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

Primary Purpose

Transfusion Dependent Thalassemia

Status

Terminated

Phase

Not Applicable

Locations

International

Study Type

Interventional

Intervention

Mirasol Red Blood Cells (MIR RBCs)

Reference Red Blood Cells (REF RBCs)

About this trial

This is an interventional treatment trial for Transfusion Dependent Thalassemia focused on measuring Thalassemia, pathogen reduction therapy

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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:

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.

Sites / Locations

UCSF Benioff Children's Hospital Oakland
Boston Children's Hospital
Weill-Cornell Medical College
The Children's Hospital of Philadelphia
Rambam Health Care Campus
Hadassah Ein Kerem Hospital
Centro della Microcitemia ed Anemie Congenite Ospedale Gallieria
U.O.C. di Ematologia e Malattie Rare del Sangue e degli Organi Ematopoietici V. Cervello Hospital
Ege University Children's Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Mirasol Red Blood Cells (MIR RBCs)

Reference Red Blood Cells (REF RBCs)

Arm Description

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

Reference Red Blood Cells (REF RBCs); LR apheresis RBCs or WB-derived RBCs will be per site standard inventory

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Hb Increment

(post-transfusion Hb - pre-transfusion Hb)/Hb transfused]/RBC volume in subject at pre-transfusion

Actual Hb Level Post-transfusion (15 Min)

Actual Hb level post-transfusion (15 min)

Full Information

NCT ID

NCT03329404

First Posted

October 23, 2017

Last Updated

March 31, 2021

Sponsor

Terumo BCTbio

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT03329404

Brief Title

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

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2019

Overall Recruitment Status

Terminated

Why Stopped

Study suspended due to blood supply challenges. Subsequently approved by FDA to reopen but will not do so because of changing clinical need.

Study Start Date

April 23, 2018 (Actual)

Primary Completion Date

December 19, 2018 (Actual)

Study Completion Date

December 19, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Terumo BCTbio

Collaborators

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

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Yes

Device Product Not Approved or Cleared by U.S. FDA

Yes

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Transfusion Dependent Thalassemia

Keywords

Thalassemia, pathogen reduction therapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

12 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Mirasol Red Blood Cells (MIR RBCs)

Arm Type

Experimental

Arm Description

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

Arm Title

Reference Red Blood Cells (REF RBCs)

Arm Type

Active Comparator

Arm Description

Reference Red Blood Cells (REF RBCs); LR apheresis RBCs or WB-derived RBCs will be per site standard inventory

Intervention Type

Device

Intervention Name(s)

Mirasol Red Blood Cells (MIR RBCs)

Intervention Description

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.

Intervention Type

Device

Intervention Name(s)

Reference Red Blood Cells (REF RBCs)

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Description

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.

Secondary Outcome Measure Information:

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

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

Other Pre-specified Outcome Measures:

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

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

Title

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

Title

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

Title

Treatment Emergent Adverse Events (TEAEs).

Time Frame

Title

Transfusion-related Adverse Events (AEs).

Time Frame

Title

Serious Adverse Events (SAEs).

Time Frame

Title

Unanticipated Adverse Device Effects (UADEs).

Time Frame

10. Eligibility

Sex

All

Minimum Age & Unit of Time

12 Years

Accepts Healthy Volunteers

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: 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ned Cosgriff, MD

Organizational Affiliation

Terumo BCT

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

Steve Sloan, MD, PhD

Organizational Affiliation

Boston Children's Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

UCSF Benioff Children's Hospital Oakland

City

Oakland

State/Province

California

ZIP/Postal Code

94609

Country

United States

Facility Name

Boston Children's Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02116

Country

United States

Facility Name

Weill-Cornell Medical College

City

New York

State/Province

New York

ZIP/Postal Code

10065

Country

United States

Facility Name

The Children's Hospital of Philadelphia

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

Facility Name

Rambam Health Care Campus

City

Haifa

ZIP/Postal Code

3109601

Country

Israel

Facility Name

Hadassah Ein Kerem Hospital

City

Jerusalem

ZIP/Postal Code

91120

Country

Israel

Facility Name

Centro della Microcitemia ed Anemie Congenite Ospedale Gallieria

City

Genova

State/Province

Genoa

ZIP/Postal Code

16128

Country

Italy

Facility Name

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

City

Palermo

ZIP/Postal Code

90146

Country

Italy

Facility Name

Ege University Children's Hospital

City

Bornova

State/Province

Izmir

ZIP/Postal Code

35040

Country

Turkey

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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