IMPROVEII: Inactivation of Whole Blood With Mirasol

• Sponsor: Terumo BCTbio (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01907906
• Collaborator: U.S. Army Medical Research and Development Command (U.S. Fed)
• Enrollment: 29
• Locations: 2
• Arms: 2
• Duration (Months): 11
• Patients Per Site: 14.5
• Patients Per Site Per Month: 1.3

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Focus of Study: Radiolabel Recovery and Survival of RBCs	Device: Mirasol System for Whole Blood	Phase 1

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 Design

• Study Type: Interventional
• Actual Enrollment: 29 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Inactivation of Whole Blood With Mirasol : Performance in Red Blood Cells in Healthy Volunteers
• Study Start Date: Jun 1, 2013
• Actual Primary Completion Date: May 1, 2014
• Actual Study Completion Date: May 1, 2014

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

2. 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.

3. 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

4. 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

5. 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

6. 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

7. 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

8. 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

9. 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.

10. 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.

11. 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.

12. 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.

13. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Hematocrit (%) [Day 0]

14. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Hematocrit (%) [Day 21]

15. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - ATP [Day 0]

16. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - ATP [Day 21]

17. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - White Blood Cell (WBC) Count [Day 0]

18. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - White Blood Cell (WBC) Count [Day 21]

19. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Total Hemoglobin [Day 0]

20. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Total Hemoglobin [Day 21]

21. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - pH (at 37° C) [Day 0]

22. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - pH (at 37° C) [Day 21]

23. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - pCO2 (mmHg at 37° C) [Day 0]

24. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - pCO2 (mmHg at 37° C) [Day 21]

25. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Potassium [Day 0]

26. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Potassium [Day 21]

27. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Glucose [Day 0]

28. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Glucose [Day 21]

29. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Lactate [Day 0]

30. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Lactate [Day 21]

31. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Supernatant Hgb [Day 0]

32. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Supernatant Hgb [Day 21]

33. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - 2,3-diphosphoglycerate (DPG) [Day 0]

34. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - 2,3-diphosphoglycerate (DPG) [Day 21]

35. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Hemolysis (%) [Day 0]

36. In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Hemolysis (%) [Day 21]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hoxworth Blood Center	Cincinnati	Ohio	United States	45267
2	Puget Sound Blood Center	Seattle	Washington	United States	98104

Sponsors and Collaborators

• Terumo BCTbio
• U.S. Army Medical Research and Development Command

Investigators

• Study Director: Raymond P Goodrich, PhD, TerumoBCT Biotechnologies

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Terumo BCTbio
• ClinicalTrials.gov Identifier: NCT01907906
• Other Study ID Numbers: CTS-0080; ERMS#12308001
• First Posted: Jul 25, 2013
• Last Update Posted: Aug 18, 2015
• Last Verified: Jul 1, 2015

• Keywords provided by Terumo BCTbio: Pathogen reduction technology

Study Results

Participant Flow

Arm/Group Title	Arm 1: Mirasol-treated Whole Blood (WB) Then Untreated WB	Arm 2: Untreated WB Then Mirasol-treated WB
Arm/Group Description	Screening Period (14 days); Treatment Period 1 (49 days): Donation of WB treated with Mirasol System for Whole Blood on Day 0, leuko-reduced packed red blood cells (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	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
Period Title: Overall Study
STARTED	16	13
COMPLETED	12	12
NOT COMPLETED	4	1

Baseline Characteristics

Arm/Group Title	Arm 1: Mirasol-treated WB Then Untreated WB	Arm 2: Untreated WB Then Mirasol-treated WB	Total
Arm/Group Description	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	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)	Total of all reporting groups
Overall Participants	16	13	29
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	15 93.8%	13 100%	28 96.6%
>=65 years	1 6.3%	0 0%	1 3.4%
Sex: Female, Male (Count of Participants)
Female	2 12.5%	6 46.2%	8 27.6%
Male	14 87.5%	7 53.8%	21 72.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	1 7.7%	1 3.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	16 100%	11 84.6%	27 93.1%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 7.7%	1 3.4%
Region of Enrollment (participants) [Number]
United States	16 100%	13 100%	29 100%

Outcome Measures

1. Primary Outcome

Title	Red Blood Cell (RBC) 24-Hour Recovery
Description	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.
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

All subjects who signed an IC form (were enrolled), met eligibility criteria, had no intercurrent illness or notable signs/symptoms during the 24 hours prior to reinfusion, had no evidence of neoantigen formation on stored LR-pRBCs, and had at least 4 blood samples collected during the first 22 min, 30 sec post-infusion in each treatment period.

