Clinical trial NCT03329404: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Transfusion Dependent Thalassemia
Keywords: Thalassemia
pathogen reduction therapy
Lead sponsor: Terumo BCTbio
Sponsor class: INDUSTRY
Collaborators: name: United States Department of Defense
name: Joint Warfighter Medical Research Program
name: U.S. Army Medical Research and Development Command
First posted: 2017-11-06
Enrollment: 9
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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: 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.

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.

Primary outcomes:
measure: Normalized Hemoglobin (Hb AUC) Calculated From Normalized Hb Between Successive Transfusions as a Measure of Percent Surviving RBCs
timeFrame: 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:
measure: Hb Increment
timeFrame: Endpoint assessments was evaluated at 15 min Post Transfusion, 1 Day Post Transfusion, 7 Day Post Transfusion, and End of Transfusion Episode.
measure: Actual Hb Level Post-transfusion (15 Min)
timeFrame: 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:
measure: Percentage Decline in Post-transfusion Hb Level
timeFrame: 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.
measure: RBC Mass Infused
timeFrame: 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
measure: Number of Antibody Screening Test With Confirmed Specificity to RBCs Derived From Mirasol-treated WB
timeFrame: 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
measure: Number of Participants With Human Leukocyte Antigen (HLA) Alloimmunization Post Transfusion
timeFrame: 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.
Locations:
city: Oakland
country: United States
facility: UCSF Benioff Children's Hospital Oakland
state: California
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: New York
country: United States
facility: Weill-Cornell Medical College
state: New York
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Jerusalem
country: Israel
facility: Hadassah Ein Kerem Hospital
city: Genova
country: Italy
facility: Centro della Microcitemia ed Anemie Congenite Ospedale Gallieria
state: Genoa
city: Palermo
country: Italy
facility: U.O.C. di Ematologia e Malattie Rare del Sangue e degli Organi Ematopoietici V. Cervello Hospital
city: Bornova
country: Turkey
facility: Ege University Children's Hospital
state: Izmir
Study officials:
affiliation: Terumo BCT
name: Ned Cosgriff, MD
role: STUDY_DIRECTOR
affiliation: Boston Children's Hospital
name: Steve Sloan, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: