Thrombosomes® in Bleeding Thrombocytopenic Patients Study

Study Overview
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Brief Summary
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This prospective, multicenter, randomized, open-label, Phase 2, parallel, dose ranging, multidose trial will enroll patients into 3 Thrombosomes dose groups and 1 control liquid stored platelets (LSP) group in order to evaluate, in a dose-escalation manner, the safety, and impact on bleeding, and the preliminary effect on coagulation measures of increasing doses of allogeneic Thrombosomes in comparison to standard of care, LSP.

Official Title
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A Prospective, Multicenter, Randomized, Open-Label Phase 2, Parallel, Dose Ranging Multidose Study of Thrombosomes® vs Liquid Stored Platelets (LSP) in Bleeding Thrombocytopenic Patients

Conditions
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Thrombocytopenia, Hematologic Malignancy, Bone Marrow Aplasia, Myeloproliferative Disorders, Myelodysplastic Syndromes, Platelet Refractoriness

Intervention / Treatment
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* Biological: Thrombosomes
* Biological: Liquid Stored Platelets (LSP)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults (≥18 years) with TCP as defined by BOTH (a) and (b): a platlet count of ≤ 70,000 platelets/μL blood ANY ONE OR MORE of (1-3): confirmed diagnosis of hematologic malignancy, myeloproliferative disorder, myelodysplastic syndrome, or aplasia undergoing chemotherapy, immunotherapy, radiation therapy or hematopoietic stem cell transplantation refractory to platelet transfusion defined as two 1-hour CCI of <5,000 on consecutive transfusions of LSP or as defined by local site policy (Sacher, 2003) WHO Bleeding Score of 2 or 3 Able to provide informed consent directly or through legally authorized representative, and comply with treatment and monitoring Negative pregnancy test for women of childbearing potential Exclusion Criteria: Any disorder or condition related to any venous thrombosis, embolism, or ischemia within the past 3 months Any disorder or condition related to arterial thrombosis including: ischemia, stroke, MI, or stent placement, within past 6 months Any valve replacement and/or repair of left atrial appendance occlusion device Sinusoidal obstruction syndrom (veno-occlusive disease) or cytopkine release syndrome associated with CAR-T cell therapy Refusal to accept blood products Liver enzyme blood levels greater than 3× the upper limit of normal (ULN) Blood creatinine level greater than 3× ULN Received platelet inhibitor drugs, cyclooxygenase-2 (COX-2) inhibitors, or nonsteroidal anti-inflammatory drugs within 5 days prior to infusion Currently (at the time of randomization) receiving anticoagulant therapy or antiplatelet therapy. Low dose prophylaxis for line clots is not excluded. Receipt of any pro-coagulant agents (e.g., DDAVP, recombinant Factor VIIa or prothrombin complex concentrates (PCC)) other than Tranexamic Acid (TXA) or Epsilon Aminocaproic Acid (EACA, Amicar), within 48 hours of first infusion, or with known hypercoagulable state WHO Bleeding Score of 2 solely due to lumbar puncture, retinal bleeding or GI bleeding or WHO Bleeding Score of 3 solely due to lumbar puncture Receiving L-asparaginase as part of a current cycle of treatment Known inherited or acquired bleeding disorder including, but not limited to: acquired storage pool deficiency or paraproteinemia with platelet inhibition Known inherited or acquired prothrombotic disorders, including antiphospholipid syndrome (Those with lupus anticoagulant or positive antiphospholipid serology without thrombosis are NOT excluded.) Anuria On dialysis Receipt of an investigational drug within 1 month before first infusion, other than for treatment of their underlying disease Females pregnant or nursing or unwilling to use contraception during and for 30 days after taking the study product (females). Evidence of effective birth control may be used, at the discretion of the physician Acute or chronic medical disorder that, in the opinion of the Investigator, would impair the ability of the patient to receive or respond to study treatment Prior participation in this study with successful infusion of the investigational or control product Currently enrolled in other trials not related to their primary disease process or involving platelet transfusions, platelet growth factors, or other pro-coagulant agents

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Dose Ranging Multidose
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Thrombosomes Low Dose<br> | Biological: Thrombosomes<br>* Human platelet derived lyophilized hemostatic<br>|
| Experimental: Thrombosomes Medium Dose<br> | Biological: Thrombosomes<br>* Human platelet derived lyophilized hemostatic<br>|
| Experimental: Thrombosomes High Dose<br> | Biological: Thrombosomes<br>* Human platelet derived lyophilized hemostatic<br>|
| Active Comparator: Liquid Stored Platelets (Control)<br> | Biological: Liquid Stored Platelets (LSP)<br>* Leukocyte reduced apheresis platelets or whole blood derived pooled platelet concentrate equivalent (4-6 units)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Efficacy Endpoint | Cessation or decrease in bleeding at primary bleeding site, based upon the most severe bleeding location at Day 1 baseline taken with in 12 hours prior to infusion, as evidenced by ordinal change in WHO (World Health Organization) Bleeding Score evaluated at 24 hours post initial infusion. | Evaluated at 24 hours post initial infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Efficacy Endpoint assessed by Number of days alive and without WHO (World Health Organization) Grade 2a or greater bleeding | Number of days alive and without WHO (World Health Organization) Grade 2 or greater bleeding through initial 7 days after first Thrombosomes or LSP Infusion | 7 days after first Thrombosomes or LSP infusion | 
| Secondary Efficacy Endpoint assessed by 30 day mortality | 30-day mortality post first infusion of Thrombosomes or post first infusion of LSP as control | 30 days post first infusion (+/- 2 days) | 
| Secondary Efficacy Endpoint assessed by cessation or decrease in bleeding, as evidenced by ordinal change in WHO (World Health Organization) Bleeding Score | Cessation or decrease in primary bleeding site, as evidenced by ordinal change in WHO (World Health Organization) Bleeding Score at 24, 48, 72 hours, Day 4, Day 5, Day 6 and Day 7 after first infusion of Thrombosomes or LSP infusion as control. | 24, 48, 72 hours, Day 4, Day 5, Day 6 and Day 7 post first infusion | 
| Secondary Efficacy Endpoint assessed by cessation or decrease in bleeding, as evidenced by ordinal change in WHO (World Health Organization) Bleeding Score | Cessation or decrease in each additional bleeding site (other than primary bleeding site), as evidenced by ordinal change in WHO (World Health Organization) Bleeding Score at 24, 48, 72 hours, Day 4, Day 5, Day 6 and Day 7 after first infusion of Thrombosomes or LSP infusion as control. | 24, 48, 72 hours, Day 4, Day 5, Day 6 and Day 7 post first infusion | 
| Secondary Efficacy Endpoint assessed for Number, timing, type and reason for administration of all blood products | Number, timing, type and reason for administration of all blood products including platelets and Thrombosomes during the initial 7 days after first Thrombosomes or LSP infusion | 7 days after first Thrombosomes or LSP infusion | 
| Secondary Efficacy Endpoint assessed by platelet count | Platelet count measured at 24, 48, 72 hours and Day 7 of first infusion of Thrombosomes or LSP. Also evaluate at Day 4-6 if patient is hospitalized at that time. | 24, 48, 72 hours and Day 7 post first infusion | 
| Secondary Efficacy Endpoint assessed by measures of hematology | Measures of hematology including: Prothrombin Fragment 1+2; thrombin generation assay (TGA); Thrombopoietin; activated Protein C, tissue plasminogen activator (TPA), and plasminogen activator inhibitor (PAI) per schedule of assessments | From baseline through last study visit (up to 30 days (+/- 2 days)) | 
| Secondary Efficacy Endpoint assessed by measures of coagulation | Measures of coagulation including: prothrombin time (PT); international normalized ratio (INR); fibrinogen; D-dimer; activated partial thromboplastin time (aPTT); and thromboelastography (TEG) or rotational thromboelastometry (ROTEM) per schedule of assessments | From baseline through last study visit (up to 30 days (+/- 2 days)) | 
| Secondary Efficacy Endpoint assessed by changes in markers of endothelial cell injury/repair | Changes in markers of endothelial cell injury/repair from preinfusion baseline through 72 hours after first infusion, including: Syndecan-1, hyaluronan, thrombomodulin, vascular endothelial growth factor (VEGF), interleukin 6, sVE cadherin per schedule of assessments. | From baseline through last study visit (up to 30 days (+/- 2 days)) |