This is a randomized, single-blind, single-center, concurrently controlled, exploratory, Phase I study to determine the in vivo kinetics (24-hour post-infusion recovery and T50 survival) of EryDex System (EDS) -processed autologous red blood cells (RBC) in non-patient volunteers. A total of 12 non-patient volunteer subjects will be enrolled and assigned to one of the 2 groups (6 subjects in active arm group, 6 subjects in sham arm group).
EryDex System (EDS) is a combination product used to administer dexamethasone sodium phosphate (DSP) by ex vivo encapsulation in autologous erythrocytes which are re-infused. DSP is dephosphorylated in RBCs to release dexamethasone. The 12 subjects who meet all of the inclusion/exclusion criteria will be assigned to one of the 2 groups, consisting of 6 subjects each, as follows: * Group 1 (active drug arm): 15-20 mg DSP loaded in RBC using the EDS. * Group 2 (sham arm): sham treated autologous RBC using the EDS One 50±5mL aliquot of blood collected from each subject will be treated using the EDS process (either active drug or sham) and the resultant processed RBCs will be radiolabeled with Chromium-51 (51Cr) for the in vivo kinetic study. A second 10±5mL simultaneously collected sample will be labeled with Technetium-99m (99mTc) to estimate the subject's blood volume. These labeled aliquots will be mixed, and simultaneously infused through a peripheral vein via butterfly or similar catheter (total dose 20-40 μCi). Blood samples will be collected from the subject's contralateral arm immediately pre-infusion and at 5, 7.5, 10, 12.5, 15, 20, and 30 minutes (± 3 min), and on Day 1, 24 hours (±2 h) after completion of infusion. Vital signs will be assessed after the 30-min sample on Day 0 and again on Day 1 before the 24-h sample is collected. Additional blood samples will be collected at 48 (±4 h) and 72 (±4 h) hours and 7 (±1 d) days post-infusion, and then weekly through 49 days post-infusion, with a window of ±2 days for each visit.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
10
Intravenous infusion of 10 mg DSP encapsulated in autologous erythrocytes. Peripheral blood samples are taken over 49 days to determine the 24-hour recovery and survival (T50) of the infused RBC.
Intravenous infusion of sham treated autologous erythrocytes. Peripheral blood samples are taken over 49 days to determine the 24-hour recovery and survival (T50) of the infused RBC.
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States
24-hour post transfusion recovery of infused autologous RBCs
The 24-hour recovery of autologous RBCs loaded with DSP or sham using the EDS will be greater than 75% with 95% confidence. For RBC kinetics and recovery will be reported as mean, 2-sided 95% CI on the mean, standard deviation, minimum and maximum.
Time frame: 24 hours
Long-term survival of infused autologous RBCs assessed with T50 (Time to disappearance of 50% of the labelled red blood cells from the circulation)
For RBC T50 will be reported as mean, 2-sided 95% CI on the mean, standard deviation, minimum and maximum.
Time frame: up to 49 days
Special laboratory tests
pH at 37°C, hemolysis, ATP, 2,3-DPG, extracellular potassium, extracellular glucose, extracellular lactate, packed cell volume, RBC morphology and RBC indices. In particular free haemoglobin and and hematuria will be assessed on all defined time points.The measure is a composite outcome
Time frame: up to 49 days
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