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Leukoreduced, Trima Accel® apheresis platelets stored in 100% plasma, pathogen reduced with the Mirasol® Pathogen Reduction Technology (PRT) System

Leukoreduced, apheresis platelets stored in 100% plasma

The final product to be transfused to the subject will be leukoreduced (LR), apheresis (Aph) single-donor platelets (PLTs) at the standard therapeutic dose of 1 unit of Aph PLTs containing ≥ 3.0 × 1.0E11 PLTs. MIR PLTs will be treated with the Mirasol pathogen reduction technology system.

Mirasol platelets (MIR PLTs)

The final product to be transfused to the subject will be LR-Aph single-donor PLTs at the standard therapeutic dose of 1 unit of Aph PLTs containing ≥ 3.0 × 1.0E11 PLTs.

Reference platelets (REF PLTs)

Robert Cortes, MD

Sherrill Slichter, MD

This is a prospective, multi-center, controlled, randomized, non-inferiority study to evaluate the clinical effectiveness of Conventional versus Mirasol-treated apheresis platelets in subjects with hypoproliferative thrombocytopenia who are expected to have platelet count(s) ≤ 10,000/μL requiring ≥ 2 platelet transfusions.

Patients will be randomized 1:1 to Mirasol-treated platelets (test platelets) or to conventional, untreated platelets (control platelets). The blood centers will collect the apheresis donor platelets and supply the test platelets to the hospital sites for transfusion into patients. Hospital sites will order control platelets as per their normal process, from their standard vendor.

The target population for the MIPLATE study are patients with hematologic malignancies with hypoproliferative thrombocytopenia who are expected to have platelet (PLT) count(s) of ≤ 10,000/μL requiring ≥ 2 PLT transfusions.

The primary objective of MIPLATE is to determine if the hemostatic efficacy of Mirasol-treated plasma stored Trima Accel® Aph PLTs are non-inferior to Conventional plasma stored Aph PLTs in subjects with hypoproliferative thrombocytopenia requiring PLT transfusions. The secondary objectives include comparing other efficacy and safety endpoints between the treatment groups.

Subjects with hematologic malignancies with hypoproliferative thrombocytopenia are anticipated to experience a "transfusion episode" where they will require PLT transfusion support until bone marrow recovery. During this period all PLT transfusions required for a study subject will be given according to the subject's treatment allocation for 28 days after the initial PLT transfusion OR until transfusion independence (10 days without PLT transfusion) prior to Day 28.

Additionally, serum samples for HLA antibody testing will be collected on Days 14, 28 and 56.

At a minimum, the initial post-randomization prophylactic PLT transfusion will be initiated for a PLT count ≤ 10,000/µL. Thereafter, indications for PLT transfusions may be PLT count-related prophylaxis, intervention-related prophylaxis, or therapeutic (treatment of active bleeding) as determined by the treating physician(s). The indication(s) for the transfusion(s) will be captured.

Though this is not a blinded study, treatment assignment is obtained through electronic system and should not be shared those performing the primary outcome assessment or assessors of adverse events.

Efficacy of Mirasol-treated Apheresis Platelets in Patients With Hypoproliferative Thrombocytopenia

Clinical Effectiveness of Conventional Versus Mirasol-treated Apheresis Platelets in Patients With Hypoproliferative Thrombocytopenia

UADEs are identified as treatment emergent adverse events reported by the investigator as serious, unanticipated, at least possibly related to study device or at least possibly related to treatment. UADEs were coded using Medical Dictionary for Regulatory Activities (MedDRA) Version 19.1

Number of days of Grade 2 or higher bleeding recorded from treatment start date through 28 days following the first transfusion, until transfusion independence (10 days without PLT transfusion) prior to Day 28, or study termination, whichever occurred first. Subjects who obtained transfusion independence prior to Day 28 were assumed to have zero bleeding events between the date of transfusion independence and Day 28. Observed and simulated data for off-protocol transfusion intervals were included.

The outcome was the development of a new HLA Class I antibodies among subjects negative at baseline within each treatment group. Positivity for Class I HLA antibodies was determined by the 5 SD normalized background ratio cutoffs assay threshold (\>59.2, LABScreen Mixed LSM12, One Lambda).

The number and percentage of subjects with at least 1 day of ≥ Grade 2 bleeding from Day 0 through Day 27 (or until transfusion independence was achieved) by treatment group

The time to first ≥ Grade 2 bleeding was analyzed using a log-rank test comparing survival curves stratified by treatment group.

The number and percentage of subjects with at least 1 day of ≥ Grade 3 bleeding from Day 0 through Day 27 (or until transfusion independence was achieved).

The number and percentage of subjects with PLT refractoriness defined as 2 sequential transfusions, each with corrected count increments (CCIs) \< 5000 measured 1 hour post-transfusion.

The number and percentage of subjects with PLT refractoriness for each treatment group. Subjects were defined as immune PLT refractoriness based on 2 sequential transfusion episodes, each with CCIs \< 5000 measured 1 hour post transfusion, and who also had a positive antibody test within 14 days before or after the onset of PLT refractoriness.

