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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Device: INTERCEPT Treated Platelets

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45221
      • Hoxworth Blood Center
  • Washington
    • Seattle, Washington, United States, 98102
      • Bloodworks Northwest Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stage 1; 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; 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.
Experimental: Stage 2; 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; 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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of the Stored Test (INTERCEPT) Platelet Components: Component Volume	Component volume was summarized descriptively for Stage 1 and Stage 2 Test components	At the end of storage on Day 7
Assessment of the Stored Test (INTERCEPT) Platelet Components: Platelet Count	Platelet count was summarized descriptively for Stage 1 and Stage 2 Test components	At the end of storage on Day 7
Assessment of the Stored Test (INTERCEPT) Platelet Components: Platelet Dose	Platelet dose was summarized descriptively for Stage 1 and Stage 2 Test components	At the end of storage on Day 7
Assessment of the Stored Test (INTERCEPT) Platelet Components: MPV	MPV was summarized descriptively for Stage 1 and Stage 2 Test components	At the end of storage on Day 7
Assessment of the Stored Test (INTERCEPT) Platelet Components: pO2	pO2 was summarized descriptively for Stage 1 and Stage 2 Test components	At the end of storage on Day 7
Assessment of the Stored Test (INTERCEPT) Platelet Components: Normalized pO2	pO2 normalized for platelet count was summarized descriptively for Stage 1 and Stage 2 Test components	At the end of storage on Day 7
Assessment of the Stored Test (INTERCEPT) Platelet Components: pCO2	pCO2 was summarized descriptively for Stage 1 and Stage 2 Test components	At the end of storage on Day 7
Assessment of the Stored Test (INTERCEPT) Platelet Components: Normalized pCO2	pCO2 was normalized for platelet count and summarized descriptively for Stage 1 and Stage 2 Test components	At the end of storage on Day 7
Assessment of the Stored Test (INTERCEPT) Platelet Components: HCO3	HCO3 was summarized descriptively for Stage 1 and Stage 2 Test components	At the end of storage on Day 7
Assessment of the Stored Test (INTERCEPT) Platelet Components: Normalized HCO3	HCO3 was normalized for platelet count and was summarized descriptively for Stage 1 and Stage 2 Test components	At the end of storage on Day 7
Assessment of the Stored Test (INTERCEPT) Platelet Components: Supernatant Glucose	Supernatant glucose was summarized descriptively for Stage 1 and Stage 2 Test components	At the end of storage on Day 7
Assessment of the Stored Test (INTERCEPT) Platelet Components: Normalized Supernatant Glucose	Supernatant glucose was normalized for platelet count and summarized descriptively for Stage 1 and Stage 2 Test components	At the end of storage on Day 7
Assessment of the Stored Test (INTERCEPT) Platelet Components: Supernatant Lactate	Supernatant lactate was summarized descriptively for Stage 1 and Stage 2 Test components	At the end of storage on Day 7
Assessment of the Stored Test (INTERCEPT) Platelet Components: Normalized Supernatant Lactate	Supernatant lactate was normalized for platelet count and summarized descriptively for Stage 1 and Stage 2 Test components	At the end of storage on Day 7
Assessment of the Stored Test (INTERCEPT) Platelet Components: Total ATP	Total ATP was summarized descriptively for Stage 1 and Stage 2 Test components	At the end of storage on Day 7
Assessment of the Stored Test (INTERCEPT) Platelet Components: Normalized Total ATP	Total ATP was normalized for platelet count and summarized descriptively for Stage 1 and Stage 2 Test components	At the end of storage on Day 7
Assessment of the Stored Test (INTERCEPT) Platelet Components: Morphology	The morphology score quantifies (via phase-contrast light microscopy) the morphological changes of platelets coincident with the full range of platelet activation profile (Units: Kunicki score; Range is 0 to 400). Higher morphology scores represent healthier platelets. Morphology was summarized descriptively for Stage 1 and Stage 2 Test components.	At the end of storage on Day 7
Assessment of the Stored Test (INTERCEPT) Platelet Components: Extent of Shape Change	The Extent of Shape Change is a measurement of agonist-induced, disc-to-sphere shape change of platelets using an aggregometer. It is a quantitative assessment of the proportion of platelets that have discoid morphology in a platelet suspension. Higher values indicate better platelet quality. An aggregometer instrument is to make this measurement. Extent of Shape Change was summarized descriptively for Stage 1 and Stage 2 Test components.	At the end of storage on Day 7
Assessment of the Stored Test (INTERCEPT) Platelet Components: Hypotonic Shock Response	Hypotonic Shock Response is used as an index of platelet integrity and metabolic homeostasis. An aggregometer instrument was used to measure the ability of platelets to recover their volume after being exposed to a hypotonic environment. Higher values of Hypotonic Shock Response indicate better platelet quality. Hypotonic Shock Response was summarized descriptively for Stage 1 and Stage 2 Test components.	At the end of storage on Day 7
Assessment of the Stored Test (INTERCEPT) Platelet Components: Supernatant Lactate Dehydrogenase (LDH) Activity	Supernatant levels of LDH in PCs represent normal plasma LDH plus LDH released by platelets through cell leakage and injury. Supernatant LDH activity was summarized descriptively for Stage 1 and Stage 2 Test components.	At the end of storage on Day 7
Assessment of the Stored Test (INTERCEPT) Platelet Components: Normalized Supernatant LDH	Supernatant LDH activity was normalized for platelet count and was summarized descriptively for Stage 1 and Stage 2 Test components	At the end of storage on Day 7
Assessment of the Stored Test (INTERCEPT) Platelet Components: Total LDH Activity	Total LDH activity was normalized for platelet count and was summarized descriptively for Stage 1 and Stage 2 Test components	At the end of storage on Day 7
Assessment of the Stored Test (INTERCEPT) Platelet Components: Supernatant LDH Proportion of Total LDH	Supernatant LDH Proportion of Total LDH, ratio of LDH supernatant to the total LDH, was summarized descriptively for Stage 1 and Stage 2 Test components	At the end of storage on Day 7
Assessment of the Stored Test (INTERCEPT) Platelet Components: Baseline Adjusted Lysis	For calculation of baseline adjusted lysis the baseline/input supernatant LDH is subtract from the Day 7 supernatant LDH; the lysis is calculated from from the Day 7 adjusted supernatant LDH and Day 7 total LDH values. Baseline Adjusted Lysis was summarized descriptively for Stage 1 and Stage 2 Test components.	At the end of storage on Day 7
Assessment of the Stored Test (INTERCEPT) Platelet Components: P-selectin (CD62P)	Measurement of P-selectin (CD62P) exposure is often used as an index of platelet activation as it is translocated from the alpha granule to the plasma membrane during platelet secretion. This is a sensitive assay to quantify platelet potential for activation. Higher levels of P-selectin indicate more activation. P-selectin was measured by flow cytometry and was summarized descriptively for Stage 1 and Stage 2 Test components.	At the end of storage on Day 7
In Vitro Evaluation of Processed Platelet Samples Prior to Radiolabeling: Sample Volume From Component	Stage 1 and Stage 2 sample volume from platelet component was summarized descriptively for Test samples processed using both the BEST (Stage 1) and Variant 1 (Stage 1 and Stage 2) procedures.	Day 7
In Vitro Evaluation of Processed Platelet Samples Prior to Radiolabeling: Platelet Count	Stage 1 and Stage 2 platelet count was summarized descriptively for Test samples processed using both the BEST (Stage 1) and Variant 1 (Stage 1 and Stage 2) procedures.	Day 7
In Vitro Evaluation of Processed Platelet Samples Prior to Radiolabeling: Platelet Yield (Physical Recovery)	In vitro physical platelet recovery is expressed as the percentage of platelets that are remaining after preparation of the Test sample for radiolabeling, prior to addition of the radiolabel, compared to the number of platelets that were present prior to sample preparation. This measurement shows the loss of platelets during the sample preparations and also provides a process control parameter to ensure that the platelet sample used for radiolabeling is representative of the platelet population in the entire platelet component. Stage 1 and Stage 2 Platelet Yield (Physical Recovery) was summarized descriptively for Test samples processed using both the BEST (Stage 1) and Variant 1 (Stage 1 and Stage 2) procedures.	Day 7
In Vitro Evaluation of Processed Platelet Samples Prior to Radiolabeling: Percentage of Samples With Physical Recovery ≥ 80%	The percentage of Stage 1 and Stage 2 samples with physical recovery ≥ 80% was summarized for Test samples processed using both the BEST (Stage 1) and Variant 1 (Stage 1 and Stage 2) procedures.	Day 7
In Vitro Evaluation of Processed Platelet Samples Prior to Radiolabeling: pH 22°C	Stage 1 and Stage 2 pH 22°C was summarized descriptively for Test samples processed using both the BEST (Stage 1) and Variant 1 (Stage 1 and Stage 2) procedures.	Day 7
In Vitro Evaluation of Processed Platelet Samples Prior to Radiolabeling: Percentage of Samples With pH 22°C ≥ 6.2	The percentage of Stage 1 and Stage 2 samples with pH 22°C ≥ 6.2 was summarized for Test samples processed using both the BEST (Stage 1) and Variant 1 (Stage 1 and Stage 2) procedures.	Day 7
In Vitro Evaluation of Processed Platelet Samples Prior to Radiolabeling: Red Blood Cell Total Count	The Red Blood Cell Total Count was summarized descriptively for Test samples processed using both the BEST and Variant 1 procedures in Stage 1.	Day 7
In Vitro Evaluation of Processed Platelet Samples Prior to Radiolabeling: White Blood Cell Total Count	The White Blood Cell Total Count was summarized descriptively for Test samples processed using both the BEST and Variant 1 procedures in Stage 1.	Day 7
In Vitro Evaluation of Processed Platelet Samples Prior to Radiolabeling: P-selectin Expression (CD62P)	Measurement of P-selectin (CD62P) exposure is often used as an index of platelet activation as it is translocated from the alpha granule to the plasma membrane during platelet secretion. This is a sensitive assay to quantify platelet potential for activation. Higher levels of P-selectin indicate more activation. Measurement of P-selectin prior to radiolabeling allows assessment of the amount of platelet activation induced by the sample preparation process when compared to the Day 7 P-selectin levels in the platelet component. The P-selectin expression (CD62P) was summarized descriptively for Test samples processed using both the BEST and Variant 1 procedures in Stage 1.	Day 7

Collaborators and Investigators

• Sponsor: Cerus Corporation

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2019
• Primary Completion (Actual): April 16, 2021
• Study Completion (Actual): April 17, 2021

Study Registration Dates

• First Submitted: July 9, 2019
• First Submitted That Met QC Criteria: July 15, 2019
• First Posted (Actual): July 17, 2019

Study Record Updates

• Last Update Posted (Actual): October 27, 2022
• Last Update Submitted That Met QC Criteria: September 28, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Survival; Recovery; Autologous; INTERCEPT; 7 days; Radiolabeled
• Other Study ID Numbers: CLI 00127

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes