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

Tracking Information

• First Submitted Date: October 23, 2017
• First Posted Date: November 6, 2017
• Results First Submitted Date: March 31, 2021
• Results First Posted Date: April 28, 2021
• Last Update Posted Date: April 28, 2021
• Actual Study Start Date: April 23, 2018
• Actual Primary Completion Date: December 19, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 31, 2021)

Normalized Hemoglobin (Hb AUC) Calculated From Normalized Hb Between Successive Transfusions as a Measure of Percent Surviving RBCs [ 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. ]

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.

Original Primary Outcome Measures (submitted: October 27, 2017)

Normalized hemoglobin (Hb AUC) calculated from normalized Hb between successive transfusions as a measure of percent surviving RBCs [ 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 ]

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.

Current Secondary Outcome Measures (submitted: March 31, 2021)

• Hb Increment [ 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 ]
  (post-transfusion Hb - pre-transfusion Hb)/Hb transfused]/RBC volume in subject at pre-transfusion
• 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 ]
  Actual Hb level post-transfusion (15 min)

Original Secondary Outcome Measures (submitted: October 27, 2017)

• Hb increment [ 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 ]
  (post-transfusion Hb - pre-transfusion Hb)/Hb transfused]/RBC volume in subject at pre-transfusion
• 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 ]
  Actual Hb level post-transfusion (15 min)

Current Other Pre-specified Outcome Measures (submitted: March 31, 2021)

• 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 ]
  Proportional decline in post-transfusion Hb level
• RBC Mass Infused [ 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 ]
  volume x Hb/unit
• Incidence of Treatment-emergent Antibody With Confirmed Specificity to RBCs Derived From Mirasol-treated WB [ 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 ]
• Human Leukocyte Antigen (HLA) Alloimmunization Rates [ 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 ]
• Treatment Emergent Adverse Events (TEAEs). [ 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 ]
• Transfusion-related Adverse Events (AEs). [ 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 ]
• Serious Adverse Events (SAEs). [ 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 ]
• Unanticipated Adverse Device Effects (UADEs). [ 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 ]

Original Other Pre-specified Outcome Measures (submitted: October 27, 2017)

• 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 ]
  Proportional decline in post-transfusion Hb level
• RBC mass infused [ 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 ]
  volume x Hb/unit
• Incidence of treatment-emergent antibody with confirmed specificity to RBCs derived from Mirasol-treated WB [ 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 ]
• Human leukocyte antigen (HLA) alloimmunization rates [ 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 ]
• Treatment emergent adverse events (TEAEs). [ 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 ]
• Transfusion-related adverse events (AEs). [ 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 ]
• Serious adverse events (SAEs). [ 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 ]
• Unanticipated adverse device effects (UADEs). [ 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 ]

Descriptive Information

• Brief Title: Efficacy and Safety of RBCs Derived From Mirasol-treated Whole Blood in Patients Requiring Chronic Transfusion (PRAISE)
• Official Title: Evaluate the Efficacy and Safety of RBCs Derived From Mirasol-treated Whole Blood Compared With Conventional RBCs in Patients Requiring Chronic Transfusion Support
• Brief Summary: This is a prospective, multi-center, randomized, crossover trial to evaluate the clinical effectiveness of red blood cells (RBCs) derived from Mirasol-treated whole blood (WB) versus conventional RBCs in transfusion dependent thalassemia patients. Throughout the clinical study, RBC transfusion volume and frequency will be determined by each subject's treating physician.

Detailed Description

Patients will be randomized 1:1 to receive either Mirasol-treated RBCs followed by conventional RBCs, or to receive conventional RBCs followed by Mirasol-treated RBCs. The blood centers will collect the donor RBCs and supply the Mirasol-treated RBCs to the hospital sites for transfusion into patients. Hospital sites will order conventional RBCs as per their normal process, from their standard vendor.

Blood transfusion is the mainstay of care for individuals with thalassemia major. The purpose of transfusion is twofold: to improve the anemia and to suppress the ineffective erythropoiesis. A transfusion episode for these thalassemia patients are the routine transfusions administered on a regular schedule for the life of the patient.

The crossover trial design will consist of 2 treatment periods. Each period will include a 50 day wash-in phase (Day 0 of the wash-in = Day 0 of the treatment period) followed by 2 transfusion episodes. An end of study treatment follow-up visit will occur 2-4 weeks after the last per protocol transfusion, prior to the next standard of care transfusion. A final study visit will occur at least 60 days after the last per protocol transfusion.

The primary objective of the PRAISE study is to determine if percent survival of RBCs derived from Mirasol-treated WB is non-inferior to conventional RBCs when transfused into patients requiring chronic RBC transfusion support. The secondary objectives include comparing other efficacy and safety endpoints between treatment groups.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Transfusion Dependent Thalassemia

Intervention

• Device: Mirasol Red Blood Cells (MIR RBCs)
  Mirasol Red Blood Cells (MIR RBCs) derived from Mirasol-treated WB; WB will be Mirasol treated, centfifuged and leukoreduced and the derived RBCs will be stored before transfusion for up to 21 days and transfused according to the patient's transfusion schedule.
• Device: Reference Red Blood Cells (REF RBCs)
  Reference Red Blood Cells (REF RBCs) will be acquired from routine use inventory and transfused according to the patient's transfusion schedule.

Study Arms

• Experimental: Mirasol Red Blood Cells (MIR RBCs)
  MIR RBCs: RBCs will be derived from WB collected in CPD solution, treated with the Mirasol System for WB, LR, and stored in AS-3 for ≤ 21 days at 1-6°C
  Intervention: Device: Mirasol Red Blood Cells (MIR RBCs)
• Active Comparator: Reference Red Blood Cells (REF RBCs)
  Reference Red Blood Cells (REF RBCs); LR apheresis RBCs or WB-derived RBCs will be per site standard inventory
  Intervention: Device: Reference Red Blood Cells (REF RBCs)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: March 31, 2021): 12
• Original Estimated Enrollment (submitted: October 27, 2017): 97
• Actual Study Completion Date: December 19, 2018
• Actual Primary Completion Date: December 19, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• 1. Transfusion dependent thalassemia patient with mean 2-4 week transfusion intervals for the prior 6 months.

  2. Age ≥ 12 years.

  3. Negative pregnancy test for women of childbearing potential and agreement to practice a medically acceptable contraception regimen throughout the participation in the clinical trial. Not required if female subjects are not of child-bearing potential (ie, prior to menses onset, surgically sterilized, 1-year postmenopausal).

  4. Signed informed consent from the patient, or if the patient is < 18 years of age, signed assent from patient and consent from parent/guardian, according to local Institutional Review Board/Ethics Committee (IRB/EC) requirements.

Exclusion Criteria:

1. Historical RBC transfusion requirement of more than 250 mL/kg/year.
2. Presence of RBC antibodies that make procurement of compatible RBC units not feasible per the treating physician's clinical judgment for reasonable execution of the study.
3. Prior treatment with pathogen-reduced RBCs with subsequent development of known antibodies to the associated RBCs.
4. Planned treatment requirement of frozen RBC products.
5. Treatment requirements for any medication that is known to cause hemolysis.
6. Receiving cardiac medications for heart failure.
7. Patients anticipated to receive massive transfusion, per the treating physician's clinical judgment.
8. Known HIV infection (defined as HIV RNA positive) with changes to antiviral regimen within the 12 months prior to screening.
9. Acute or chronic medical disorder that, in the opinion of the Investigator, would impair the ability of the patient to receive study treatment.
10. Participation in another clinical study, either concurrently or within the previous 28 days, in which the study drug or device may influence study endpoints or patient safety, according to Investigator discretion.
11. Participation in another clinical study within the past 3 months if investigational RBCs or treatment or drugs were received that are likely to have long term effect on RBCs function.
12. Pregnant or breastfeeding.
13. Planned concurrent treatment with other pathogen reduction treated blood products during participation in this study.
14. Patients who received prior treatment with pathogen-reduced RBCs within the past 120 days.
15. Inability to comply with study procedures and/or follow-up.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Israel, Italy, Turkey, United States

Administrative Information

• NCT Number: NCT03329404
• Other Study ID Numbers: CTS-5056
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Terumo BCTbio
• Original Responsible Party: Same as current
• Current Study Sponsor: Terumo BCTbio
• Original Study Sponsor: Same as current

Collaborators

• United States Department of Defense
• Joint Warfighter Medical Research Program
• U.S. Army Medical Research and Development Command

Investigators

• Study Director: Ned Cosgriff, MD; Terumo BCT
• Principal Investigator: Steve Sloan, MD, PhD; Boston Children's Hospital

• PRS Account: Terumo BCTbio
• Verification Date: December 2019