Efficacy and Safety of RBCs Derived From Mirasol-treated Whole Blood in Patients Requiring Chronic Transfusion (PRAISE) (PRAISE)

• ClinicalTrials.gov Identifier: NCT03329404
• Recruitment Status: Terminated
• First Posted: November 6, 2017
• Results First Posted: April 28, 2021
• Last Update Posted: April 28, 2021
• Sponsor: Terumo BCTbio
• Collaborators: United States Department of Defense; Joint Warfighter Medical Research Program; U.S. Army Medical Research and Development Command
• Information provided by (Responsible Party): Terumo BCTbio

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Transfusion Dependent Thalassemia
• Interventions: Device: Mirasol Red Blood Cells (MIR RBCs); Device: Reference Red Blood Cells (REF RBCs)
• Enrollment: 12

Participant Flow

Recruitment Details

A subject was considered enrolled upon signing the informed consent. The first subject was enrolled on 12 April 2018 and the last subject was enrolled on 26 October 2018.

Pre-assignment Details

This was a crossover study, all 9 randomized subjects were to receive both Mirasol and Reference RBCs in either period 1 or 2. 4 subjects were randomized to the MIR/REF RBC treatment sequence and 5 subjects were randomized to the REF/MIR RBC sequence. 4 subjects completed period 1, no subjects completed period 2 due to study suspension. Because no subjects completed the study, the primary endpoint was not evaluated and results are summarized by treatment type rather than treatment sequence.

Arm/Group Title	Mirasol Red Blood Cells (MIR RBCs) Followed by Reference RBCs (REF RBCs)	Reference Red Blood Cells (REF RBCs) Followed by Mirasol RBCs (MIR RBCs)
Arm/Group Description	MIR RBCs: RBCs were derived from whole blood (WB) collected in citrate phosphate dextrose (CPD) solution, treated with the Mirasol System for WB, Leukoreduced (LR), and stored in Additive Solution Formula 3 (AS-3) for ≤ 21 days at 1 - 6°C. REF RBCs: LR apheresis RBCs or WB-derived RBCs were per site standard inventory.	REF RBCs: Leukoreduced (LR) apheresis RBCs or whole blood (WB)-derived RBCs were per site standard inventory. MIR RBCs: RBCs were derived from WB collected in citrate phosphate dextrose (CPD) solution, treated with the Mirasol System for WB, LR, and stored in Additive Solution Formula 3 (AS-3) for ≤ 21 days at 1 - 6°C.
Period Title: Overall Study
Started	4	5
Completed [1]	3	1
Not Completed	1	4
Reason Not Completed
The study was suspended.	1	4
[1] 4 subjects were randomized to the MIR/REF RBC treatment sequence, 3 of the 4 subjects completed the first arm of the study and 1 subject did not complete the first arm of the study. 5 subjects were randomized to the REF/MIR RBC treatment sequence, 1 of the 5 subjects completed the first arm of the study and 4 subjects did not complete the first arm of the study. In summary- no subjects completed the entire study and 4 subjects completed one arm of the study.

Baseline Characteristics

Arm/Group Title		Mirasol Red Blood Cells (MIR RBCs)/Reference Red Blood Cells (REF RBCs) Treatment Sequence	Reference Red Blood Cells (REF RBCs)/Mirasol Red Blood Cells (MIR RBCs) Treatment Sequence	Total
Arm/Group Description		MIR RBCs: RBCs were derived from whole blood (WB) collected in citrate phosphate dextrose (CPD) solution, treated with the Mirasol System for WB, Leukoreduced (LR), and stored in Additive Solution Formula 3 (AS-3) for ≤ 21 days at 1 - 6°C. REF RBCs: LR apheresis RBCs or WB-derived RBCs were per site standard inventory.	REF RBCs: Leukoreduced (LR) apheresis RBCs or whole blood (WB)-derived RBCs were per site standard inventory. MIR RBCs: RBCs were derived from WB collected in citrate phosphate dextrose (CPD) solution, treated with the Mirasol System for WB, LR, and stored in Additive Solution Formula 3 (AS-3) for ≤ 21 days at 1 - 6°C.	Total of all reporting groups
Overall Number of Baseline Participants		4	5	9
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	4 participants	5 participants	9 participants
	<=18 years	1 25.0%	1 20.0%	2 22.2%
	Between 18 and 65 years	3 75.0%	4 80.0%	7 77.8%
	>=65 years	0 0.0%	0 0.0%	0 0.0%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	4 participants	5 participants	9 participants
	Female	2 50.0%	1 20.0%	3 33.3%
	Male	2 50.0%	4 80.0%	6 66.7%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	4 participants	5 participants	9 participants
	Hispanic or Latino	0 0.0%	0 0.0%	0 0.0%
	Not Hispanic or Latino	3 75.0%	5 100.0%	8 88.9%
	Unknown or Not Reported	1 25.0%	0 0.0%	1 11.1%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	4 participants	5 participants	9 participants
		4	5	9

Outcome Measures

1. Primary Outcome

Title	Normalized Hemoglobin (Hb AUC) Calculated From Normalized Hb Between Successive Transfusions as a Measure of Percent Surviving RBCs
Description	The Hb AUC is calculated using the trapezoidal method on normalized Hb. The normalization is accomplished by dividing all posttransfusion Hb values by the 15-minute posttransfusion Hb level. The ratio is expressed as a percentage. A natural log-transform of the observed normalized Hb AUC will be utilized.
Time Frame	Crossover design with 2 treatment periods. Each period included a 50-day wash-in followed by 2 transfusion episodes for primary endpoint assessment. Expected participation was approximately 7-10 months, depending on the subject's transfusion schedule.

Outcome Measure Data

Analysis Population Description

The full Statistical Analysis Plan was not executed for this study because the study was stopped prematurely. 97 subjects were planned to be enrolled however only 12 subjects enrolled and 9 were randomized. Of the 9 randomized, no subjects completed the study due to early termination of the study. The primary outcome measure was not analyzed due to the small sample size and premature termination of the study.

Arm/Group Title	Mirasol Red Blood Cells (MIR RBCs)	Reference Red Blood Cells (REF RBCs)
Arm/Group Description:	MIR RBCs: RBCs were derived from whole blood (WB) collected in citrate phosphate dextrose (CPD) solution, treated with the Mirasol System for WB, Leukoreduced (LR), and stored in Additive Solution Formula 3 (AS-3) for ≤ 21 days at 1 - 6°C. REF RBCs: LR apheresis RBCs or WB-derived RBCs were per site standard inventory.	REF RBCs: Leukoreduced (LR) apheresis RBCs or whole blood (WB)-derived RBCs will be per site standard inventory. MIR RBCs: RBCs will be derived from WB collected in citrate phosphate dextrose (CPD) solution, treated with the Mirasol System for WB, LR, and stored in Additive Solution Formula 3 (AS-3) for ≤ 21 days at 1 - 6°C.
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

2. Secondary Outcome

Title	Hb Increment
Description	(post-transfusion Hb - pre-transfusion Hb)/Hb transfused]/RBC volume in subject at pre-transfusion
Time Frame	An average of 30 weeks consisting of 2 crossover treatment periods with each period including a 50 day wash-in phase followed by 2 transfusion episodes for endpoint assessment

Outcome Measure Data Not Reported

3. Secondary Outcome

Title	Actual Hb Level Post-transfusion (15 Min)
Description	Actual Hb level post-transfusion (15 min)
Time Frame	An average of 30 weeks consisting of 2 crossover treatment periods with each period including a 50 day wash-in phase followed by 2 transfusion episodes for endpoint assessment

Outcome Measure Data Not Reported

4. Other Pre-specified Outcome

Title	Proportional Decline in Post-transfusion Hb Level
Description	Proportional decline in post-transfusion Hb level
Time Frame	An average of 30 weeks consisting of 2 crossover treatment periods with each period including a 50 day wash-in phase followed by 2 transfusion episodes for endpoint assessment

Outcome Measure Data Not Reported

5. Other Pre-specified Outcome

Title	RBC Mass Infused
Description	volume x Hb/unit
Time Frame	An average of 30 weeks consisting of 2 crossover treatment periods with each period including a 50 day wash-in phase followed by 2 transfusion episodes for endpoint assessment

Outcome Measure Data Not Reported

6. Other Pre-specified Outcome

Title	Incidence of Treatment-emergent Antibody With Confirmed Specificity to RBCs Derived From Mirasol-treated WB
Description	[Not Specified]
Time Frame	Up to 40 weeks consisting of 2 crossover treatment periods with each period including a 50 day wash-in phase followed by 2 transfusion episodes for endpoint assessment and a final study visit 60 days after last study transfusion

Outcome Measure Data Not Reported

7. Other Pre-specified Outcome

Title	Human Leukocyte Antigen (HLA) Alloimmunization Rates
Description	[Not Specified]
Time Frame	An average of 15 weeks consisting of the first treatment period including a 50 day wash-in phase followed by 2 transfusion episodes

