A Phase 1/2 Trial of PTR-01 in Adult Patients With Recessive Dystrophic Epidermolysis Bullosa (RDEB)

Protocol PTR-01-001 is a saline-controlled, single and repeat dose, dose-escalation, crossover study designed to determine the safety, tolerability, tissue kinetics, pharmacodynamics and preliminary efficacy of PTR 01. The study is divided into three periods: an up to 4-week Screening Period, a 10-week Treatment Period and an 8-week Follow-up Period. During the Screening Period and Follow-up Period there will be no study drug treatment. During the Treatment Period a total of 3 doses of PTR-01 and 3 doses of saline control will be administered to patients for a total of 6 doses over a 10-week period in three cohorts dosed at 0.1, 0.3, 1.0 and 3.0 mg/kg (active drug). Twelve patients with a diagnosis of RDEB and a history of at least one chronic wound will be enrolled. Those patients who do not have documentation of genetic analysis and IF staining will have blood for genetic analysis and a biopsy for IF staining prior to enrollment (both required). Cohorts 1, 2, 3 and 4 will consist of 2, 4, 3 and 3 patients respectively. Each cohort will consist of patients divided into two groups (Group 1 and Group 2) randomized in a 1:1 ratio. Patients will receive doses 2 weeks apart. Patients in Group 1 will receive three doses of active drug followed by 3 doses of saline control. Patients in Group 2 will receive three doses of saline control followed by 3 doses of active drug. This cross-over design will yield a total of 14 patients all of whom will receive active drug and saline control. Prior to randomization, patients will complete a Screening Period to assess the extent and impact of skin disease involvement and the chronicity of at least one wound. Only patients who meet all of the eligibility criteria will be randomized for treatment. Cohort 1 patients randomized to Group 1 will receive 3 doses of active treatment (PTR-01) at a dose of 0.1 mg/kg followed by 3 doses of saline control for a total of 6 doses. Cohort 1 patients randomized to Group 2 will receive 3 doses of saline control followed by 3 doses of active treatment (PTR-01) at a dose of 0.1 mg/kg for a total of 6 doses. After the last patient in Cohort 1 has received their third dose and safety labs for all patients have been reviewed by the Data Safety Monitoring Board (DSMB), the next cohort may be enrolled. This same schedule and safety review process will be followed for all subsequent dosing cohorts, with Cohort 2, Cohort 3 and Cohort 4 receiving 0.3, 1.0 and 3.0 mg/kg respectively. Efficacy assessments will be performed prior to first dose of therapy (at the end of the Screening Period), after the last dose of study drug in Period 1, after the last dose of study drug in Period 2 of the Treatment Period and 2 weeks (Day 85) after the last dose of study drug (at the end of the Follow-up Period).