Clinical trial procedure
infection, agitation, erythema, blood coagulation
ERYTHEMA, INDURATION, STERILE, INFECTION, ADVERSE REACTION
All participants provided informed, written consent to participate in the trial after discussion with the Principal Investigator or Sub‐Investigator. Clinical pEVs, which consisted of a sterile formulation of the LEAP‐purified human non‐autologous pEV (300 μg/mL) in an isotonic solution containing sodium chloride, histidine, sucrose, polysorbate 20, and water for injection, was stored at −80°C (± 15°C). The placebo, which consisted of the same isotonic solution, minus the pEVs, was also stored at −80°C (± 15°C). On the day of dosing, the selected vials of clinical pEVs and placebo were transferred to a 2–8°C refrigerator to thaw for 1 h before administration. After removal from the storage refrigerator for administration, each vial was gently hand warmed to ambient temperature with gentle agitation to prevent foaming.On Day 0, participants underwent physical examination, including vital signs recording (blood pressure, pulse rate, respiration rate, and temporal temperature). They received a bilateral 4 mm skin biopsy to each inner upper arm using a sterile punch following a standard clinical practice. Participants were administered a single dose (100 μg in 340 μL) of clinical pEVs injected subcutaneously adjacent to the assigned arm wound site and an equivalent volume (340 μL) of placebo injected subcutaneously to the comparator wound site. Participants and trial investigators were blinded as to which treatment had been administered to which arm. Wounds were dressed using standard of care procedures. Participants were observed in the outpatient clinic for 1 h following treatment, noting any local adverse reaction at the injection site. Participants were then discharged.The safety of the clinical pEVs was monitored over the next 30 days. On Day 3, the site healthcare professional removed the dressing from the participant, and the wound was washed with sterile saline before the examination. The blinded follow‐up assessor(s) did not have access to participant study notes recording to which arm clinical pEVs/placebo was administered. A physical examination and vital signs check were conducted on days 3, 7, 14, and 30. The wound sites were examined for erythema, induration, exudate, fibrin coverage, wound margin, granulation issue, evidence of infection, and wound closure rate.To further assess the safety of the intervention, the general laboratory blood examination performed during participant screening was repeated on days 7, 14, and 30 by taking blood samples for complete blood examination (red blood cells, white blood cells, haemoglobin, hematocrit, erythrocyte sedimentation rate, platelets), blood coagulation factors (activated partial thromboplastin time, prothrombin time and thrombin time) and general biochemistry for metabolites and hormones (liver function tests, C‐reactive protein, creatinine, urea, albumin, haemoglobin A1c, blood glucose, glomerular filtration rate, cholesterol and thyroid stimulating hormone).