In Vivo Study to Assess the Recovery and Survival of Radiolabeled Autologous INTERCEPT Apheresis Platelet Components Suspended in 100% Plasma Stored for up to 7 Days

Study Overview
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Brief Summary
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The principle objective of this study is to evaluate the hypothesis that INTERCEPT Platelets in 100% plasma stored for 5 or more days (up to 7 days) after apheresis collection retain sufficient viability for therapeutic transfusion efficacy. The post-infusion recovery and survival of autologous radiolabeled 7 day INTERCEPT platelets (Test) stored in 100% plasma will be measured in comparison to fresh autologous radiolabeled platelets (Control) according to FDA guidance for platelet testing (FDA 1999) in Stage 2 of this study protocol. A secondary objective is to compare the recovery and survival results for Test platelets prepared for radiolabeling using the procedures outlined by the Biomedical Excellence for Safer Transfusion Collaboration (BEST) or a variation of the BEST procedure (referred to as Variant 1) in Stage 1 of this study protocol. Cerus has demonstrated that the Variant 1 method, which does not incorporate an initial soft spin in the presence of ACD A, results in improved in vitro platelet recovery and quality during preparation for radiolabeling compared to the BEST procedure. This comparison will evaluate the hypothesis that preparation methods prior to radiolabeling may influence in vitro quality of the radiolabeled platelets and post-infusion viability outcomes.

Detailed Description
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The study will be performed in two stages. Stage 1 is a randomized, 2-period crossover design. Test platelets stored for 7 days will be radiolabeled based on either the BEST or Variant 1 methods (depending on the period and randomization scheme for the Test platelets) for 12 healthy subjects. The recovery and survival for Test platelets prepared with the BEST and Variant 1 methods will be compared with each other and against the fresh platelet Control. With agreement from the FDA (BQ200481, July 8, 2020), completion of Stage 1 is not required. Stage 2 is a single arm design. Test platelets from 24 healthy subjects, stored for 7 days, will be prepared for radiolabeling following the Variant 1 methodology. The recovery and survival for Test platelets will be compared against the fresh platelet Control. Stage 1 subjects with evaluable Variant 1 method data will contribute to the requirement of the 24 subjects for Stage 2. For both stages, the study population will consist of healthy subjects who meet the FDA, AABB, and site-specific research donor eligibility criteria for apheresis platelet donation. Apheresis platelets will be collected in 100% plasma on the Trima Accel® Automated Blood Collection system. Each study apheresis collection will be processed using the INTERCEPT Blood System for Platelets. Platelet components containing 3.0 to 7.9 x10^11 platelets in 300 to 420 mL of plasma will be processed using the INTERCEPT Dual Storage (DS) set. The INTERCEPT process will begin on either the day of collection (Day 0) or the day following donation (Day 1); illumination must occur within 24 hours after the end of collection. Test platelets components will be stored for up to 7 days, from day of collection, in 100% plasma. During each stage samples for in vitro platelet testing will be collected prior to INTERCEPT treatment (Day 0/1), post INTERCEPT treatment and at the end of storage, Day 7 (see In vitro evaluation of platelets below). At the end of storage, an aliquot of Test platelets will be aseptically removed from each subject's INTERCEPT platelet storage container for preparation of samples for radiolabeling using either the BEST (Stage 1) or Variant 1 (Stages 1 and 2) methodology. The in vitro quality of the Test platelet sample used for radiolabeling will be assessed prior to and following the pre-radiolabeling platelet sample preparations. The indices to be measured in Stage 1 are volume, pH22°C, CD62P, platelet count, red blood cell (RBC) count and white blood cell (WBC) count. Assessments of these indices will enable the determination of platelet processing recovery for each sample preparation method and evaluation of RBC and WBC contamination in samples prior to radiolabeling. In Stage 2 platelet processing recovery during sample preparation will be calculated from volume and platelet count and pH22°C, will be measured in the sample prior to radiolabeling. On the day corresponding to the end of storage for the Test component, healthy subjects will return to the site, and 43 mL of whole blood (WB) will be drawn into a syringe containing 9 mL of Anticoagulant Citrate Dextrose Solution, Formula A (ACD A). The sample will be used to prepare Control platelets following the BEST methodology. Test and Control platelets will be randomly radiolabeled with either 51Cr (approximately10-30μCi) as sodium radiochromate (Na251CrO4) or 111In (approximately 10-30 μCi) as indium oxine, depending upon the randomization assignment and period as applicable. Subjects will be randomized with equal probability to the radiolabeling sequences (111In/51Cr vs. 51Cr/111In) for Test/Control. The isotope labels will be assigned randomly with equal probability that Control and Test platelets will be labeled with each isotope, and the same randomization assignment of isotope labels will be utilized for both apheresis collections for the same subject in Stage 1. After radiolabeling, the autologous Control and Test platelet samples will be simultaneously infused into the subject (approximately 10 30 mL). A negative pregnancy test for females of childbearing potential is required before infusion. Blood samples will be drawn immediately before infusion and for radioactivity measurements at 1 hour ± 15 min and 2 hours ± 15 min post-infusion (Day 0), and 6 more samples will be drawn at 1, 2, 3, 4 (or 5 or 6), 7 or 8, and 11±1 days post-infusion (DPI), at approximately the same time of day as the radiolabeled platelet infusion was administered (±4 hours). The exact time of each sample draw will be recorded. For subjects enrolled in Stage 1, there will be a minimum washout period of four weeks between the two study periods (e.g., four weeks after the last blood sample at 11±1 DPI, in Period 1). Subjects will be monitored for safety (adverse events) from the first apheresis procedure until 24 hours after the last DPI blood sample is drawn.

