Ascending Dose Study of FrontlineODP™ Spray Dried Plasma

Evaluation for the Safety of FrontlineODP™ in a Multidose Randomized Cohort Study Compared With PF24

This study in healthy volunteers is designed to assess the safety of infusing increasing doses of spray dried plasma (FrontlineODP).

Study Overview

• Status: Enrolling by invitation
• Conditions: Hemorrhage; Coagulopathy
• Intervention / Treatment: Combination product: Autologous Spray Dried Plasma

Detailed Description

This study in healthy volunteers is designed to assess the safety of infusing increasing doses of spray dried plasma (FrontlineODP). Volunteers will have their plasma collected, spray dried, and then rehydrated for infusion. Volunteers will be infused with their own (autologous) rehydrated plasma. Cohort 1 will receive 1 FrontlineODP unit that is rehydrated to approximately 200 mL. Cohort 2 will receive 2 FrontlineODP units of approximately 400 mL. Cohort 3 volunteers will receive 2 separate infusions of 4 units of approximately 800 mL of either FrontlineODP (experimental) or frozen plasma (PF24). Order of receipt of plasma product will be randomized with 14 days between infusion.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Lisa Buckley, MPH; Phone Number: 1707 978-232-8370; Email: lbuckley@veli.co

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45267-0055
      • Hoxworth Blood Center
      • Contact: Neeta Rugg
      • Principal Investigator: Jose Cancelas
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53233
      • Versiti Blood Center of Wisconsin
    • West Bend, Wisconsin, United States, 53095
      • Spaulding Clinical Research LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Males and nonpregnant/nonbreastfeeding females
• For females, a minimum weight of 140 pounds and maximum weight of 220 pounds; for males, a minimum weight of 140 pounds and a maximum weight of 250 pounds
• Subject is 18 to 65 years of age, inclusive
• Subject self-reports that he or she feels well and healthy
• Subject scores ≥35 on the Duke Activity Status Index
• Subject is able to donate a unit of plasma by plasmapheresis based on the AABB Donor History Questionnaire with modifications indicated: subjects with history of travel, which puts them at risk for Creutzfeldt-Jakob Disease or malaria, are eligible to participate
• Subject has completed a vaccination course for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with the final vaccine injection administered at least 2 weeks before enrollment
• Subject has read the educational materials on donating blood and has had his or her questions answered
• Subject is able and willing to provide written informed consent
• Females of childbearing potential should either be surgically sterile (hysterectomy or tubal ligation) or should use a highly effective medically accepted contraceptive regimen. Highly effective methods of birth control are defined as those which result in a low failure rate (ie, less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intrauterine devices, sexual abstinence, condoms with spermicide, or vasectomized partner
• All females must have a negative urine or serum pregnancy test
• Subject understands the English language

Exclusion Criteria:

• Subject has known liver, kidney, cardiovascular, neurologic, gastrointestinal, blood, endocrine/metabolic, autoimmune, or pulmonary disease, or treated or untreated hypertension
• Subject has cancer of any kind, under treatment or resolved
• Subject has known or past coagulopathy conditions
• Subject has any conditions, uses medications, etc. on the AABB medical deferral list
• Subject has a history of asthma (defined as use of a prescribed daily asthma controller medication or required asthma medication in the past 2 weeks)
• Subject has a previous diagnosis of stroke, deep vein thrombosis (DVT), venous or arterial thrombosis, blood clots, or transient ischemic attack
• Subject has a family history of venous or arterial thrombosis before the age of 50 years in first degree relatives (ie, biological parents, full siblings, or children)
• Subject has a D-dimer test result ≥0.5 FEU/mL
• Subject has a recent (within 1 year of Screening) history of an abnormal electrocardiogram of clinical significance as determined by the site PI
• Subject has known HIV or AIDS-related illness or received a positive test result for HIV infection
• Subject has a positive test result for HBV, hepatitis C virus (HCV), or human T-cell lymphotropic virus
• Subject has a history of significant treated or untreated mental health issues
• Subject is currently taking an antibiotic or another medication for an infection
• Subject has received aspirin or other platelet-inhibiting agents within 14 days of study donation and infusion visits. Prior and concomitant medication information will be recorded beginning 30 days before enrollment through the final follow-up visit
• Subject is currently using any medications for anticoagulant therapy
• Subject has used clotting factor concentrates(s) (eg, FVIIa)
• Subject has received blood or blood products within the past 12 months
• Subject has had concurrent headache and fever in the past week
• Subject has systolic blood pressure (current) greater than 140 mm Hg
• Subject has diastolic blood pressure (current) greater than 90 mm Hg
• Subject has an oral temperature greater than 100°F
• Subject has known hematocrit ≤39% for male donors and ≤38% for female donors
• Subject has a positive DAT result
• Subject has received any investigational agent within 1 month before treatment infusion for this study
• Subject is participating in any phase of any other investigational studies while participating in this study
• Subject is unwilling or unable to comply with the requirements of this protocol, including the presence of any condition (physical, mental, or social) that is likely to affect the subject's return for follow-up visits as scheduled
• Subject has other unspecified reasons that, in the opinion of the site PI, make the subject unsuitable for enrollment
• Subject is institutionalized because of legal or regulatory order
• Subject has a positive urine drug screen

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Subjects are to have sufficient plasma withdrawn during a single plasmapheresis collection in the range of 625 - 800 mL, depending on subject's weight and hematocrit, to allow re-infusion with 1 unit (200 mL) of autologous FrontlineODP.	Combination product: Autologous Spray Dried Plasma; Evaluation of the Safety of Ascending Doses of Autologous Spray Dried Plasma in Healthy Volunteers; Other Names: FrontlineODP Unit; Frontline On Demand Plasma Unit
Experimental: Cohort 2; Subjects are to have sufficient plasma withdrawn during a single plasmapheresis collection, in the range of 625 - 800 mL, depending on subject's weight and hematocrit, to allow re-infusion with 2 units (400 mL) of autologous FrontlineODP.	Combination product: Autologous Spray Dried Plasma; Evaluation of the Safety of Ascending Doses of Autologous Spray Dried Plasma in Healthy Volunteers; Other Names: FrontlineODP Unit; Frontline On Demand Plasma Unit
Active Comparator: Cohort 3 Arm 3; Subject plasma is withdrawn during 4 plasmapheresis collections, in the range of 625 - 800 mL per collection, a total of approximately 2500 - 3200 mL, depending on subject's weight and hematocrit, to allow re-infusion with 4 units of autologous FrontlineODP and 4 units of autologous control PF24. Subjects will receive in total 8 units of plasma over the course of 2 infusion visits. Subjects randomized to Arm 3 will receive 4 units of FrontlineODP during the first infusion visit, and following a 14 day washout period, they would receive 4 units of PF24 during a second visit.	Combination product: Autologous Spray Dried Plasma; Evaluation of the Safety of Ascending Doses of Autologous Spray Dried Plasma in Healthy Volunteers; Other Names: FrontlineODP Unit; Frontline On Demand Plasma Unit
Active Comparator: Cohort 3 Arm 4; Subject plasma is withdrawn during 4 plasmapheresis collections, in the range of 625 - 800 mL per collection, a total of approximately 2500 - 3200 mL, depending on subject's weight and hematocrit, to allow re-infusion with 4 units of autologous control PF24 and 4 units of autologous FrontlineODP. Subjects will receive in total 8 units of plasma over the course of 2 infusion visits. Subjects randomized to Arm 4 will receive 4 units of PF24 during the first infusion visit, and following a 14 day washout period, they would receive 4 units of FrontlineODP during the second visit.	Combination product: Autologous Spray Dried Plasma; Evaluation of the Safety of Ascending Doses of Autologous Spray Dried Plasma in Healthy Volunteers; Other Names: FrontlineODP Unit; Frontline On Demand Plasma Unit

