Healthy Volunteer Red Blood Cell Labeling Study; Not Disease Focused
Conditions
Keywords
Healthy volunteers, Red blood cell labeling
Brief summary
This research is being done to compare the red blood circulation survival in healthy adult volunteers between the 51 chromium (51Cr) red blood cell (RBC) labeling method and the Biotin (BioRBC) red blood cell (RBC) labeling method to determine if biotinylated red blood cells (BioRBC) is an acceptable non radioactive alternative to 51 chromium (51Cr) radiolabeling for regulatory pharmacokinetic studies of red blood cell products.
Detailed description
This is a Phase 1, randomized, controlled, autologous transfusion study in healthy adult volunteers designed to compare biotinylated red blood cells (BioRBC) with 51 chromium (51Cr)-labeled red blood cells for the assessment of red blood cell (RBC) recovery and survival after 42 days of storage, with and without irradiation at Day 0. Both 51Cr and biotin labeling have been used to measure autologous RBC recovery and survival, but biotin has not yet been accepted by the U.S. Food and Drug Administration (FDA) as a method to determine 24 hour post transfusion recovery and long term survival after storage. Study procedures include screening, blood samples, testing, labeling and transfusion. It is expected that about 20 people will take part in this research study.
Interventions
BIOLOGICALBiotinylated Red Blood Cells (BioRBC)
Intravenous infusion
BIOLOGICALIrradiated Biotinylated Red Blood Cells (Irradiated BioRBC)
Intravenous infusion
BIOLOGICAL51 Chromium Labeled Red Blood Cells (51Cr RBC)
Intravenous infusion
BIOLOGICALTechnetium 99m Labeled Red Blood Cells (99mTc RBC)
Intravenous infusion
Sponsors
Jose Cancelas
Department of Health and Human Services
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Signed and dated informed consent form. * Age ≥18 years, of either gender. * Normal health status (as determined by Investigators' review of medical history and physical exam). * Qualifies for a collection; Males: height \>5'1" and weight \>130 lbs; Females: height \>5' 5" and weight \> 150 lbs. * Complete blood count (CBC; including RBC indices MCV, MCH, MCHC, and RDW) and serum chemistry values within normal limits (including calcium, bicarbonate, chloride, inorganic phosphate, potassium, sodium, cholesterol, glucose, total protein, triglycerides, LDH, ALT, AST, total bilirubin, BUN, creatinine, and ferritin). Values outside of normal reference range if considered not to be clinically significant by the site PI may be allowed as per the site PI. * Hemoglobin levels \>13.3 g/dL and hematocrit \>40% for both male and female subjects. * Negative blood donor screening test panel for HIV, HBV, HCV, HTLV, Syphilis, and WNV virus at the time of donation. * Female subjects of childbearing potential and male subjects must agree to use a medically acceptable method of contraception throughout the study periods. A barrier method of contraception must be included, regardless of other methods. * Meet or exceed AABB guidelines for blood donation, with the exception of travel deferrals as defined by site-specific SOPs.
Exclusion criteria
* Known RBC disorder that could affect RBC survival. * Treatment with any medication known to affect RBC viability. * Pregnant or nursing female. * Male subjects or female subjects of childbearing potential not using medically acceptable contraceptive methods. * Participation in another clinical study currently or within the past 28 days. * Subjects not eligible to provide a double RBC donation per AABB guidelines for blood donation. * Subjects who have received blood transfusion within the previous year. * Known pre-existing antibody specific to BioRBC. * Subjects who have received a previous infusion of BioRBC at any time.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 24-hour Post-transfusion Recovery (PTR24) of Irradiated or Non-irradiated biotinylated Red Blood Cells Compared With 51Cr-Labeled Red Blood Cells | Day 1 after completion of autologous RBC infusion (Day 43 of the study) | Percentage of infused autologous red blood cells (RBC) remaining in circulation 24 hours after transfusion |
| Lifespan of of Irradiated or Non-irradiated biotinylated Red Blood Cells Compared With 51Cr-Labeled Red Blood Cells | From immediately post infusion through Day 112 post-infusion (day 154 of the study, at approximately 16 weeks post transfusion). | Survival of autologous irradiated RBC expressed as days of RBC present in blood until they disappear from circulation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| T50 of Irradiated or Non-irradiated biotinylated Red Blood Cells Compared With 51Cr-Labeled Red Blood Cells | From immediately post infusion through Day 112 post-infusion (day 154 of the study, at approximately 16 weeks post transfusion). | Lifespan of autologous irradiated RBC, expressed as Median lifespan (T50; time in days for 50% of labeled red cells remain in circulation) |
| Area under the curve (AUC) of Irradiated or Non-irradiated biotinylated Red Blood Cells Compared With 51Cr-Labeled Red Blood Cells | From immediately post infusion through Day 112 post-infusion (day 154 of the study, at approximately 16 weeks post transfusion). | Area under the curve of autologous irradiated RBC, expressed as an integrated area of the parameter time (days) x percentage of remaining cells in circulation |
| Incidence of Adverse Events and Serious Adverse Events Following Infusion of Biotinylated and Irradiated Biotinylated Red Blood Cells | From Day 42 (infusion day) through Day 154 (approximately 16 weeks post transfusion) | Number and proportion of subjects experiencing adverse events (AEs) and serious adverse events (SAEs) with specific attention to: * Infusion reactions (e.g., fever, chills, rash, hypotension), Suspected transfusion related sepsis, Events meeting protocol defined stopping rules (e.g., hemolysis with anti BioRBC antibody), and Any AE judged possibly, probably, or definitely related to infusion of BioRBC or irradiated BioRBC. |
| Incidence of Antibodies Against Biotinylated Red Blood Cells After Infusion of BioRBC | From screening (up to 28 days before donation) through Day 112 post infusion (day 154 after red blood cell collection); extended follow up annually if anti BioRBC is detected until it disappears from circulation. | Proportion of subjects who develop detectable antibodies specific to biotinylated RBC (anti BioRBC) following infusion of BioRBC |
Countries
United States
Contacts
CONTACTJose A Cancelas-Perez, MD, PhD
PRINCIPAL_INVESTIGATORJose A Cancelas-Perez, MD, PhD
Dana-Farber Cancer Institute
Outcome results
None listed