Outcome Measure Data Not Reported

8. Other Pre-specified Outcome

Title	Treatment Emergent Adverse Events (TEAEs).
Description	[Not Specified]
Time Frame	Up to 40 weeks consisting of 2 crossover treatment periods with each period including a 50 day wash-in phase followed by 2 transfusion episodes for endpoint assessment and a final study visit 60 days after last study transfusion

Outcome Measure Data Not Reported

9. Other Pre-specified Outcome

Title	Transfusion-related Adverse Events (AEs).
Description	[Not Specified]
Time Frame	Up to 40 weeks consisting of 2 crossover treatment periods with each period including a 50 day wash-in phase followed by 2 transfusion episodes for endpoint assessment and a final study visit 60 days after last study transfusion

Outcome Measure Data Not Reported

10. Other Pre-specified Outcome

Title	Serious Adverse Events (SAEs).
Description	[Not Specified]
Time Frame	Up to 40 weeks consisting of 2 crossover treatment periods with each period including a 50 day wash-in phase followed by 2 transfusion episodes for endpoint assessment and a final study visit 60 days after last study transfusion

Outcome Measure Data Not Reported

11. Other Pre-specified Outcome

Title	Unanticipated Adverse Device Effects (UADEs).
Description	[Not Specified]
Time Frame	Up to 40 weeks consisting of 2 crossover treatment periods with each period including a 50 day wash-in phase followed by 2 transfusion episodes for endpoint assessment and a final study visit 60 days after last study transfusion

Outcome Measure Data Not Reported

Adverse Events

Time Frame	8 months
Adverse Event Reporting Description	This was a crossover study, therefore adverse events are reported by treatment received, some subjects received both treatments. Of the 9 randomized subjects, 1 subject did not receive any study transfusions, 4 of the 9 subjects received some MIR RBC transfusions and 8 of the 9 subjects received some REF RBC transfusions.
Arm/Group Title	Mirasol Red Blood Cells (MIR RBCs)		Reference Red Blood Cells (REF RBCs)
Arm/Group Description	MIR RBCs: RBCs were derived from whole blood (WB) collected in citrate phosphate dextrose (CPD) solution, treated with the Mirasol System for WB, leukoreduced, and stored in Additive Solution Formula 3 (AS-3) for ≤ 21 days at 1 - 6°C.		REF RBCs: Leukoreduced apheresis RBCs or whole blood-derived RBCs were per site standard inventory.
All-Cause Mortality
	Mirasol Red Blood Cells (MIR RBCs)		Reference Red Blood Cells (REF RBCs)
	Affected / at Risk (%)		Affected / at Risk (%)
Total	0/4 (0.00%)		0/8 (0.00%)
Serious Adverse Events
	Mirasol Red Blood Cells (MIR RBCs)		Reference Red Blood Cells (REF RBCs)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0.00%)		0/8 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Mirasol Red Blood Cells (MIR RBCs)		Reference Red Blood Cells (REF RBCs)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/4 (25.00%)		4/8 (50.00%)
Blood and lymphatic system disorders
Thrombocytosis † 1	1/4 (25.00%)	1	0/8 (0.00%)	0
Thrombocytopenia † 1	0/4 (0.00%)	0	1/8 (12.50%)	1
Infections and infestations
Viral upper respiratory tract infection † 1	0/4 (0.00%)	0	1/8 (12.50%)	1
Investigations
Aspartate aminotransferase increased † 1	0/4 (0.00%)	0	1/8 (12.50%)	1
Alanine aminotransferase increased † 1	0/4 (0.00%)	0	1/8 (12.50%)	1
Metabolism and nutrition disorders
Hypoglycemia † 1	1/4 (25.00%)	1	0/8 (0.00%)	0
Skin and subcutaneous tissue disorders
Rash † 1	0/4 (0.00%)	0	1/8 (12.50%)	1
1 Term from vocabulary, MedDRA Version 19.0; † Indicates events were collected by systematic assessment

Limitations and Caveats

The primary endpoint was not evaluated due to the early termination of the study and subsequent small sample size with no subjects completing both Period 1 and Period 2 of the study preventing any meaningful results.

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Robert Cortes, Jr. MD
• Organization: Terumo Blood and Cell Technologies
• Phone: +1.303.231.4353
• EMail: Robert.Cortes@terumobct.com

• Responsible Party: Terumo BCTbio
• ClinicalTrials.gov Identifier: NCT03329404
• Other Study ID Numbers: CTS-5056
• First Submitted: October 23, 2017
• First Posted: November 6, 2017
• Results First Submitted: March 31, 2021
• Results First Posted: April 28, 2021
• Last Update Posted: April 28, 2021