Arm/Group Title	Mirasol Treated	Untreated Control
Arm/Group Description	LR-pRBCs derived from Mirasol-treated WB	LR-pRBCs derived from untreated WB
Measure Participants	24	24
Mean (Standard Deviation) [% 24-hour RBC Recovery]	82.51 (3.914)	91.70 (6.812)

2. Secondary Outcome

Title	Red Blood Cell (RBC) Survival by Product
Description	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.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

All subjects who signed informed consent,were eligible, had no intercurrent illness or notable signs/symptoms in 24 hrs prior to reinfusion, had no evidence of neoantigen formation on stored LR-pRBCs, and had ≥ 4 blood samples collected within the first 22 min 30 sec post-infusion in each treatment period.

Arm/Group Title	Mirasol Treated	Untreated Control
Arm/Group Description	LR-pRBCs derived from Mirasol-treated WB	LR-pRBCs derived from untreated WB
Measure Participants	24	24
Linear RBC Survival	60.49 (5.574)	81.57 (15.474)
Linear T50	22.58 (4.328)	35.83 (7.863)
Exponential RBC Survival	46.71 (5.630)	67.81 (15.492)
Exponential T50	22.63 (5.286)	39.91 (10.485)

3. Secondary Outcome

Title	Area Under the Curve (AUC) of Red Blood Cell (RBC) Survival
Description	Assessment of AUC of RBC survival over 28 days for RBCs derived from Mirasol-treated Whole Blood (WB) versus RBCs derived from untreated WB.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

All subjects who signed an IC Form (were enrolled), met eligibility criteria, had no intercurrent illness or notable signs/symptoms during the 24 hours prior to reinfusion, had no evidence of neoantigen formation on stored LR-pRBCs, and had at least 4 blood samples collected within the first 22 min, 30 sec post-infusion in each treatment period.

Arm/Group Title	Mirasol Treated	Untreated Control
Arm/Group Description	LR-pRBCs derived from Mirasol-treated WB	LR-pRBCs derived from untreated WB
Measure Participants	24	24
Mean (Standard Deviation) [Days * Percent Recovery]	1715.2 (173.13)	2055.2 (158.34)

4. Secondary Outcome

Title	Spearman's Correlation Coefficients: 24-Hour Red Blood Cell (RBC) Recovery (%) With Hemolysis (%)
Description	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
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

All subjects who signed an IC Form (were enrolled), met eligibility criteria, had no intercurrent illness or notable signs/symptoms during the 24 hours prior to reinfusion, had no evidence of neoantigen formation on stored LR-pRBCs, and had at least 4 blood samples collected within the first 22 min, 30 sec post-infusion in each treatment period.

Arm/Group Title	Mirasol Treated	Untreated Control
Arm/Group Description	LR-pRBCs derived from Mirasol-treated WB	LR-pRBCs derived from untreated WB
Measure Participants	24	24
Number [Spearman's Correlation Coefficient]	-0.1779	0.4286

5. Secondary Outcome

Title	Spearman's Correlation Coefficients: 24-Hour RBC Recovery (%) With Adenosine Triphosphate (ATP) (µmol/g Hgb)
Description	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
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

All subjects who signed an IC Form (were enrolled), met eligibility criteria, had no intercurrent illness or notable signs/symptoms during the 24 hours prior to reinfusion, had no evidence of neoantigen formation on stored LR-pRBCs, and had at least 4 blood samples collected within the first 22 min, 30 sec post-infusion in each treatment period.

Arm/Group Title	Mirasol Treated	Untreated Control
Arm/Group Description	LR-pRBCs derived from Mirasol-treated WB	LR-pRBCs derived from untreated WB
Measure Participants	24	24
Number [Spearman's Correlation Coefficient]	0.6107	0.4116

6. Secondary Outcome

Title	Spearman's Correlation Coefficients: 24-Hour RBC Recovery (%) pCO2 (mmHg at 37° C)
Description	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
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

All subjects who signed an IC Form (were enrolled), met eligibility criteria, had no intercurrent illness or notable signs/symptoms during the 24 hours prior to reinfusion, had no evidence of neoantigen formation on stored LR-pRBCs, and had at least 4 blood samples collected within the first 22 min, 30 sec post-infusion in each treatment period.

Arm/Group Title	Mirasol Treated	Untreated Control
Arm/Group Description	LR-pRBCs derived from Mirasol-treated WB	LR-pRBCs derived from untreated WB
Measure Participants	24	24
Number [Spearman's Correlation Coefficient]	0.0383	0.0475

7. Secondary Outcome

Title	Spearman's Correlation Coefficients: Linear T50 (Days) With Hemolysis (%)
Description	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
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

All subjects who signed an IC Form (were enrolled), met eligibility criteria, had no intercurrent illness or notable signs/symptoms during the 24 hours prior to reinfusion, had no evidence of neoantigen formation on stored LR-pRBCs, and had at least 4 blood samples collected within the first 22 min, 30 sec post-infusion in each treatment period.

Arm/Group Title	Mirasol Treated	Untreated Control
Arm/Group Description	LR-pRBCs derived from Mirasol-treated WB	LR-pRBCs derived from untreated WB
Measure Participants	24	24
Number [Spearman's Correlation Coefficient]	-0.0592	0.0564

8. Secondary Outcome

Title	Spearman's Correlation Coefficients: Linear T50 (Days) With Adenosine Triphosphate (ATP) (µmol/g Hgb)
Description	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
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

All subjects who signed an IC Form (were enrolled), met eligibility criteria, had no intercurrent illness or notable signs/symptoms during the 24 hours prior to reinfusion, had no evidence of neoantigen formation on stored LR-pRBCs, and had at least 4 blood samples collected within the first 22 min, 30 sec post-infusion in each treatment period.

Arm/Group Title	Mirasol Treated	Untreated Control
Arm/Group Description	LR-pRBCs derived from Mirasol-treated WB	LR-pRBCs derived from untreated WB
Measure Participants	24	24
Number [Spearman's Correlation Coefficient]	0.2487	0.0261

9. Secondary Outcome

Title	Spearman's Correlation Coefficients: Linear T50 (Days) With pCO2 (mmHg at 37° C)
Description	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
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

All subjects who signed an IC Form (were enrolled), met eligibility criteria, had no intercurrent illness or notable signs/symptoms during the 24 hours prior to reinfusion, had no evidence of neoantigen formation on stored LR-pRBCs, and had at least 4 blood samples collected within the first 22 min, 30 sec post-infusion in each treatment period.

Arm/Group Title	Mirasol Treated	Untreated Control
Arm/Group Description	LR-pRBCs derived from Mirasol-treated WB	LR-pRBCs derived from untreated WB
Measure Participants	24	24
Number [Spearman's Correlation Coefficient]	-0.0691	-0.1065

10. Secondary Outcome

Title	Neoantigenicity - Day 21 Direct Antigen Test (DAT)
Description	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.
Time Frame	Day 21

Outcome Measure Data

Analysis Population Description

All subjects who signed an IC Form (were enrolled), and had samples available for the requested test on Day 21 of both Treatment Periods 1 and 2

Arm/Group Title	Mirasol Treated	Untreated Control
Arm/Group Description	Leuko-Reduced packed Red Blood Cells (LR-pRBCs) derived from Mirasol-treated WB	Leuko-Reduced packed Red Blood Cells (LR-pRBCs) derived from untreated WB
Measure Participants	24	23
Number [Positive results]	0	0

11. Secondary Outcome

Title	Neoantigenicity - Day 21 Indirect Antigen Test (IAT)
Description	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.
Time Frame	Day 21 of Treatment Periods 1 and 2

Outcome Measure Data

Analysis Population Description

All subjects who signed an IC Form (were enrolled), and had samples available for the requested test on Day 21 of both Treatment Periods 1 and 2

Arm/Group Title	Mirasol Treated	Untreated Control
Arm/Group Description	LR-pRBCs derived from Mirasol-treated WB	LR-pRBCs derived from untreated WB
Measure Participants	24	23
Number [Positive results]	0	0

12. Secondary Outcome

Title	Neoantigenicity - Day 42 Direct Antigen Test (DAT)
Description	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.
Time Frame	Day 42 of Treatment Periods 1 and 2

Outcome Measure Data

Analysis Population Description

All subjects who signed an IC Form (were enrolled), and had samples available for the requested test

Arm/Group Title	Mirasol Treated	Untreated Control
Arm/Group Description	LR-pRBCs derived from Mirasol-treated WB	LR-pRBCs derived from untreated WB
Measure Participants	23	24
Number [Positive results]	0	0

13. Secondary Outcome

Title	Neoantigenicity - Day 42 Indirect Antigen Test (IAT)
Description	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.
Time Frame	Day 42 of Treatment Periods 1 and 2

Outcome Measure Data

Analysis Population Description

All subjects who signed an IC Form (were enrolled), and had samples available for the requested test on Day 42 of both Treatment Periods 1 and 2.

Arm/Group Title	Mirasol Treated	Untreated Control
Arm/Group Description	LR-pRBCs derived from Mirasol-treated WB	LR-pRBCs derived from untreated WB
Measure Participants	24	24
Number [Positive results]	0	0

14. Secondary Outcome

Title	In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Hematocrit (%)
Time Frame	Day 0

Outcome Measure Data

Analysis Population Description

All subjects who signed an IC Form (were enrolled), and had samples available for the requested test

Arm/Group Title	Mirasol Treated	Untreated Control
Arm/Group Description	LR-pRBCs derived from Mirasol-treated WB	LR-pRBCs derived from untreated WB
Measure Participants	26	24
Mean (Standard Deviation) [% of volume]	59.2 (2.83)	61.0 (3.21)

15. Secondary Outcome

Title	In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Hematocrit (%)
Time Frame	Day 21

Outcome Measure Data

Analysis Population Description

All subjects who signed an IC Form (were enrolled), and had samples available for the requested test

Arm/Group Title	Mirasol Treated	Untreated Control
Arm/Group Description	LR-pRBCs derived from Mirasol-treated WB	LR-pRBCs derived from untreated WB
Measure Participants	25	24
Mean (Standard Deviation) [volume % of red blood cells]	58.3 (2.59)	60.5 (2.65)

16. Secondary Outcome

Title	In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - ATP
Time Frame	Day 0

Outcome Measure Data

Analysis Population Description

All subjects who signed an IC Form (were enrolled), and had samples available for the requested test

Arm/Group Title	Mirasol Treated	Untreated Control
Arm/Group Description	LR-pRBCs derived from Mirasol-treated WB	LR-pRBCs derived from untreated WB
Measure Participants	24	24
Mean (Standard Deviation) [µmol/g Hgb]	4.659 (0.7372)	4.544 (0.4275)

17. Secondary Outcome

Title	In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - ATP
Time Frame	Day 21

Outcome Measure Data

Analysis Population Description

All subjects who signed an IC Form (were enrolled), and had samples available for the requested test

Arm/Group Title	Mirasol Treated	Untreated Control
Arm/Group Description	LR-pRBCs derived from Mirasol-treated WB	LR-pRBCs derived from untreated WB
Measure Participants	24	24
Mean (Standard Deviation) [µmol/g Hgb]	4.416 (1.1313)	5.403 (1.0111)

18. Secondary Outcome

Title	In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - White Blood Cell (WBC) Count
Time Frame	Day 0

Outcome Measure Data

Analysis Population Description

All subjects who signed an IC Form (were enrolled), and had samples available for the requested test

Arm/Group Title	Mirasol Treated	Untreated Control
Arm/Group Description	LR-pRBCs derived from Mirasol-treated WB	LR-pRBCs derived from untreated WB
Measure Participants	26	24
Mean (Standard Deviation) [10E3 cells/µL]	0.004 (0.0196)	0.000 (0.0000)

19. Secondary Outcome

Title	In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - White Blood Cell (WBC) Count
Time Frame	Day 21

Outcome Measure Data

Analysis Population Description

All subjects who signed an IC Form (were enrolled), and had samples available for the requested test

Arm/Group Title	Mirasol Treated	Untreated Control
Arm/Group Description	LR-pRBCs derived from Mirasol-treated WB	LR-pRBCs derived from untreated WB
Measure Participants	25	24
Mean (Standard Deviation) [10E3 cells/µL]	0.004 (0.0200)	0.021 (0.0833)

20. Secondary Outcome

Title	In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Total Hemoglobin
Time Frame	Day 0

Outcome Measure Data

Analysis Population Description

All subjects who signed an IC Form (were enrolled), and had samples available for the requested test

Arm/Group Title	Mirasol Treated	Untreated Control
Arm/Group Description	LR-pRBCs derived from Mirasol-treated WB	LR-pRBCs derived from untreated WB
Measure Participants	26	24
Mean (Standard Deviation) [g/dL]	19.4 (1.125)	20.04 (1.222)

21. Secondary Outcome

Title	In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Total Hemoglobin
Time Frame	Day 21

Outcome Measure Data

Analysis Population Description

All subjects who signed an IC Form (were enrolled), and had samples available for the requested test

Arm/Group Title	Mirasol Treated	Untreated Control
Arm/Group Description	LR-pRBCs derived from Mirasol-treated WB	LR-pRBCs derived from untreated WB
Measure Participants	25	24
Mean (Standard Deviation) [g/dL]	19.26 (1.098)	19.90 (1.097)

22. Secondary Outcome

Title	In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - pH (at 37° C)
Time Frame	Day 0

Outcome Measure Data

Analysis Population Description

All subjects who signed an IC Form (were enrolled), and had samples available for the requested test

Arm/Group Title	Mirasol Treated	Untreated Control
Arm/Group Description	LR-pRBCs derived from Mirasol-treated WB	LR-pRBCs derived from untreated WB
Measure Participants	26	24
Mean (Standard Deviation) [pH (at 37° C)]	6.8070 (0.03101)	6.8253 (0.4117)

23. Secondary Outcome

Title	In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - pH (at 37° C)
Time Frame	Day 21

Outcome Measure Data

Analysis Population Description

All subjects who signed an IC Form (were enrolled), and had samples available for the requested test

Arm/Group Title	Mirasol Treated	Untreated Control
Arm/Group Description	LR-pRBCs derived from Mirasol-treated WB	LR-pRBCs derived from untreated WB
Measure Participants	25	24
Mean (Standard Deviation) [pH]	6.5537 (0.04776)	6.5662 (0.04751)

24. Secondary Outcome

Title	In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - pCO2 (mmHg at 37° C)
Time Frame	Day 0

Outcome Measure Data

Analysis Population Description

All subjects who signed an IC Form (were enrolled), and had samples available for the requested test

Arm/Group Title	Mirasol Treated	Untreated Control
Arm/Group Description	LR-pRBCs derived from Mirasol-treated WB	LR-pRBCs derived from untreated WB
Measure Participants	26	24
Mean (Standard Deviation) [pCO2 (mmHg at 37° C)]	59.16 (5.824)	66.71 (6.607)

25. Secondary Outcome

Title	In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - pCO2 (mmHg at 37° C)
Time Frame	Day 21

Outcome Measure Data

Analysis Population Description

All subjects who signed an IC Form (were enrolled), and had samples available for the requested test

Arm/Group Title	Mirasol Treated	Untreated Control
Arm/Group Description	LR-pRBCs derived from Mirasol-treated WB	LR-pRBCs derived from untreated WB
Measure Participants	25	24
Mean (Standard Deviation) [mmHg at 37° C]	93.09 (11.003)	98.43 (10.438)

26. Secondary Outcome

Title	In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Potassium
Time Frame	Day 0

Outcome Measure Data

Analysis Population Description

All subjects who signed an IC Form (were enrolled), and had samples available for the requested test

Arm/Group Title	Mirasol Treated	Untreated Control
Arm/Group Description	LR-pRBCs derived from Mirasol-treated WB	LR-pRBCs derived from untreated WB
Measure Participants	26	24
Mean (Standard Deviation) [mEq/L]	2.17 (0.497)	1.78 (0.465)

27. Secondary Outcome

Title	In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Potassium
Time Frame	Day 21

