Inactivation of Whole Blood With Mirasol

Phase 1

Completed

Conditions: Focus of Study: Radiolabel Recovery and Survival of RBCs

Interventions: Device: Mirasol System for Whole Blood

Registration Number: NCT01907906

Lead Sponsor: Terumo BCTbio

Brief Summary: The purpose of this study is to evaluate radiolabeled recovery and survival of autologous red blood cells (RBC), derived from Mirasol-treated fresh whole blood (WB), stored as leukoreduced packed RBC (LR-pRBC), and re-infused in healthy adult subjects

Detailed Description: This is a feasibility level study conducted to assess the recovery and survival of autologous, radiolabeled leukoreduced packed red blood cells (LR-pRBC) derived from fresh whole blood (WB) units that have been treated with the Mirasol System for Whole Blood (Mirasol System) and stored for 21 days at 1-6°C.1

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 29

Inclusion Criteria

Eligible whole blood donor
Age ≥ 18 years, of either sex
Able to commit to the study follow-up schedule
Subjects must have adequate bilateral antecubital venous access for WB collection and follow-up blood draws
Negative screening test panel for infectious diseases
Subjects of child-bearing potential (female or male) must agree to use effective contraceptive during the course of the study per site guidelines
Subjects must agree to report adverse events (AEs) during the required reporting period
Negative direct antiglobulin test (DAT) with subject's RBC
Negative indirect antiglobulin test (IAT) with subject's serum

Inclusion for radiolabeled reinfusion of LR-pRBC on Day 21 (evaluated the day of, prior to, reinfusion):

Maintenance of healthy status
Negative direct antiglobulin test (DAT) with subject's RBC (fresh)
Negative indirect antiglobulin test (IAT) with subject's serum (fresh) versus autologous stored LR-pRBC
Negative serum or urine pregnancy test in females

Exclusion Criteria

Any serious medical illness and/or therapy, including: abnormal bleeding episodes, clotting or bleeding disorder, evidence of anemia, myocardial infarction, uncontrolled hypertension, heart disease, surgery with bleeding complications, epilepsy or any major surgery (with general or spinal anesthesia) within the last 6 months
Pregnant or nursing females; For women of childbearing potential, negative serum or urine pregnancy tests at the time of WB donation and before the reinfusion are required
Unable to give informed consent
Participation currently, or within the last 12 months, in another investigational trial that would potentially interfere with the analysis of this investigation (e.g., pharmaceutical)
Have received an accumulated radiation dose that would exclude them from the study according to the local radiation safety limits established by each institution
Inability to comply with the protocol in the opinion of the investigator

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Arm 2: Untreated WB then Mirasol-treated WB	Mirasol System for Whole Blood	Screening Period (14 days); Treatment Period 1 (49 days): Donation of WB, UNTREATED on Day 0, LR-pRBCs manufactured \& stored 21 days, radiolabeled RBCs reinfused on Day 21 and samples collected over 28 days (Days 21-49); WB Donation Deferral Period (35-49 days); Treatment Period 2 (49 days): Donation of WB treated with Mirasol System for Whole Blood on Day 0, LR-pRBCs manufactured \& stored 21 days, radiolabeled RBCs reinfused on Day 21 and samples collected over 28 days (Days 21-49) Study Exit on Treatment Period 2, Day 49
Arm 1: Mirasol-treated WB then untreated WB	Mirasol System for Whole Blood	Screening Period (14 days); Treatment Period 1 (49 days): Donation of WB treated with Mirasol System for Whole Blood on Day 0, LR-pRBCs manufactured \& stored 21 days, radiolabeled RBCs reinfused on Day 21 and samples collected over 28 days (Days 21-49); WB Donation Deferral Period (35-49 days); Treatment Period 2 (49 days): Donation of WB, UNTREATED on Day 0, LR-pRBCs manufactured \& stored 21 days, radiolabeled RBCs reinfused on Day 21 and samples collected over 28 days (Days 21-49) Study Exit on Treatment Period 2, Day 49

Primary Outcome Measures

Name	Time	Method
Red Blood Cell (RBC) 24-Hour Recovery	24 hours	To evaluate, as per FDA criteria, the 24-hour post transfusion RBC recovery in healthy adult subjects of leuko-reduced packed red blood cells (LR-pRBC) that have been derived from Mirasol-treated fresh WB units and stored at 1 to 6°C for 21 days. 24-hour RBC Recovery is a measure of the % of RBCs that are still functioning 24 hours after they have been reinfused back into the donor following storage over 21 days.