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of Treatment-Emergent Adverse Events (TEAEs)	Conclusions about safety will be based on the occurrence of TEAEs in Cohort 1 (1 unit of FrontlineODP, 200 mL) and Cohort 2 (2 units of FrontlineODP, 400 mL).	Start of plasma infusion through 28 day follow up (Day 29).
Occurrence of Treatment-Emergent Adverse Events (TEAEs)	Conclusions about safety will be based on the occurrence of TEAEs in Cohort 3 with infusions of 4 units (800 mL) of FrontlineODP compared to 4 units (800 mL) of PF24.	Start of first plasma infusion through 28 day follow up of the second infusion (Day 43).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in PT	changes between pre-infusion baseline and 4 hours post-infusion values after infusion of 4 units of FrontlineODP compared with infusion of the same dose of PF24.	Start of first plasma infusion through 28-day follow up of second infusion (Day 43).
Changes in INR	changes between pre-infusion baseline and 4 hours post-infusion values after infusion of 4 units of FrontlineODP compared with infusion of the same dose of PF24.	Start of first plasma infusion through 28-day follow up of second infusion (Day 43).
Changes in aPTT	changes between pre-infusion baseline and 4 hours post-infusion values after infusion of 4 units of FrontlineODP compared with infusion of the same dose of PF24.	Start of first plasma infusion through 28-day follow up of second infusion (Day 43).
Changes in Factor I	changes between pre-infusion baseline and 4 hours post-infusion values after infusion of 4 units of FrontlineODP compared with infusion of the same dose of PF24.	Start of first plasma infusion through 28-day follow up of second infusion (Day 43).
Changes in Factor II	changes between pre-infusion baseline and 4 hours post-infusion values after infusion of 4 units of FrontlineODP compared with infusion of the same dose of PF24.	Start of first plasma infusion through 28-day follow up of second infusion (Day 43).
Changes in Factor V	changes between pre-infusion baseline and 4 hours post-infusion values after infusion of 4 units of FrontlineODP compared with infusion of the same dose of PF24.	Start of first plasma infusion through 28-day follow up of second infusion (Day 43).
Changes in Factor VII	changes between pre-infusion baseline and 4 hours post-infusion values after infusion of 4 units of FrontlineODP compared with infusion of the same dose of PF24.	Start of first plasma infusion through 28-day follow up of second infusion (Day 43).
Changes in Factor VIII	changes between pre-infusion baseline and 4 hours post-infusion values after infusion of 4 units of FrontlineODP compared with infusion of the same dose of PF24.	Start of first plasma infusion through 28-day follow up of second infusion (Day 43).
Changes in Factor IX	changes between pre-infusion baseline and 4 hours post-infusion values after infusion of 4 units of FrontlineODP compared with infusion of the same dose of PF24.	Start of first plasma infusion through 28-day follow up of second infusion (Day 43).
Changes in Factor X	changes between pre-infusion baseline and 4 hours post-infusion values after infusion of 4 units of FrontlineODP compared with infusion of the same dose of PF24.	Start of first plasma infusion through 28-day follow up of second infusion (Day 43).
Changes in Factor XI	changes between pre-infusion baseline and 4 hours post-infusion values after infusion of 4 units of FrontlineODP compared with infusion of the same dose of PF24.	Start of first plasma infusion through 28-day follow up of second infusion (Day 43).
Changes in D-dimer	changes between pre-infusion baseline and 4 hours post-infusion values after infusion of 4 units of FrontlineODP compared with infusion of the same dose of PF24.	Start of first plasma infusion through 28-day follow up of second infusion (Day 43).
Changes in von Willebrand Ristocetin Cofactor (vWF:RCo) activity	changes between pre-infusion baseline and 4 hours post-infusion values after infusion of 4 units of FrontlineODP compared with infusion of the same dose of PF24.	Start of first plasma infusion through 28-day follow up of second infusion (Day 43).
Changes in von Willebrand (vWF) antigen	changes between pre-infusion baseline and 4 hours post-infusion values after infusion of 4 units of FrontlineODP compared with infusion of the same dose of PF24.	Start of first plasma infusion through 28-day follow up of second infusion (Day 43).
Changes in protein S	changes between pre-infusion baseline and 4 hours post-infusion values after infusion of 4 units of FrontlineODP compared with infusion of the same dose of PF24.	Start of first plasma infusion through 28-day follow up of second infusion (Day 43).
Changes in protein C	changes between pre-infusion baseline and 4 hours post-infusion values after infusion of 4 units of FrontlineODP compared with infusion of the same dose of PF24.	Start of first plasma infusion through 28-day follow up of second infusion (Day 43).

Collaborators and Investigators

• Sponsor: Velico Medical
• Investigators: Study Director: Mark Popovsky, MD, Velico Medical

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2022
• Primary Completion (Estimated): May 15, 2024
• Study Completion (Estimated): May 15, 2024

Study Registration Dates

• First Submitted: October 28, 2022
• First Submitted That Met QC Criteria: November 28, 2022
• First Posted (Actual): November 29, 2022

Study Record Updates

• Last Update Posted (Actual): April 26, 2024
• Last Update Submitted That Met QC Criteria: April 25, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: plasmapheresis; dried plasma; coagulation function
• Additional Relevant MeSH Terms: Pathologic Processes; Hemorrhage
• Other Study ID Numbers: IDE 27346

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