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

• Sponsor: Terumo BCTbio (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02964325
• Collaborator: Biomedical Advanced Research and Development Authority (U.S. Fed)
• Enrollment: 422
• Locations: 10
• Arms: 2
• Actual Duration (Months): 37.7
• Patients Per Site: 42.2
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Hematologic Malignancies; Hypoproliferative Thrombocytopenia	Device: Mirasol platelets (MIR PLTs); Device: Reference platelets (REF PLTs)	N/A

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 422 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Investigator, Outcomes Assessor)
• Masking Description: 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.
• Primary Purpose: Supportive Care
• Official Title: Clinical Effectiveness of Conventional Versus Mirasol-treated Apheresis Platelets in Patients With Hypoproliferative Thrombocytopenia
• Actual Study Start Date: May 5, 2017
• Actual Primary Completion Date: Jun 25, 2020
• Actual Study Completion Date: Jun 25, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Mirasol platelets (MIR PLTs) Leukoreduced, Trima Accel® apheresis platelets stored in 100% plasma, pathogen reduced with the Mirasol® Pathogen Reduction Technology (PRT) System	Device: 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.
Active Comparator: Reference platelets (REF PLTs) Leukoreduced, apheresis platelets stored in 100% plasma	Device: 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.

Outcome Measures

Primary Outcome Measures

1. Days of ≥ Grade 2 Bleeding [From the first post-randomization platelet transfusion through 28 days following the first transfusion.]

   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.

Secondary Outcome Measures

1. Number and Percentage of Subjects With Human Leukocyte Antigen (HLA) Alloimmunization [HLA antibodies were measured at Baseline and Days 14, 28, and 56.]

   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).

2. Number and Percentage of Subjects With ≥ Grade 2 Bleeding [From the first post-randomization platelet transfusion through 28 days following the first transfusion.]

   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

3. Number and Percentage of Subjects at the First Timepoint of ≥ Grade 2 Bleeding [From the first post-randomization platelet transfusion through 28 days following the first transfusion.]

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

4. Number and Percentage of Subjects With ≥ Grade 3 Bleeding [From the first post-randomization platelet transfusion through 28 days following the first transfusion.]

   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).

5. Number and Percentage of Subjects With PLT Refractoriness [From the first post-randomization platelet transfusion through 28 days following the first transfusion.]

   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.

6. Number and Percentage of Subjects With Immune Platelet Refractoriness [Initial post-randomization platelet transfusion through high Class I HLA development.]

   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.

Other Outcome Measures

1. Number and Percentage of Subjects With Unanticipated Adverse Device Effects (UADEs) [From initial post-randomization PLT transfusion through 72 hours following the last per protocol PLT transfusion.]

   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

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Weight > 10 kg (22 lbs)

2. Subject has a hematologic malignancy with hypoproliferative thrombocytopenia and is expected to have PLT count(s) ≤ 10,000/µL requiring ≥ 2 PLT transfusions

3. Laboratory results within 5 days prior to anticipated initiation of the first post randomization PLT transfusion:

4. Prothrombin time (PT) and/or international normalized ratio (INR) ≤ 1.3 × the upper limit of normal (ULN)

5. Activated partial thromboplastin time (aPTT) ≤ 1.3 × ULN

6. Fibrinogen ≥ 100 mg/dL

7. Women of childbearing potential must have a negative pregnancy test and agree to practice a medically acceptable contraception regimen for the study duration. Women who are postmenopausal for at least 1 year (> 12 months since last menses) or are surgically sterilized do not require this test

8. IC from the subject or assent from the subject and consent from a parent or guardian, if the subject is < 18 years of age

Exclusion Criteria:

1. Treatment with pathogen-reduced blood products within previous 6 months

2. Subject has been previously enrolled in this study and received at least 1 per protocol PLT transfusion

3. a.) Subject is receiving therapeutic doses of antiplatelet agents, antifibrinolytics, and/or PLT specific growth factors within 10 days prior to randomization or b.) Subject is receiving therapeutic doses of anticoagulant, pro-coagulant or antithrombotic agents within 10 days prior to randomization. Subjects can be included if receiving the following: prophylactic dosing of anticoagulants (heparin, any low molecular weight heparin, enoxaparin, or fondaparinux), anticoagulants/thrombolytic agents used to maintain or re-establish the patency of catheters (heparin flushes or tissue-plasminogen activase [TPA], therapeutic doses of anticoagulants with a half-life of < 24 hours if it will be discontinued at least 24 hours prior to the first study transfusion, single periprocedural doses of anticoagulants with a half-life of < 24 hours or low dose aspirin (81 mg per day)

