study enrolled 71 study participants across 12 clinical sites in the United States. Study participants were age 18 years and older and had three to 49% total body surface area complex skin defects caused by thermal burns that contained intact dermal elements for which surgical excision and autografts were clinically indicated. The study design used an intra-patient control, in which two similar areas of burn injury on the same study participant were randomly assigned to either standard of care (autograft) or StrataGraft treatment.
The co-primary endpoints included autograft sparing (the difference in the percent area of thermal burn wounds treated with StrataGraft tissue that required autografting compared with the control autograft treatment sites by three months), and durable wound closure (the proportion of study participants achieving durable wound closure of the StrataGraft-treated site at three months without autograft placement).
Key co-primary endpoints findings included the following:
- On average, 4% of the area of StrataGraft-treated sites required autografting by three months. By design, 100% of the area of control-treated sites was autografted and an additional 2% of the area required subsequent autografting by three months. This resulted in a 98% reduction in the area requiring autograft in the StrataGraft-treated sites compared to the control-treated sites (p<0.0001).
- 83% of burn wounds treated with StrataGraft tissue alone achieved durable wound closure at the treatment site at three months post-placement (95% confidence interval: 74.4-91.8%, meeting the pre-defined threshold of statistical significance). As a reference, 86% of the burn wounds treated with a single application of autograft achieved durable wound closure at three months post-placement (95% confidence interval: 77.8-94.0%).
The safety profile of StrataGraft tissue was comparable to that of autograft. Pruritus was the most commonly reported treatment-emergent adverse event (TEAE), occurring in 25 of 71 (35%) study participants treated with StrataGraft tissue (of which 11 of the 25 were possibly related to study treatment). All study treatment-related TEAEs were mild or moderate in severity. No local infections were related to StrataGraft treatment.
Based on the positive Phase 3 data, Mallinckrodt plans to submit a Biologics License Application for StrataGraft tissue to the FDA in the first half of 2020. StrataGraft tissue is an investigational product, and its safety and effectiveness have not yet been established by the FDA.
“Treatment advances are needed that can help minimize or eliminate the need to harvest skin tissue for autografting, as the second wound created by removing healthy skin can be associated with complications and can be even more painful than the burn wound itself,” said Dr. James H. Holmes IV, study co-lead investigator and Director of Wake Forest Baptist Medical Center's Burn Center. “The positive top-line results of the Phase 3 trial suggest that this investigational regenerative tissue, if approved, could provide burn surgeons with an alternative treatment option for deep partial-thickness burns.”
Autograft is considered to be a standard of care by many for deep partial-thickness thermal burns. Such burns are complex skin injuries in which the damage extends through the entire epidermis (outermost layer of skin) and into the lower part of the dermis (innermost layer of skin). As autograft involves the surgical harvesting of healthy skin from an uninjured site on the patient and transplanting the skin graft to the injury, patients are left with two wounds requiring care. Patients who receive an autograft may experience pain, itching, scarring and impaired function at the donor site.
“Achieving the co-primary endpoints in our pivotal Phase 3 trial and exceeding statistical thresholds for both endpoints represents an important development milestone for StrataGraft tissue, which has the potential to help patients suffering from deep partial-thickness thermal burns. Coupled with the recently announced positive Phase 3 results for terlipressin in hepatorenal syndrome,or HRS, type 1, these Phase 3 results demonstrate our ability to design and execute successful development programs targeting complicated, serious conditions,” said Steven Romano, MD, Executive Vice President and Chief Scientific Officer at Mallinckrodt.“We are committed to providing StrataGraft to patients in need as a potential paradigm-changing treatment and alternative to autograft, if approved. We would like to thank the study participants and investigators in the Phase 3 clinical trial and all of the others who have helped us advance the clinical development program for this investigational product.”