Biomedical Advanced Research and Development Authority

Terumo BCTbio

Treatment Emergent definition: an event that first appears during treatment, which was absent before or which worsened relative to the pre-treatment state. Treatment emergent are those events that occur during or following the first post-randomization PLT transfusion. All TEAEs/TESAEs were followed until resolution, stabilization, or the end of the subject's study participation which occurred first.

Randomized to leukoreduced, Trima Accel® apheresis platelets stored in 100% plasma, pathogen reduced with the Mirasol® Pathogen Reduction Technology (PRT) System

Mirasol platelets (MIR PLTs): The final product to be transfused to the subject will be leukoreduced (LR), apheresis (Aph) single-donor platelets (PLTs) at the standard therapeutic dose of 1 unit of Aph PLTs containing ≥ 3.0 × 1.0E11 PLTs. MIR PLTs will be treated with the Mirasol pathogen reduction technology system.

MIRASOL

Randomized to leukoreduced, apheresis platelets stored in 100% plasma

Reference platelets (REF PLTs): The final product to be transfused to the subject will be LR-Aph single-donor PLTs at the standard therapeutic dose of 1 unit of Aph PLTs containing ≥ 3.0 × 1.0E11 PLTs.

CONTROL

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

American Indian or Alaska Native

Black or African American

Native Hawaiian or Other Pacific Islander

White

Missing

Asian

Other

Race/Ethnicity, Customized

United States

Region of Enrollment

Height (cm)

Weight (kg)

The Dubois formula was used to calculate body surface area (BSA). BSA (m2) = 0.007184 × Height (cm)0.725 × Weight (kg)0.425

Body Surface Area (BSA)

The Safety Analysis Set was used for this analysis. Safety Set (SS) = randomized subjects who received at least 1 PLT transfusion post-randomization, independent of the outcome or successful completions of the procedure. Subjects were analyzed according to the majority treatment received.

The clinical trial was terminated early on the recommendation of the Data Monitoring Committee and in agreement with the Clinical Trial Steering Committee and the Sponsor.

Robert Cortes, Jr. MD

The MIRASOL and CONTROL groups were compared with respect to the number of days of WHO ≥ Grade 2 bleeding. This was carried out by fitting a negative binomial regression model with an offset defined as the natural logarithm (LN) of the number of days that bleeding was assessed in order to account for the fact that subjects had different numbers of bleeding assessment days.

The Modified Intent-to-Treat Analysis Set was used for this analysis. Modified Intent-to-Treat Analysis Set = all randomized subjects who had at least 1 study transfusion according to randomized study group.

Days of ≥ Grade 2 Bleeding

The Modified Intent-to-Treat Analysis Set was used for this analysis. Modified Intent-to-Treat Analysis Set = all randomized subjects who had at least 1 study transfusion according to randomized study group. Subjects who tested positive at the high assay threshold (5 SD normalized background ratio cutoffs \>59.2, LABScreen Mixed LSM12, One Lambda) at Baseline were excluded from this analysis.

Number and Percentage of Subjects With Human Leukocyte Antigen (HLA) Alloimmunization

The null hypothesis was H0: pt/pc \> 1.2 (ie, MIRASOL had more than a 20% higher probability of a patient experiencing at least one WHO ≥ Grade 2 bleed compared to CONTROL).

Number and Percentage of Subjects With ≥ Grade 2 Bleeding

Day 4

Day 8

Day 12

Day 16

Day 20

Day 24

Day 28

The mITT Set was used for this analysis. Subjects that did not experience a ≥ Grade 2 bleed were censored at Day 27 or at date of transfusion independence (10th day without a PLT transfusion prior to last follow-up day or Day 27, whichever occurred earlier), where appropriate. Subjects that did not complete the study or were lost to follow-up were censored on the date of their last study visit in the treatment period.

Number and Percentage of Subjects at the First Timepoint of ≥ Grade 2 Bleeding

Number and Percentage of Subjects With ≥ Grade 3 Bleeding

Number and Percentage of Subjects With PLT Refractoriness

Number and Percentage of Subjects With Immune Platelet Refractoriness

The Safety Set was used for this analysis. Safety Set = randomized subjects who received at least 1 PLT transfusion post-randomization, independent of the outcome or successful completions of the procedure.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Efficacy of Mirasol-treated Apheresis Platelets in Patients With Hypoproliferative Thrombocytopenia	NCT02964325	Hematologic Mal... Hypoproliferati...	Mirasol platele... Reference plate...	-	Terumo BCTbio
Efficacy of Mirasol-treated Apheresis Platelets in Patients With Hypoproliferative Thrombocytopenia	NCT02964325	Hematologic Mal... Hypoproliferati...	Mirasol platele... Reference plate...	-	Terumo BCTbio

Spots Global Cancer Trial Database for reference platelets (ref plts)