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

NCT03329404 | Terminated Results DMC FDA Device

• 1 other identifier: CTS-5056
• Study Type: interventional
• Target: 9
• Locations: 4 countries
• Sites: 9

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.

Conditions

Transfusion Dependent Thalassemia

Keywords

Thalassemia; pathogen reduction therapy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Hb Increment

  Endpoint assessments was evaluated at 15 min Post Transfusion, 1 Day Post Transfusion, 7 Day Post Transfusion, and End of Transfusion Episode.

• 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

Other Outcomes (4)

• 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.

• RBC Mass Infused

  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

  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

Study Arms (2)

Mirasol Red Blood Cells (MIR RBCs)

EXPERIMENTAL

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)

Reference Red Blood Cells (REF RBCs)

ACTIVE COMPARATOR

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)

Interventions

Mirasol Red Blood Cells (MIR RBCs) DEVICE

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.

Mirasol Red Blood Cells (MIR RBCs)

Reference Red Blood Cells (REF RBCs) DEVICE

Reference Red Blood Cells (REF RBCs) will be acquired from routine use inventory and transfused according to the patient's transfusion schedule.

Reference Red Blood Cells (REF RBCs)

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Transfusion dependent thalassemia patient with mean 2-4 week transfusion intervals for the prior 6 months.
• \. Age ≥ 12 years.
• \. 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).
• \. 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.

You may not qualify if:

• Historical RBC transfusion requirement of more than 250 mL/kg/year.
• 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.
• Prior treatment with pathogen-reduced RBCs with subsequent development of known antibodies to the associated RBCs.
• Planned treatment requirement of frozen RBC products.
• Treatment requirements for any medication that is known to cause hemolysis.
• Receiving cardiac medications for heart failure.
• Patients anticipated to receive massive transfusion, per the treating physician's clinical judgment.
• Known HIV infection (defined as HIV RNA positive) with changes to antiviral regimen within the 12 months prior to screening.
• Acute or chronic medical disorder that, in the opinion of the Investigator, would impair the ability of the patient to receive study treatment.
• 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.
• 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.
• Pregnant or breastfeeding.
• Planned concurrent treatment with other pathogen reduction treated blood products during participation in this study.
• Patients who received prior treatment with pathogen-reduced RBCs within the past 120 days.
• Inability to comply with study procedures and/or follow-up.

Sponsors & Collaborators

• Terumo BCTbio: lead
• United States Department of Defense: collaborator
• Joint Warfighter Medical Research Program: collaborator
• U.S. Army Medical Research and Development Command: collaborator

Study Sites (9)

UCSF Benioff Children's Hospital Oakland

Oakland, California, 94609, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02116, United States

Location

Weill-Cornell Medical College

New York, New York, 10065, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Rambam Health Care Campus

Haifa, 3109601, Israel

Location

Hadassah Ein Kerem Hospital

Jerusalem, 91120, Israel

Location

Centro della Microcitemia ed Anemie Congenite Ospedale Gallieria

Genova, Genoa, 16128, Italy

Location

U.O.C. di Ematologia e Malattie Rare del Sangue e degli Organi Ematopoietici V. Cervello Hospital

Palermo, 90146, Italy

Location

Ege University Children's Hospital

Bornova, İzmir, 35040, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Thalassemia

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

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. Due to the limited dataset we were not able to make any meaningful inferences and as such the data should be viewed with caution.

Results Point of Contact

• Title: Robert Cortes, Jr. MD
• Organization: Terumo Blood and Cell Technologies

Robert.Cortes@terumobct.com

+1.303.231.4353

Study Officials

• Ned Cosgriff, MD

  Terumo BCT

  STUDY DIRECTOR

• Steve Sloan, MD, PhD

  Boston Children's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2017
• First Posted: November 6, 2017
• Study Start: April 12, 2018
• Primary Completion: December 19, 2018
• Study Completion: December 19, 2018
• Last Updated: February 14, 2024
• Results First Posted: April 28, 2021

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

IL (2); US (4); TU (1); IT (2)