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

Evaluate the Efficacy and Safety of RBCs Derived From Mirasol-treated Whole Blood Compared With Conventional RBCs in Patients Requiring Chronic Transfusion Support

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.

Study Overview

• Status: Terminated
• Conditions: Transfusion Dependent Thalassemia
• Intervention / Treatment: Device: Mirasol Red Blood Cells (MIR RBCs); Device: Reference Red Blood Cells (REF RBCs)

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: Period 1 = Mirasol-treated RBCs followed by conventional (reference) RBCs; Period 2 = Reference RBCs followed by Mirasol-treated RBCs. 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
• Enrollment (Actual): 9
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Israel
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus
  • Jerusalem, Israel, 91120
    • Hadassah Ein Kerem Hospital
• Italy
  • Palermo, Italy, 90146
    • U.O.C. di Ematologia e Malattie Rare del Sangue e degli Organi Ematopoietici V. Cervello Hospital
  • Genoa
    • Genova, Genoa, Italy, 16128
      • Centro della Microcitemia ed Anemie Congenite Ospedale Gallieria
• Turkey
  • Izmir
    • Bornova, Izmir, Turkey, 35040
      • Ege University Children's Hospital
• United States
  • California
    • Oakland, California, United States, 94609
      • UCSF Benioff Children's Hospital Oakland
  • Massachusetts
    • Boston, Massachusetts, United States, 02116
      • Boston Children's Hospital
  • New York
    • New York, New York, United States, 10065
      • Weill-Cornell Medical College
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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	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.
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	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Normalized Hemoglobin (Hb AUC) Calculated From Normalized Hb Between Successive Transfusions as a Measure of Percent Surviving RBCs	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.	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.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Actual Hb Level Post-transfusion (15 Min)	Actual Hb level post-transfusion (15 min)	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
Hb Increment	(post-transfusion Hb - pre-transfusion Hb)/Hb transfused]/RBC volume in subject at pre-transfusion	Endpoint assessments was evaluated at 15 min Post Transfusion, 1 Day Post Transfusion, 7 Day Post Transfusion, and End of Transfusion Episode.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
RBC Mass Infused	volume x Hb/unit	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
Percentage Decline in Post-transfusion Hb Level	Percentage decline in post-transfusion Hb level	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.
Number of Antibody Screening Test With Confirmed Specificity to RBCs Derived From Mirasol-treated WB	Antibody screening was performed in a total of 8 (100%) subjects in the SS at a total of 97 intervals (Pre-Transfusion, 7 Days Post-Transfusion or End of Study Treatment Follow-up Visit).	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
Number of Participants With Human Leukocyte Antigen (HLA) Alloimmunization Post Transfusion	The highest of three different normalized background ratio (NBG) cut-offs was used to quantify positivity for Class I HLA antibodies prior to transfusion as it was used to identify conversion from HLA antibody negative prior to transfusion to positivity after transfusion(s) within the applicable treatment group.	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.

Collaborators and Investigators

• Sponsor: Terumo BCTbio
• Collaborators: United States Department of Defense; U.S. Army Medical Research and Development Command; Joint Warfighter Medical Research Program
• Investigators: Study Director: Ned Cosgriff, MD, Terumo BCT; Principal Investigator: Steve Sloan, MD, PhD, Boston Children's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2018
• Primary Completion (Actual): December 19, 2018
• Study Completion (Actual): December 19, 2018

Study Registration Dates

• First Submitted: October 23, 2017
• First Submitted That Met QC Criteria: October 27, 2017
• First Posted (Actual): November 6, 2017

Study Record Updates

• Last Update Posted (Actual): February 14, 2024
• Last Update Submitted That Met QC Criteria: January 19, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Thalassemia; pathogen reduction therapy
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Thalassemia
• Other Study ID Numbers: CTS-5056

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes