Clinical Trial Assessing Non-Inferiority of Freeze Dried Plasma to Fresh Frozen Plasma in Reversing Warfarin

NCT04794348 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: S-18-04
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to see how well an experimental freeze dried plasma product, known as FDP, works to reverse the anticoagulation effects of a prescription medication called warfarin sodium (warfarin) compared to a licensed and routinely used plasma product known as fresh frozen plasma (FFP). The study hypothesis is that FDP is not inferior to FFP when used for this purpose. Enrolled subjects are required to undergo a minimum of 4 plasmapheresis procedures, generating approximately 2,400 mL. Half will be used as FFP and half will be manufactured into FDP. Each subject will receive a total of 6 autologous units (approximately 1,620 mL) of plasma product over the course of 2 infusion visits (approximately 810 mL per infusion visit) with a 14 day washout period between infusions. Warfarin will be administered to each subject prior to each infusion visit. Subjects will be randomized to a treatment arm at their first warfarin administration visit leading up to the first infusion. This establishes the sequence of the plasma products to be infused across the 2 infusion visits. Those randomized to receive 3 units of FDP (approximately 810 mL) at the first infusion visit will receive the equivalent dose of FFP at their second infusion visit and vice versa for those randomized to receive 3 units of FFP at the first infusion visit. FDP and FFP will be infused intravenously.

Conditions

Anticoagulant Reversal

Outcome Measures

Primary Outcomes (2)

• Relative change in International Normalized Ratio (INR)

  Relative change in INR between pre-infusion baseline and the lowest INR recovery value measured within 6 hours post infusion using equivalent 3-unit doses of FDP compared to FFP

  pre-infusion baseline, 6 hours post infusion

• Occurrence of treatment emergent adverse events (TEAE)

  Conclusions about safety will be based on the occurrence of TEAEs

  Start of first plasma infusion through 14 day follow up visit post second plasma infusion

Secondary Outcomes (12)

• Changes in INR

  pre-infusion baseline, 6 hours post infusion

• Changes in aPTT

  pre-infusion baseline, 6 hours post infusion

• Changes in Factor II (FII)

  pre-infusion baseline, 6 hours post infusion

• Changes in Factor VII (FVII)

  pre-infusion baseline, 6 hours post infusion

• Changes in Factor IX (FIX)

  pre-infusion baseline, 6 hours post infusion

Study Arms (2)

Fresh Frozen Plasma (FFP)

ACTIVE COMPARATOR

Subjects will undergo plasmapheresis to generate approximately 1200 mL of fresh frozen plasma. After completion of warfarin dosing, approximately 810 mL of fresh frozen plasma will be intravenously administered to the subject.

Biological: Fresh Frozen Plasma (FFP)

Freeze Dried Plasma (FDP)

EXPERIMENTAL

Subjects will undergo plasmapheresis to generate approximately 1200 mL, that will be manufactured into freeze dried plasma units. After completion of warfarin dosing, approximately 810 mL of freeze dried plasma will be intravenously administered to the subject.

Biological: Freeze Dried Plasma (FDP)

Interventions

Freeze Dried Plasma (FDP) BIOLOGICAL

Autologous units of freeze dried plasma manufactured from plasma collected from the subject by plasmapheresis

Freeze Dried Plasma (FDP)

Fresh Frozen Plasma (FFP) BIOLOGICAL

Autologous units of fresh frozen plasma collected from the subject by plasmapheresis

Fresh Frozen Plasma (FFP)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be a male or non-pregnant/non-breastfeeding female;
• Males must weigh ≥ 140 and ≤ 250 pounds; females must weigh ≥ 140 and ≤ 220 pounds;
• Be ≥ 18 and ≤ 65 years of age;
• Self-report that he or she feels well and healthy;
• Score ≥ 35 on the Duke Activity Status Index (see Appendix 3);
• Be eligible to make plasmapheresis donations based on the AABB Full-Length Donor History Questionnaire with the exception that subjects with a history of travel that puts them at risk for Creutzfeldt-Jakob Disease, malaria, West Nile virus, or Zika virus are eligible for this trial;
• Males who have sex with men (MSM) and are in monogamous sexual relationships will be allowed to donate and participate in the trial. Other MSM relations will require a 3 month deferral period from the last sexual relation.
• Have read the educational materials about donating plasma and the information provided on diet, alcohol consumption, warfarin use, and restrictions during the trial;
• Be able and willing to provide written informed consent;
• Be available for the duration of the trial (approximately 18 to 28 weeks) and able to come to the treatment clinic for scheduled trial visits;
• Females 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 that result in a lower failure rate (i.e., less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, intrauterine devices, sexual abstinence, condoms with spermicide, or vasectomized partner.
• All females must have a negative pregnancy test prior to enrollment. Post-menopausal females (women over 50 years of age who, in the absence of pregnancy, have a minimum of 2 months without menses) and females who have had a hysterectomy or oophorectomy will not be tested; and
• Understand the English language.

You may not qualify if:

• Known liver, kidney, cardiovascular, neurologic, gastrointestinal, blood, endocrine/metabolic, autoimmune or pulmonary disease, or untreated hypertension;
• Cancer of any kind (except basal cell) under treatment or resolved;
• Known or past coagulopathy conditions;
• Any medical conditions or medications on the American Association of Blood Banks (AABB) medical deferral list;
• Past history of asthma (defined as use of a prescribed daily asthma controller medication or required asthma medication in the past 2 weeks);
• Past diagnosis of stroke, deep vein thrombosis (DVT), venous or arterial thrombosis, blood clots, or transient ischemic attack;
• Family history of venous or arterial thrombosis before the age of 50 in first-degree relatives (i.e., biological parents, full siblings, and/or children);
• D-dimer result \> 2.0 FEU/mL;
• Subjects known to be deficient in protein C or protein S, or found to be deficient as assessed by the investigator based on the screening testing;
• History of diagnosed pathological arrhythmia;
• Current smoker (defined as having smoked any form of inhalant within the past 6 months);
• Subjects who are HIV negative and at high risk for contracting HIV who are currently using pre-exposure prophylaxis (PrEP®) as a prevention method;
• Known HIV or acquired immunodeficiency syndrome-related illness or received a positive test result for HIV infection;
• Positive test for hepatitis B virus, hepatitis C virus, human T-cell lymphotropic virus (HTLV), West Nile virus, Zika virus, or syphilis;
• History of significant treated or untreated mental health issues;

Sponsors & Collaborators

• Teleflex: lead
• Westat: collaborator
• United States Army Medical Materiel Development Activity: collaborator

Study Sites (1)

Hoxworth Blood Center

Cincinnati, Ohio, 45219, United States

Location

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2021
• First Posted: March 12, 2021
• Study Start: May 1, 2021
• Primary Completion: March 1, 2022
• Study Completion: March 1, 2022
• Last Updated: April 2, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)