Outcome Measure Data

Analysis Population Description

All subjects who signed an IC Form (were enrolled), and had samples available for the requested test

Arm/Group Title	Mirasol Treated	Untreated Control
Arm/Group Description	LR-pRBCs derived from Mirasol-treated WB	LR-pRBCs derived from untreated WB
Measure Participants	24	24
Mean (Standard Deviation) [mEq/L]	65.50 (2.497)	36.73 (3.749)

28. Secondary Outcome

Title	In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Glucose
Time Frame	Day 0

Outcome Measure Data

Analysis Population Description

All subjects who signed an IC Form (were enrolled), and had samples available for the requested test

Arm/Group Title	Mirasol Treated	Untreated Control
Arm/Group Description	LR-pRBCs derived from Mirasol-treated WB	LR-pRBCs derived from untreated WB
Measure Participants	26	24
Mean (Standard Deviation) [mg/dL]	560.3 (17.62)	559.5 (45.88)

29. Secondary Outcome

Title	In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Glucose
Time Frame	Day 21

Outcome Measure Data

Analysis Population Description

All subjects who signed an IC Form (were enrolled), and had samples available for the requested test

Arm/Group Title	Mirasol Treated	Untreated Control
Arm/Group Description	LR-pRBCs derived from Mirasol-treated WB	LR-pRBCs derived from untreated WB
Measure Participants	24	24
Mean (Standard Deviation) [mg/dL]	408.5 (30.90)	398.6 (33.84)

30. Secondary Outcome

Title	In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Lactate
Time Frame	Day 0

Outcome Measure Data

Analysis Population Description

All subjects who signed an IC Form (were enrolled), and had samples available for the requested test

Arm/Group Title	Mirasol Treated	Untreated Control
Arm/Group Description	LR-pRBCs derived from Mirasol-treated WB	LR-pRBCs derived from untreated WB
Measure Participants	26	24
Mean (Standard Deviation) [mmol/L]	2.39 (0.623)	2.03 (0.561)

31. Secondary Outcome

Title	In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Lactate
Time Frame	Day 21

Outcome Measure Data

Analysis Population Description

All subjects who signed an IC Form (were enrolled), and had samples available for the requested test

Arm/Group Title	Mirasol Treated	Untreated Control
Arm/Group Description	LR-pRBCs derived from Mirasol-treated WB	LR-pRBCs derived from untreated WB
Measure Participants	24	24
Mean (Standard Deviation) [mmol/L]	17.54 (2.305)	20.34 (3.092)

32. Secondary Outcome

Title	In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Supernatant Hgb
Time Frame	Day 0

Outcome Measure Data

Analysis Population Description

All subjects who signed an IC Form (were enrolled), and had samples available for the requested test

Arm/Group Title	Mirasol Treated	Untreated Control
Arm/Group Description	LR-pRBCs derived from Mirasol-treated WB	LR-pRBCs derived from untreated WB
Measure Participants	24	24
Mean (Standard Deviation) [mg/dL]	49.2 (16.66)	47.1 (17.06)

33. Secondary Outcome

Title	In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Supernatant Hgb
Time Frame	Day 21

Outcome Measure Data

Analysis Population Description

All subjects who signed an IC Form (were enrolled), and had samples available for the requested test

Arm/Group Title	Mirasol Treated	Untreated Control
Arm/Group Description	LR-pRBCs derived from Mirasol-treated WB	LR-pRBCs derived from untreated WB
Measure Participants	24	24
Mean (Standard Deviation) [mg/dL]	99.6 (47.41)	76.7 (34.60)

34. Secondary Outcome

Title	In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - 2,3-diphosphoglycerate (DPG)
Time Frame	Day 0

Outcome Measure Data

Analysis Population Description

All subjects who signed an IC Form (were enrolled), and had samples available for the requested test

Arm/Group Title	Mirasol Treated	Untreated Control
Arm/Group Description	LR-pRBCs derived from Mirasol-treated WB	LR-pRBCs derived from untreated WB
Measure Participants	24	24
Mean (Standard Deviation) [µmol/mL]	12.289 (2.1394)	12.499 (3.7456)

35. Secondary Outcome

Title	In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - 2,3-diphosphoglycerate (DPG)
Time Frame	Day 21

Outcome Measure Data

Analysis Population Description

All subjects who signed an IC Form (were enrolled), and had samples available for the requested test

Arm/Group Title	Mirasol Treated	Untreated Control
Arm/Group Description	LR-pRBCs derived from Mirasol-treated WB	LR-pRBCs derived from untreated WB
Measure Participants	24	24
Mean (Standard Deviation) [µmol/mL]	0.248 (0.2604)	0.333 (0.4146)

36. Secondary Outcome

Title	In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Hemolysis (%)
Time Frame	Day 0

Outcome Measure Data

Analysis Population Description

All subjects who signed an IC Form (were enrolled), and had samples available for the requested test

Arm/Group Title	Mirasol Treated	Untreated Control
Arm/Group Description	LR-pRBCs derived from Mirasol-treated WB	LR-pRBCs derived from untreated WB
Measure Participants	24	24
Mean (Standard Deviation) [% of volume]	0.103 (0.0338)	0.091 (0.0351)

37. Secondary Outcome

Title	In Vitro Results From Leuko-Reduced Packed Red Blood Cells (LR-pRBCs) - Hemolysis (%)
Time Frame	Day 21

Outcome Measure Data

Analysis Population Description

All subjects who signed an IC Form (were enrolled), and had samples available for the requested test

Arm/Group Title	Mirasol Treated	Untreated Control
Arm/Group Description	LR-pRBCs derived from Mirasol-treated WB	LR-pRBCs derived from untreated WB
Measure Participants	24	24
Mean (Standard Deviation) [% of volume]	0.215 (0.1001)	0.150 (0.0606)

Adverse Events

Time Frame	All AEs collected from the first donation through the end of treatment period 2/study end - SAEs reported from time of 1st WB donation to study exit - TEAEs reported from time of LR-pRBC reinfusion on Day 21 to end of each treatment period
Adverse Event Reporting Description	Only Treatment Emergent AEs (TEAE) reported in final results. TEAEs = AEs that occurred following the Day 21 RBC reinfusion (24 total subj). SAE reporting: from 1st WB donation to study end (29 total subj). Per protocol, subjects were assessed for AEs at each study visit by site staff querying them on their general health since the previous visit
Arm/Group Title	Mirasol Treated		Untreated Control
Arm/Group Description	LR-pRBCs derived from Mirasol-treated WB.		LR-pRBCs derived from untreated WB
All Cause Mortality
	Mirasol Treated		Untreated Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Mirasol Treated		Untreated Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/29 (0%)		0/29 (0%)
Other (Not Including Serious) Adverse Events
	Mirasol Treated		Untreated Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/24 (45.8%)		11/24 (45.8%)
Gastrointestinal disorders
Abdominal discomfort	1/24 (4.2%)		1/24 (4.2%)
Nausea	0/24 (0%)		1/24 (4.2%)
General disorders
Vessel puncture site bruise	5/24 (20.8%)		5/24 (20.8%)
Inflammation	1/24 (4.2%)		0/24 (0%)
Infusion site bruising	0/24 (0%)		1/24 (4.2%)
Infections and infestations
Nasopharyngitis	4/24 (16.7%)		5/24 (20.8%)
Sinusitis	1/24 (4.2%)		1/24 (4.2%)
Cystitis	0/24 (0%)		1/24 (4.2%)
Injury, poisoning and procedural complications
Limb injury	1/24 (4.2%)		0/24 (0%)
Muscle strain	0/24 (0%)		1/24 (4.2%)
Investigations
Haematocrit decreased	1/24 (4.2%)		0/24 (0%)
Musculoskeletal and connective tissue disorders
Back pain	1/24 (4.2%)		1/24 (4.2%)
Nervous system disorders
Sinus headache	1/24 (4.2%)		0/24 (0%)
Tension headache	1/24 (4.2%)		1/24 (4.2%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	1/24 (4.2%)		0/24 (0%)
Oropharyngeal pain	0/24 (0%)		1/24 (4.2%)
Skin and subcutaneous tissue disorders
Skin discolouration	1/24 (4.2%)		0/24 (0%)
Vascular disorders
Peripheral coldness	1/24 (4.2%)		0/24 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.