Secondary Outcome Measures

Name	Time	Method
Spearman's Correlation Coefficients: 24-Hour RBC Recovery (%) With Adenosine Triphosphate (ATP) (µmol/g Hgb)	24 hours	Spearman's Correlation Coefficients comparing 24-Hour RBC Recovery (%) with ATP (µmol/g Hgb) in packed Red Blood Cells (pRBCs) derived from Mirasol-treated whole blood (WB) versus pRBCs derived from untreated WB
Spearman's Correlation Coefficients: 24-Hour RBC Recovery (%) pCO2 (mmHg at 37° C)	24 hours	Spearman's Correlation Coefficients comparing 24-Hour RBC Recovery (%) with pCO2 (mmHg at 37° C) in packed Red Blood Cells (pRBCs) derived from Mirasol-treated whole blood (WB) versus pRBCs derived from untreated WB
Spearman's Correlation Coefficients: Linear T50 (Days) With Hemolysis (%)	28 days	Spearman's Correlation Coefficients comparing Linear T50 (Days) with each of Hemolysis (%) in packed Red Blood Cells (pRBCs) derived from Mirasol-treated whole blood (WB) versus pRBCs derived from untreated WB
In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Hematocrit (%)	Day 21
In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Hemolysis (%)	Day 21
Red Blood Cell (RBC) Survival by Product	28 days	Assessment of linear \& exponential RBC survival and half-life (T50) over 28 days for RBCs derived from Mirasol-treated WB versus RBCs derived from untreated WB.
Neoantigenicity - Day 21 Direct Antigen Test (DAT)	Day 21	DAT testing of Red Blood Cells (RBCs) via Anti-immunoglobulin G (Anti-IgG) and Anti Complement Component 3 (Anti-C3) as derived from Mirasol-treated whole blood (WB) versus untreated WB conducted on Day 21 of both Treatment Periods 1 and 2. Number of positive results (indicating a new antigen formation) were recorded.
Neoantigenicity - Day 42 Direct Antigen Test (DAT)	Day 42 of Treatment Periods 1 and 2	DAT testing of RBCs via Anti-IgG and Anti-C3 as derived from Mirasol-treated WB versus untreated WB. Number of positive results (indicating a new antigen formation) were recorded.
In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - White Blood Cell (WBC) Count	Day 21
In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Total Hemoglobin	Day 21
In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - pH (at 37° C)	Day 21
In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Potassium	Day 21
In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Glucose	Day 21
Area Under the Curve (AUC) of Red Blood Cell (RBC) Survival	28 days	Assessment of AUC of RBC survival over 28 days for RBCs derived from Mirasol-treated Whole Blood (WB) versus RBCs derived from untreated WB.
Spearman's Correlation Coefficients: Linear T50 (Days) With pCO2 (mmHg at 37° C)	28 days	Spearman's Correlation Coefficients comparing Linear T50 (Days) with pCO2 (mmHg at 37° C) in packed Red Blood Cells (pRBCs) derived from Mirasol-treated whole blood (WB) versus pRBCs derived from untreated WB
Neoantigenicity - Day 42 Indirect Antigen Test (IAT)	Day 42 of Treatment Periods 1 and 2	IAT testing of RBCs via low ionic strength solution (LISS-15), Anti-IgG and C3 as derived from Mirasol-treated WB versus untreated WB. Number of positive results (indicating antibody formation to a new antigen) were recorded.
In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - ATP	Day 21
In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - 2,3-diphosphoglycerate (DPG)	Day 21
Spearman's Correlation Coefficients: 24-Hour Red Blood Cell (RBC) Recovery (%) With Hemolysis (%)	24 hours	Spearman's Correlation Coefficients comparing 24-Hour RBC Recovery (%) with Hemolysis (%) in packed Red Blood Cells (pRBCs) derived from Mirasol-treated whole blood (WB) versus pRBCs derived from untreated WB
Spearman's Correlation Coefficients: Linear T50 (Days) With Adenosine Triphosphate (ATP) (µmol/g Hgb)	28 days	Spearman's Correlation Coefficients comparing Linear T50 (Days) with ATP (µmol/g Hgb) in packed Red Blood Cells (pRBCs) derived from Mirasol-treated whole blood (WB) versus pRBCs derived from untreated WB
In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - pCO2 (mmHg at 37° C)	Day 21
In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Lactate	Day 21
Neoantigenicity - Day 21 Indirect Antigen Test (IAT)	Day 21 of Treatment Periods 1 and 2	Day 21 IAT testing of RBCs via LISS-15, Anti-IgG and C3 as derived from Mirasol-treated WB versus untreated WB. Number of positive results (indicating antibody formation to a new antigen) were recorded.
In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Supernatant Hgb	Day 21