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COVID-19 ThromboprophylaXIs Study of Novel FXIa Inhibitor Frunexian (EP-7041) in ICU Patients

Primary Purpose

Thrombopenia, Covid19

Status

Withdrawn

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

EP-7041 Injection

About this trial

This is an interventional treatment trial for Thrombopenia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

SARS-CoV-2 test (by local evaluation) positive
Symptom severity and general risk of decompensation warrants, in the opinion of the treating clinician, admission to/care in an intensive care unit setting
Patient or legally authorized representative (LAR) able and willing to provide written informed consent
No contraindication to receiving anticoagulation
At least one D-dimer value ≥2 times local ULN (within 72 hours of hospital admission)

Exclusion criteria

Patients who meet ANY of the following criteria are not eligible for inclusion:

Moribund patient not expected to survive 24 hours
ICU length of stay > 24 hours prior to initiation of frunexian infusion
Existing venous thromboembolism
Known immune compromise (HIV/AIDS, chemotherapy, chronic corticosteroid therapy, transplant patient, etc.)
Active cancer diagnosis
Pregnant, lactating, or parturient woman
bodyweight <40kg
hemoglobin <8.0 g/L in the last 72 hours
platelet count <50 x 109/L in the last 72 hours
known fibrinogen <1.5 g/L (if testing deemed clinically indicated by the treating physician prior to the initiation of anticoagulation)
known INR >1.8 (if testing deemed clinically indicated by the treating physician prior to the initiation of anticoagulation)
patient already on therapeutic anticoagulation at the time of screening (low or high dose nomogram UFH, LMWH, warfarin, or any regular dose of a direct oral anticoagulant)
patient on dual antiplatelet therapy, when at least one of the agents cannot be stopped safely
history of spontaneous intracranial bleeding; gastrointestinal bleeding requiring hospitalization and/or transfusion within prior 3 months
major surgery within prior 30 days
known bleeding within the last 30 days requiring emergency department presentation or hospitalization
known history of a bleeding disorder of an inherited or active acquired bleeding disorder
recent (<48 hours) or planned spinal or epidural anesthesia or puncture
anticipated transfer to another hospital that is not a study site within 72 hours
enrollment in other trials related to anticoagulation or antiplatelet therapy
use of pneumatic compression devices for thromboprophylaxis
Failure to meet ALL Inclusion Criteria

Sites / Locations

VA Greater Los Angeles Healthcare System

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Active Comparator

Arm Label

Active

Institutional Standard

Arm Description

Frunexian infusion 0.6 mg/kg/hr or 1 mg/kg/hr. 0.6 mg/kg/hr dose will be completed first.

Clinician's choice of prophylaxis strategy

Outcomes

Primary Outcome Measures

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

Identify the appropriate dose of EP-7041 that demonstrates safety as defined by incidence of treatment-emergent adverse events

Secondary Outcome Measures

Full Information

NCT ID

NCT05040776

First Posted

September 7, 2021

Last Updated

October 3, 2023

Sponsor

eXIthera Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT05040776

Brief Title

COVID-19 ThromboprophylaXIs Study of Novel FXIa Inhibitor Frunexian (EP-7041) in ICU Patients

Official Title

Prospective, Open-Label Single Ascending Dose Study of Two Dose Levels of Frunexian (EP-7041), Followed by a Randomized Comparison of One Dose With Institutional Standard Care, for Thromboprophylaxis in Patients Managed in Intensive Care Settings for COVID-19 Syndrome: The COVID-ThromboprophylaXIs Study

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Withdrawn

Why Stopped

Sponsor decision

Study Start Date

October 2023 (Anticipated)

Primary Completion Date

May 2024 (Anticipated)

Study Completion Date

May 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

eXIthera Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This is a multicenter, open-label, single cohort study of patients with confirmed COVID-19 syndrome who based on clinical judgment require care in an intensive care unit, regardless of whether or not mechanical ventilation is in use or is anticipated. Patients should be enrolled on the first day of the ICU stay; withdrawal of prior thromboprophylaxis, if any, will follow specific protocol guidance. Enrolled patients will thereafter be administered intravenous frunexian (EP-7041) until disposition from the hospital (including post-ICU non-critical care management)

Detailed Description

The goal of the COVID-ThromboprophylaXIs Study is to determine the safety and tolerability of two doses of frunexian (EP-7041) for the prevention of thromboembolism in the management of COVID-19 patients, compared to control patients managed with institutional standard care thromboprophylaxis regimens. Dosing of frunexian for the first 15 patients enrolled will be randomized to 0.6 mg/kg/hr IV (n=15) and next 15 patients will be randomized to 1.0 mg/kg/hr IV (n=15) for the duration of the index hospitalization. Enrollment will be paused after treatment of these 30 patients, at which time a dedicated DSMB will evaluate all collected safety data through 7 days post-index hospital discharge. If no adverse safety signal is identified for the 1.0 mg/kg/hr dose, enrollment will be resumed with the study dose of frunexian randomized 2:1 to 1.0 mg/kg/hr or institutional standard care for thromboprophylaxis in ICU patients with COVID-19. If safety concerns are identified for the higher dose and not for the lower dose, then open-label randomized enrollment vs institutional standard of care for thromboprophylaxis will proceed with an frunexian dose of 0.6 mg/kg/hr. The second phase of the study will enroll 60 additional patients, with 40 in the frunexian dosing arm, and 20 in the standard care arm.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Thrombopenia, Covid19

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

Multicenter, Open Label, Single Dose Escalation Study

Masking

None (Open Label)

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Active

Arm Type

Other

Arm Description

Frunexian infusion 0.6 mg/kg/hr or 1 mg/kg/hr. 0.6 mg/kg/hr dose will be completed first.

Arm Title

Institutional Standard

Arm Type

Active Comparator

Arm Description

Clinician's choice of prophylaxis strategy

Intervention Type

Drug

Intervention Name(s)

EP-7041 Injection

Other Intervention Name(s)

EP-7041, Frunexian

Intervention Description

EP-7041 infusion

Primary Outcome Measure Information:

Title

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

Description

Identify the appropriate dose of EP-7041 that demonstrates safety as defined by incidence of treatment-emergent adverse events

Time Frame

30 days after discharge

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: SARS-CoV-2 test (by local evaluation) positive Symptom severity and general risk of decompensation warrants, in the opinion of the treating clinician, admission to/care in an intensive care unit setting Patient or legally authorized representative (LAR) able and willing to provide written informed consent No contraindication to receiving anticoagulation At least one D-dimer value ≥2 times local ULN (within 72 hours of hospital admission) Exclusion criteria Patients who meet ANY of the following criteria are not eligible for inclusion: Moribund patient not expected to survive 24 hours ICU length of stay > 24 hours prior to initiation of frunexian infusion Existing venous thromboembolism Known immune compromise (HIV/AIDS, chemotherapy, chronic corticosteroid therapy, transplant patient, etc.) Active cancer diagnosis Pregnant, lactating, or parturient woman bodyweight <40kg hemoglobin <8.0 g/L in the last 72 hours platelet count <50 x 109/L in the last 72 hours known fibrinogen <1.5 g/L (if testing deemed clinically indicated by the treating physician prior to the initiation of anticoagulation) known INR >1.8 (if testing deemed clinically indicated by the treating physician prior to the initiation of anticoagulation) patient already on therapeutic anticoagulation at the time of screening (low or high dose nomogram UFH, LMWH, warfarin, or any regular dose of a direct oral anticoagulant) patient on dual antiplatelet therapy, when at least one of the agents cannot be stopped safely history of spontaneous intracranial bleeding; gastrointestinal bleeding requiring hospitalization and/or transfusion within prior 3 months major surgery within prior 30 days known bleeding within the last 30 days requiring emergency department presentation or hospitalization known history of a bleeding disorder of an inherited or active acquired bleeding disorder recent (<48 hours) or planned spinal or epidural anesthesia or puncture anticipated transfer to another hospital that is not a study site within 72 hours enrollment in other trials related to anticoagulation or antiplatelet therapy use of pneumatic compression devices for thromboprophylaxis Failure to meet ALL Inclusion Criteria

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Charles V. Pollack, Jr.,, MA, MD

Organizational Affiliation

Department of Emergency Medicine, University of Mississippi School of Medicine

Official's Role

Study Director

Facility Information:

Facility Name

VA Greater Los Angeles Healthcare System

City

Los Angeles

State/Province

California

ZIP/Postal Code

90073

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

COVID-19 ThromboprophylaXIs Study of Novel FXIa Inhibitor Frunexian (EP-7041) in ICU Patients

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