Inactivation of Whole Blood With Mirasol

Study Overview
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Brief Summary
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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
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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

Official Title
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Inactivation of Whole Blood With Mirasol : Performance in Red Blood Cells in Healthy Volunteers

Conditions
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Focus of Study: Radiolabel Recovery and Survival of RBCs

Intervention / Treatment
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* Device: Mirasol System for Whole Blood


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: Mirasol-treated WB then untreated WB<br>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 | Device: Mirasol System for Whole Blood<br>* LR-pRBC units derived from WB will be treated with the Mirasol System. Treatment with the Mirasol System requires riboflavin to be mixed into the whole blood unit, which is then exposed to ultra violet (UV) light for a period of time; approximately an hour.<br>* Other names: Pathogen Reduction Technology;|
| Experimental: Arm 2: Untreated WB then Mirasol-treated WB<br>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 | Device: Mirasol System for Whole Blood<br>* LR-pRBC units derived from WB will be treated with the Mirasol System. Treatment with the Mirasol System requires riboflavin to be mixed into the whole blood unit, which is then exposed to ultra violet (UV) light for a period of time; approximately an hour.<br>* Other names: Pathogen Reduction Technology;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Red Blood Cell (RBC) 24-Hour Recovery | 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. | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Red Blood Cell (RBC) Survival by Product | 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. | 28 days | 
| Area Under the Curve (AUC) of Red Blood Cell (RBC) Survival | Assessment of AUC of RBC survival over 28 days for RBCs derived from Mirasol-treated Whole Blood (WB) versus RBCs derived from untreated WB. | 28 days | 
| Spearman's Correlation Coefficients: 24-Hour Red Blood Cell (RBC) Recovery (%) With Hemolysis (%) | 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 | 24 hours | 
| Spearman's Correlation Coefficients: 24-Hour RBC Recovery (%) With Adenosine Triphosphate (ATP) (µmol/g Hgb) | 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 | 24 hours | 
| Spearman's Correlation Coefficients: 24-Hour RBC Recovery (%) pCO2 (mmHg at 37° C) | 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 | 24 hours | 
| Spearman's Correlation Coefficients: Linear T50 (Days) With Hemolysis (%) | 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 | 28 days | 
| Spearman's Correlation Coefficients: Linear T50 (Days) With Adenosine Triphosphate (ATP) (µmol/g Hgb) | 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 | 28 days | 
| Spearman's Correlation Coefficients: Linear T50 (Days) With pCO2 (mmHg at 37° C) | 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 | 28 days | 
| Neoantigenicity - Day 21 Direct Antigen Test (DAT) | 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. | Day 21 | 
| Neoantigenicity - Day 21 Indirect Antigen Test (IAT) | 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. | Day 21 of Treatment Periods 1 and 2 | 
| Neoantigenicity - Day 42 Direct Antigen Test (DAT) | 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. | Day 42 of Treatment Periods 1 and 2 | 
| Neoantigenicity - Day 42 Indirect Antigen Test (IAT) | 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. | Day 42 of Treatment Periods 1 and 2 | 
| In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Hematocrit (%) |  | Day 0 | 
| 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) - ATP |  | Day 0 | 
| 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) - White Blood Cell (WBC) Count |  | Day 0 | 
| 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 0 | 
| 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 0 | 
| 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) - pCO2 (mmHg at 37° C) |  | Day 0 | 
| 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) - Potassium |  | Day 0 | 
| 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 0 | 
| In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Glucose |  | Day 21 | 
| In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Lactate |  | Day 0 | 
| In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Lactate |  | Day 21 | 
| In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Supernatant Hgb |  | Day 0 | 
| In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Supernatant Hgb |  | Day 21 | 
| In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - 2,3-diphosphoglycerate (DPG) |  | Day 0 | 
| In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - 2,3-diphosphoglycerate (DPG) |  | Day 21 | 
| In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Hemolysis (%) |  | Day 0 | 
| In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Hemolysis (%) |  | Day 21 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pathogen reduction technology