4. Subject has ≥ grade 2 bleeding at the time of randomization

5. Planned administration of bedside LR PLT transfusion(s)

6. Presently with or a history of acute promyelocytic leukemia (APML), idiopathic thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura (TTP), or hemolytic uremic syndrome (HUS)

7. HLA and/or HPA-alloimmunization and/or platelet refractory as determined by the investigator

8. Hypersplenism as evidenced by splenomegaly based on investigator assessment at baseline

9. History or diagnosis of a disease affecting hemostasis

10. Currently taking, or participating in a clinical study involving PLT substitutes, PLT growth factors, or pharmacologic agents intended to enhance (i.e, antifibrinolytic agents) or decrease PLT hemostatic function

11. Acute or chronic medical disorder that, in the opinion of the investigator, would impair the ability of the subject to receive protocol treatment

12. Subject is pregnant or lactating

13. Inability of the subject to comply with study procedures and/or follow-up

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's National Medical Center	Washington	District of Columbia	United States	20010
2	University of Florida Health Shands Hospital	Gainesville	Florida	United States	32608
3	Emory University/Children's Hospital of Atlanta	Atlanta	Georgia	United States	30322
4	University of Iowa	Iowa City	Iowa	United States	52242
5	John Hopkins University School of Medicine/Johns Hopkins Kimmel Cancer Center	Baltimore	Maryland	United States	21231
6	Boston Children's Hospital	Boston	Massachusetts	United States	02115
7	Washington University in St. Louis	Saint Louis	Missouri	United States	63110
8	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198
9	Robert Wood Johnson Medical School/RWJ University Hospital	New Brunswick	New Jersey	United States	08903
10	University of Washington Medical Center	Seattle	Washington	United States	98109

Sponsors and Collaborators

• Terumo BCTbio
• Biomedical Advanced Research and Development Authority

Investigators

• Study Director: Robert Cortes, MD, Terumo BCT
• Principal Investigator: Sherrill Slichter, MD, Bloodworks Northwest

Study Documents (Full-Text)

• Study Protocol - Jan 30, 2019
• Statistical Analysis Plan - Sep 2, 2020

More Information

Publications

None provided.

• Responsible Party: Terumo BCTbio
• ClinicalTrials.gov Identifier: NCT02964325
• Other Study ID Numbers: CTS-5030
• First Posted: Nov 16, 2016
• Last Update Posted: Aug 19, 2021
• Last Verified: Jul 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Keywords provided by Terumo BCTbio: hypoproliferative thrombocytopenia; hematologic malignancies; thrombocytopenia; platelet therapy; apheresis; pathogen reduction therapy
• Additional relevant MeSH terms: Neoplasms; Hematologic Neoplasms; Thrombocytopenia

Study Results

Participant Flow

Recruitment Details

Recruitment occurred at 11 hospital sites within the US. Enrollment occurred between 05 MAY 2017 and 07 APR 2020.

Pre-assignment Detail

Full Analysis Set (FAS) - all randomized subjects. Safety Set (SS) - randomized subjects who received at least 1 PLT transfusion post-randomization, independent of the outcome or successful completions of the procedure. Modified Intent-to-Treat (mITT) - all randomized subjects who had at least 1 study transfusion according to randomized study group. 422 subjects consented, 92 screen failed, 330 FAS, 28 received no transfusion, 302 SS, 5 received no transfusion per assigned group, 297 mITT.

Arm/Group Title	MIRASOL	CONTROL
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	164	166
Full Analysis Set	164	166
Modified Intent-to-Treat	145	152
Safety Set	141	161
COMPLETED	143	143
NOT COMPLETED	21	23

Baseline Characteristics

Arm/Group Title	MIRASOL	CONTROL	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	141	161	302
Age (Count of Participants)
<=18 years	6 4.3%	10 6.2%	16 5.3%
Between 18 and 65 years	94 66.7%	100 62.1%	194 64.2%
>=65 years	41 29.1%	51 31.7%	92 30.5%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.8 (16.32)	54.1 (18.24)	54.4 (17.34)
Sex: Female, Male (Count of Participants)
Female	53 37.6%	56 34.8%	109 36.1%
Male	88 62.4%	105 65.2%	193 63.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	8 5.7%	8 5%	16 5.3%
Not Hispanic or Latino	130 92.2%	147 91.3%	277 91.7%
Unknown or Not Reported	3 2.1%	6 3.7%	9 3%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	1 0.7%	0 0%	1 0.3%
Black or African American	16 11.3%	10 6.2%	26 8.6%
Native Hawaiian or Other Pacific Islander	0 0%	1 0.6%	1 0.3%
White	120 85.1%	137 85.1%	257 85.1%
Missing	0 0%	1 0.6%	1 0.3%
Asian	2 1.4%	10 6.2%	12 4%
Other	2 1.4%	2 1.2%	4 1.3%
Region of Enrollment (Count of Participants)
United States	141 100%	161 100%	302 100%
Height (cm) (centimeters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeters]	170.29 (15.039)	167.88 (18.472)	169.01 (16.972)
Weight (kg) (kilograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms]	86.96 (23.876)	84.95 (25.400)	85.89 (24.680)
Body Surface Area (BSA) (square meters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [square meters]	1.975 (0.3157)	1.934 (0.3613)	1.953 (0.3408)

