Inactivation of Whole Blood With Mirasol (IMPROVEII)

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

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

Study Overview

• Status: Completed
• Conditions: Focus of Study: Radiolabel Recovery and Survival of RBCs
• Intervention / Treatment: Device: Mirasol System for Whole Blood

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

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Hoxworth Blood Center
  • Washington
    • Seattle, Washington, United States, 98104
      • Puget Sound Blood Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: Mirasol-treated WB then untreated WB; 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; 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.; Other Names: Pathogen Reduction Technology
Experimental: Arm 2: Untreated WB then Mirasol-treated WB; 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; 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.; Other Names: Pathogen Reduction Technology

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Terumo BCTbio
• Collaborators: U.S. Army Medical Research and Development Command
• Investigators: Study Director: Raymond P Goodrich, PhD, TerumoBCT Biotechnologies

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: June 20, 2013
• First Submitted That Met QC Criteria: July 22, 2013
• First Posted (Estimate): July 25, 2013

Study Record Updates

• Last Update Posted (Estimate): August 18, 2015
• Last Update Submitted That Met QC Criteria: July 28, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: Pathogen reduction technology
• Other Study ID Numbers: CTS-0080; ERMS#12308001 (Other Grant/Funding Number: Department of Defense)