Investigational treatments and dose regimen
STERILE
MRG-001 is a combination product of Plerixafor (AMD3100) and Tacrolimus (FK506) with excipients for subcutaneous injection. Each 1 mL vial of MRG-001 contains 24 mg/mL Plerixafor and 0.5 mg/mL Tacrolimus. Sterile 0.9% sodium chloride solution for subcutaneous injection served as placebo.The dose selection was based on established clinical experience with each active pharmaceutical ingredient (API), effective dosages in animal models as well as its safety profile in nonclinical toxicological studies in two species. Subjects were enrolled in 3 sequential cohorts (cohort 1: 0.005 mL/kg, cohort 2: 0.01 mL/kg, cohort 3: 0.02 mL/kg MRG-001 or 0.9% saline placebo) of 6 subjects each, of which 4 subjects were randomized to the MRG-001 group and 2 subjects to the placebo group. Subjects received subcutaneous injections in the abdominal area on days 1, 3 and 5 and were required to fast 1-h pre-dose and 1-h post-dose. Follow-up visits were conducted on days 6 and 7 and subjects were discharged and returned on day 12 for the end-of-study visit.Each cohort included a sentinel dosing group of 2 subjects (1 MRG-001 and 1 placebo) dosed at the same time, with dosing of the remaining cohort following review of 24 h safety results of both sentinel subjects. Dose escalation to the next cohort occurred after review of all available safety, tolerability and pharmacokinetic data by the data safety review committee consisting of the principal investigator, medical monitor, pharmacokinetics expert and the study sponsor’s physician.