Outcome Measures

1. Primary Outcome

Title	Days of ≥ Grade 2 Bleeding
Description	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.
Time Frame	From the first post-randomization platelet transfusion through 28 days following the first transfusion.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	MIRASOL	CONTROL
Arm/Group Description	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.	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.
Measure Participants	145	152
Mean (Standard Deviation) [Days]	1.7 (4.05)	0.6 (1.51)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MIRASOL, CONTROL
	Comments	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.
	Type of Statistical Test	Non-Inferiority
	Comments	An NI analysis was carried out to assess the primary efficacy endpoint with the null hypothesis being the MIRASOL group is inferior to the CONTROL group and the alternative hypothesis being the MIRASOL group is non-inferior to the CONTROL group. In this study, the NI margin was 1.6.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative Rate
	Estimated Value	2.79
	Confidence Interval	(2-Sided) 95%; 1.67 to 4.67
	Parameter Dispersion	Type: Value:
	Estimation Comments	The MIRASOL group represents the numerator and the CONTROL group represents the denominator for the relative rate. For days during off-protocol intervals, bleeding data were simulated using an estimate of the individual-specific bleeding rate.

2. Secondary Outcome

Title	Number and Percentage of Subjects With Human Leukocyte Antigen (HLA) Alloimmunization
Description	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).
Time Frame	HLA antibodies were measured at Baseline and Days 14, 28, and 56.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	MIRASOL	CONTROL
Arm/Group Description	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.	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.
Measure Participants	136	141
Count of Participants [Participants]	4 2.8%	2 1.2%

3. Secondary Outcome

Title	Number and Percentage of Subjects With ≥ Grade 2 Bleeding
Description	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
Time Frame	From the first post-randomization platelet transfusion through 28 days following the first transfusion.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	MIRASOL	CONTROL
Arm/Group Description	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.	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.
Measure Participants	145	152
Count of Participants [Participants]	58 41.1%	46 28.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MIRASOL, CONTROL
	Comments	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).
	Type of Statistical Test	Non-Inferiority
	Comments	A non-inferiority margin of 1.2 was used to evaluated this endpoint.
Statistical Test of Hypothesis	p-Value	0.7274
	Comments
	Method	Wald Non-inferiority Test
	Comments
Method of Estimation	Estimation Parameter	Relative Risk
	Estimated Value	1.32
	Confidence Interval	(2-Sided) 95%; 0.97 to 1.81
	Parameter Dispersion	Type: Value:
	Estimation Comments	The MIRASOL group represents the numerator and the CONTROL group represents the denominator for the relative risk.

4. Secondary Outcome

Title	Number and Percentage of Subjects at the First Timepoint of ≥ Grade 2 Bleeding
Description	The time to first ≥ Grade 2 bleeding was analyzed using a log-rank test comparing survival curves stratified by treatment group.
Time Frame	From the first post-randomization platelet transfusion through 28 days following the first transfusion.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	MIRASOL	CONTROL
Arm/Group Description	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.	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.
Measure Participants	145	152
Day 4	115 81.6%	128 79.5%
Day 8	92 65.2%	110 68.3%
Day 12	72 51.1%	85 52.8%
Day 16	33 23.4%	48 29.8%
Day 20	11 7.8%	27 16.8%
Day 24	5 3.5%	13 8.1%
Day 28	4 2.8%	11 6.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MIRASOL, CONTROL
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.07
	Comments
	Method	Log-rank test
	Comments

5. Secondary Outcome

Title	Number and Percentage of Subjects With ≥ Grade 3 Bleeding
Description	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).
Time Frame	From the first post-randomization platelet transfusion through 28 days following the first transfusion.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	MIRASOL	CONTROL
Arm/Group Description	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.	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.
Measure Participants	145	152
Count of Participants [Participants]	6 4.3%	2 1.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MIRASOL, CONTROL
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1649
	Comments
	Method	Fisher Exact
	Comments

6. Secondary Outcome

Title	Number and Percentage of Subjects With PLT Refractoriness
Description	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.
Time Frame	From the first post-randomization platelet transfusion through 28 days following the first transfusion.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	MIRASOL	CONTROL
Arm/Group Description	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.	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.
Measure Participants	145	152
Count of Participants [Participants]	41 29.1%	20 12.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MIRASOL, CONTROL
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0015
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	2.15
	Confidence Interval	(2-Sided) 95%; 1.32 to 3.49
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Number and Percentage of Subjects With Immune Platelet Refractoriness
Description	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.
Time Frame	Initial post-randomization platelet transfusion through high Class I HLA development.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	MIRASOL	CONTROL
Arm/Group Description	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.	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.
Measure Participants	136	141
Count of Participants [Participants]	1 0.7%	1 0.6%

8. Other Pre-specified Outcome

Title	Number and Percentage of Subjects With Unanticipated Adverse Device Effects (UADEs)
Description	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
Time Frame	From initial post-randomization PLT transfusion through 72 hours following the last per protocol PLT transfusion.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	MIRASOL	CONTROL
Arm/Group Description	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.	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.
Measure Participants	141	161
Blood and Lymphatic System Disorders/ Febrile Neutropenia	1 0.7%	0 0%
No UADEs	140 99.3%	161 100%

Adverse Events

Time Frame	Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) that occurred from initial post randomization platelet transfusion through seventy-two (72) hours following the transfusion end time of the last on-protocol PLT transfusion were reported. Deaths that occurred (including deaths due to bleeding) thirty days (30) following the transfusion end time of the last on-protocol PLT transfusion were reported.
Adverse Event Reporting Description	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.
Arm/Group Title	MIRASOL		CONTROL
Arm/Group Description	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.		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.
All Cause Mortality
	MIRASOL		CONTROL
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/141 (0.7%)		3/161 (1.9%)
Serious Adverse Events
	MIRASOL		CONTROL
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/141 (15.6%)		33/161 (20.5%)
Blood and lymphatic system disorders
Febrile neutropenia	4/141 (2.8%)	4	11/161 (6.8%)	12
Cardiac disorders
Cardiomyopathy	0/141 (0%)	0	1/161 (0.6%)	1
Right ventricular dysfunction	0/141 (0%)	0	1/161 (0.6%)	1
Sinus tachycardia	1/141 (0.7%)	1	0/161 (0%)	0
Tachycardia	1/141 (0.7%)	1	0/161 (0%)	0
Gastrointestinal disorders
Abdominal pain	1/141 (0.7%)	1	0/161 (0%)	0
Diaphragmatic hernia	1/141 (0.7%)	1	0/161 (0%)	0
Vomiting	0/141 (0%)	0	1/161 (0.6%)	1
General disorders
Pyrexia	0/141 (0%)	0	4/161 (2.5%)	4
Hepatobiliary disorders
Acute hepatic failure	0/141 (0%)	0	1/161 (0.6%)	1
Bile duct stone	0/141 (0%)	0	1/161 (0.6%)	1
Venoocclusive liver disease	0/141 (0%)	0	1/161 (0.6%)	1
Immune system disorders
Cytokine release syndrome	1/141 (0.7%)	1	0/161 (0%)	0
Engraftment syndrome	0/141 (0%)	0	1/161 (0.6%)	1
Graft versus host disease in gastrointestinal tract	0/141 (0%)	0	1/161 (0.6%)	1
Infections and infestations
Septic Shock	2/141 (1.4%)	2	2/161 (1.2%)	3
Streptococcal bacteremia	2/141 (1.4%)	2	2/161 (1.2%)	2
Bacteraemia	3/141 (2.1%)	3	0/161 (0%)	0
Staphylococcal bacteraemia	1/141 (0.7%)	1	1/161 (0.6%)	1
Stomatococcal infection	2/141 (1.4%)	2	0/161 (0%)	0
Bronchopulmonary aspergillosis	1/141 (0.7%)	1	0/161 (0%)	0
Candida infection	1/141 (0.7%)	1	0/161 (0%)	0
Cellulitis	0/141 (0%)	0	1/161 (0.6%)	1
Clostridium difficile infection	0/141 (0%)	0	1/161 (0.6%)	1
Cystitis viral	1/141 (0.7%)	1	0/161 (0%)	0
Device related infection	0/141 (0%)	0	1/161 (0.6%)	1
Diverticulitis	0/141 (0%)	0	1/161 (0.6%)	1
Enterococcal bacteraemia	1/141 (0.7%)	1	0/161 (0%)	0
Enterococcal infection	0/141 (0%)	0	1/161 (0.6%)	1
Human herpesvirus 6 infection	1/141 (0.7%)	1	0/161 (0%)	0
Pneumonia	0/141 (0%)	0	1/161 (0.6%)	1
Pseudomonal bacteraemia	1/141 (0.7%)	1	0/161 (0%)	0
Septic arthritis staphylococcal	0/141 (0%)	0	1/161 (0.6%)	1
Escherichia bacteraemia	1/141 (0.7%)	1	1/161 (0.6%)	1
Injury, poisoning and procedural complications
Allergic transfusion reaction	0/141 (0%)	0	1/161 (0.6%)	1
Delayed engraftment	0/141 (0%)	0	1/161 (0.6%)	1
Febrile nonhaemolytic transfusion reaction	1/141 (0.7%)	1	0/161 (0%)	0
Procedural hypotension	0/141 (0%)	0	1/161 (0.6%)	1
Transfusion-associated dyspnoea	0/141 (0%)	0	1/161 (0.6%)	1
Transfusion-related circulatory overload	0/141 (0%)	0	1/161 (0.6%)	1
Transplant failure	0/141 (0%)	0	1/161 (0.6%)	1
Investigations
Blood culture positive	1/141 (0.7%)	1	0/161 (0%)	0
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain	0/141 (0%)	0	1/161 (0.6%)	1
Nervous system disorders
Cerebrovascular accident	1/141 (0.7%)	1	0/161 (0%)	0
Encephalopathy	0/141 (0%)	0	1/161 (0.6%)	1
Syncope	0/141 (0%)	0	1/161 (0.6%)	1
Psychiatric disorders
Mental status changes	2/141 (1.4%)	2	0/161 (0%)	0
Renal and urinary disorders
Acute kidney injury	1/141 (0.7%)	1	1/161 (0.6%)	1
Renal impairment	0/141 (0%)	0	1/161 (0.6%)	1
Urinary retention	1/141 (0.7%)	1	0/161 (0%)	0
Respiratory, thoracic and mediastinal disorders
Respiratory failure	0/141 (0%)	0	2/161 (1.2%)	3
Dyspnoea	1/141 (0.7%)	1	0/161 (0%)	0
Pneumonia aspiration	0/141 (0%)	0	1/161 (0.6%)	1
Vascular disorders
Hypotension	3/141 (2.1%)	3	2/161 (1.2%)	2
Deep vein thrombosis	1/141 (0.7%)	1	1/161 (0.6%)	1
Embolism	1/141 (0.7%)	1	0/161 (0%)	0
Other (Not Including Serious) Adverse Events
	MIRASOL		CONTROL
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	97/141 (68.8%)		100/161 (62.1%)
Blood and lymphatic system disorders
Febrile neutropenia	24/141 (17%)	27	17/161 (10.6%)	17
Anaemia	12/141 (8.5%)	12	11/161 (6.8%)	11
Gastrointestinal disorders
Diarrhoea	21/141 (14.9%)	21	35/161 (21.7%)	35
Vomiting	19/141 (13.5%)	19	14/161 (8.7%)	14
Nausea	12/141 (8.5%)	12	8/161 (5%)	8
Abdominal pain	6/141 (4.3%)	6	11/161 (6.8%)	11
Stomatitis	11/141 (7.8%)	11	6/161 (3.7%)	6
General disorders
Pyrexia	19/141 (13.5%)	20	16/161 (9.9%)	17
Mucosal inflammation	15/141 (10.6%)	15	19/161 (11.8%)	19
Oedema peripheral	15/141 (10.6%)	18	13/161 (8.1%)	14
Fatigue	13/141 (9.2%)	13	9/161 (5.6%)	9
Injury, poisoning and procedural complications
Febrile nonhaemolytic transfusion reaction	7/141 (5%)	13	8/161 (5%)	9
Metabolism and nutrition disorders
Hypokalaemia	14/141 (9.9%)	15	20/161 (12.4%)	20
Decreased appetite	8/141 (5.7%)	8	8/161 (5%)	8
Hypomagnesaemia	8/141 (5.7%)	8	8/161 (5%)	8
Nervous system disorders
Headache	9/141 (6.4%)	9	11/161 (6.8%)	12
Dizziness	7/141 (5%)	8	9/161 (5.6%)	11
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	11/141 (7.8%)	11	10/161 (6.2%)	10

Limitations/Caveats

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.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.