Official Title
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A Randomized, Multi-center, Open-label, Controlled, In Vivo Study to Assess the Recovery and Survival of Radiolabeled Autologous INTERCEPT Apheresis Platelet Components Suspended in 100% Plasma Stored for up to 7 Days

Conditions
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Healthy

Intervention / Treatment
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* Device: INTERCEPT Treated Platelets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age greater than or equal to 18 years, of either gender. Normal health status (as determined by the Investigator review of medical history and blood donor physical exam). Meet FDA, AABB, and site guidelines for blood donation and apheresis platelet donation. Travel, tattoos/piercings and/or male to male sexual contact deferrals do not apply. Complete blood count (CBC) and serum chemistry values within established reference ranges or within guidelines as above. Pre-donation platelet count of more than 150×10^9 platelets/ L. Negative blood donor screening test panel for HIV, HBV, HCV, HTLV, syphilis, and WNV. Subjects of childbearing potential must agree to use a medically acceptable method of contraception throughout the study. A barrier method of contraception must be included, regardless of other methods. Signed and dated informed consent form. Exclusion Criteria: For participation in Stage 2, received any previous infusion in this study. Clinically significant acute or chronic disease (as determined by the Investigator). Pregnant or nursing females. Subjects of childbearing potential not using effective contraception. Disease states or conditions that preclude apheresis platelet donation per AABB reference standards. Treatment with aspirin or aspirin-containing medications within 7 days of apheresis or treatment with non-steroidal anti-inflammatory drugs (NSAID), anti-platelet agents (or other drugs affecting platelet viability within 3 days of apheresis (e.g., ibuprofen or other NSAIDs). Subject received platelet inhibitors within 14 days of donation (e.g., clopidogrel, ticlopidine, amphetamines (e.g., Adderall, Dexedrine)). Subjects with positive cocaine and/or amphetamine results from urine drug screen. Splenectomized subjects. History of known hypersensitivity to indium or chromium. Has received an investigational drug within the past 28 days

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stage 1<br>The study will be performed in two stages. Stage 1 is a randomized, 2-period crossover design. Test platelets stored for 7 days will be radiolabeled based on either the BEST or Variant 1 methods (depending on the period and randomization scheme for the Test platelets) for 12 healthy subjects. The recovery and survival for Test platelets prepared with the BEST and Variant 1 methods will be compared with each other and against the fresh platelet Control. With agreement from the FDA (BQ200481, July 8, 2020), completion of Stage 1 is not required. | Device: INTERCEPT Treated Platelets<br>* Apheresis platelet components in 100% plasma collected using the Trima separator, prepared with the INTERCEPT Blood System for Platelets (Test Platelets) and stored for 7days at 20-24°C with continuous agitation. Samples from the Test component will be processed with either the BEST or the Variant 1 procedure prior to radiolabeling. The radiolabeled autologous Test and Control platelets (approximately 10-30 mL) will be simultaneously administered intravenously into the subject.<br>|
| Experimental: Stage 2<br>Stage 2 is a single arm design. Test platelets from 24 healthy subjects, stored for 7 days, will be prepared for radiolabeling following the Variant 1 methodology. The recovery and survival for Test platelets will be compared against the fresh platelet Control. Stage 1 subjects with evaluable Variant 1 method data will contribute to the requirement of the 24 subjects for Stage 2. | Device: INTERCEPT Treated Platelets<br>* Apheresis platelet components in 100% plasma collected using the Trima separator, prepared with the INTERCEPT Blood System for Platelets (Test Platelets) and stored for 7days at 20-24°C with continuous agitation. Samples from the Test component will be processed with either the BEST or the Variant 1 procedure prior to radiolabeling. The radiolabeled autologous Test and Control platelets (approximately 10-30 mL) will be simultaneously administered intravenously into the subject.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post Infusion Recovery of Test Platelets at End of Storage (Day 7) | Recovery of Test platelets stored for 7 Days as compared to fresh controls. In vivo recovery was expressed as proportion of infused in days and was estimated using a multiple-hit model. The FDA acceptance criteria for survival is >66% of control with the lower bound of a two-sided 95% CI for the mean treatment difference (Test-0.66*Control) in survival is greater than or equal to zero. | 11 days (+/- 1 day) post infusion of radiolabeled Test platelets stored for 7 days and fresh Control platelets | 
| Post Infusion Survival of Test Platelets at End of Storage | Survival of Test platelets stored for 7 Days as compared to fresh controls. In vivo recovery was expressed as proportion of infused in days and was estimated using a multiple-hit model. The FDA acceptance criteria for survival is >58% of control with the lower bound of a two-sided 95% CI for the mean treatment difference (Test - 0.58 * Control) in survival is greater than or equal to zero. | 11 days (+/- 1 day) post infusion of radiolabeled Test platelets stored for 7 days and fresh Control platelets | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Platelet Dose in Test Component | Percentage of Test components with ≥ 3.0×10^11 platelets | At the end of INTERCEPT treatment on Day 1 or Day 2 | 
| Platelet Yield Retention | Percentage of Test components with ≥80% platelet yield retention | At the end of INTERCEPT treatment on Day 1 or Day 2 | 
| pH 22°C | Percentage of Test components with pH 22°C ≥ 6.2 | At the end of storage on Day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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INTERCEPT, Recovery, Survival, 7 days, Radiolabeled, Autologous