A Phase 2 Study of VLX-1005 Versus Placebo in Suspected Heparin Induced Thrombocytopenia

A Randomized, Double-Blind, Phase 2 Pilot Study of VLX-1005 Versus Placebo in Participants With Suspected Heparin Induced Thrombocytopenia Treated With Background Standard of Care

The purpose of this study is to evaluate the efficacy and safety of VLX-1005, a 12-lipoxygenase (12-LOX) enzyme inhibitor in treating heparin induced thrombocytopenia (HIT). Participants with suspected HIT will receive the usual standard of care, and will be assigned randomly to either VLX-1005 or placebo treatment. The study will measure important outcomes including platelet count, stroke, pulmonary embolus (clot to the lungs) and bleeding.

Study Overview

• Status: Terminated
• Conditions: Heparin Induced Thrombocytopenia; Thrombocytopenia, Immune
• Intervention / Treatment: Drug: VLX-1005; Drug: Placebo

Detailed Description

Over 12 million patients are treated with heparin each year in the United States. Heparin induced thrombocytopenia (HIT) is a recognized complication of heparin therapy and is characterized by the formation of antibodies to heparin and platelet factor 4 (PF4). The scale of the clinical problem is illustrated by cardiopulmonary bypass patients, half of whom develop antibodies to PF4/heparin complexes. In a significant proportion of such seropositive HIT patients, these antibodies will bind to and activate platelets, resulting in a drop in the number of platelets (thrombocytopenia) and activation of the coagulation (clotting) system. Formation of clots in this manner can lead to stroke, heart attacks, damage to internal organs or to limbs, and even death.

The current standard of care with anticoagulants such as argatroban or bivalirudin have not proven effective in reducing poor outcomes in HIT: major morbidity and death rates remain high (> 20%). In addition, these anticoagulants increase the risk of major bleeding (~20%) which can prove to be a fatal complication of such therapy.

VLX-1005 has been developed to address the major unmet clinical need for safer, more effective therapy for HIT. VLX-1005 is a drug that blocks the 12-lipoxygenase (12-LOX) pathway that is believed to be responsible for platelet activation in HIT. In animal models of HIT, VLX-1005 can prevent or treat HIT and halt the development of both thrombocytopenia and abnormal blood clots. The drug has not been associated with increased bleeding in either animals or healthy human volunteers.

The current study will enroll patients suspected of having HIT by clinical measures (4T score) and by laboratory testing (heparin-PF4 immunoassay). Patients will be randomly assigned in a double-blind fashion to either VLX-1005 intravenously or placebo. All patients will receive current guideline mandated therapy for HIT that will include the standard of care anticoagulation: either argatroban or bivalirudin. Patients will be treated for 7 to 14 days until the platelet count has recovered into the normal range. The study will measure important outcomes including platelet count recovery time, stroke, pulmonary embolus, deep vein thrombosis, myocardial infarction, limb and organ injury, and major bleeding.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • MedStar Washington Hospital Center
    • Washington D.C., District of Columbia, United States, 20007
      • Georgetown University
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
    • Philadelphia, Pennsylvania, United States, 19104
      • Universiy of Pennsylvania
  • Virginia
    • Roanoke, Virginia, United States, 24014
      • Carilion Medical Center
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Versiti at Froedtert Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adult participants ≥ 18 years of age.
2. Able to provide informed consent or have informed consent provided on their behalf by a primary caregiver prior to study-related activities being initiated.
3. Recent unfractionated heparin or low-molecular-weight heparin exposure.
4. Qualifying platelet count < 150 X 10^9/L and clinical 4T score of ≥ 4; candidate for argatroban or bivalirudin treatment.

5. Positive PF4-immunoassay (eg, ELISA [≥ 1.0 optical density units], LIA [≥ 1.0 U/mL], CLIA [≥ 1.0 U/mL]).

   -

Exclusion Criteria:

1. Treatment with argatroban or bivalirudin for ≥ 60 hrs prior to randomization.
2. Following discontinuation of heparin, participants cannot be treated with a non-heparin anti-coagulant for ≥ 60 hours.
3. Current renal dialysis.
4. Pregnant or lactating women.
5. Have participated in any other investigational drug trial within 30 days of dosing or 5 half-lives (whichever is longer) in the current study.
6. In the opinion of the investigator, unlikely to comply with key elements of the protocol or otherwise inappropriate for the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VLX-1005; VLX-1005 200 mg given every 12 hours by intravenous infusion over 1 hour.	Drug: VLX-1005; VLX-1005, a 12-LOX enzyme inhibitor; Other Names: 12-LOX enzyme inhibitor
Placebo Comparator: Placebo; Placebo given every 12 hours by intravenous infusion over 1 hour.	Drug: Placebo; Placebo matching VLX-1005; Other Names: Inactive substance similar in appearance to VLX-1005

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to recovery of platelet count to ≥ 150 X 10^9/L in patients with a positive serotonin release assay	Time to platelet count recovery; defined as the time from the first dose of study drug to the time of the first of 2 consecutive platelet count recoveries to ≥ 150 X 10^9/L in patients with positive serotonin release assay (SRA+) confirmed HIT.	Up to 14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite of death, amputation, new thrombosis, stroke, systemic embolism, myocardial infarction, deep vein thrombosis or pulmonary embolism, skin necrosis, limb gangrene, organ ischemia or infarction	Proportion of participants with incidence of the composite of death, amputation, new thrombosis, stroke, systemic embolism, myocardial infarction, deep vein thrombosis or pulmonary embolism, skin necrosis, limb gangrene, organ ischemia or infarction	Up to14 days
Incidence of death, amputation, new thrombosis, stroke, systemic embolism, myocardial infarction, deep vein thrombosis or pulmonary embolism, organ ischemia or infarction	Time from study drug initiation to any incidence of the composite of death, amputation, new thrombosis, stroke, systemic embolism, myocardial infarction, deep vein thrombosis or pulmonary embolism, skin necrosis, limb gangrene, organ ischemia or infarction	Up to14 days
Time from the first dose of study drug to change to oral anti-coagulant treatment	Time from initiation of therapy to switching to oral treatment	Up to14 days
Time from study drug initiation to each element of the composite as a separate endpoint: death, amputation, new thrombosis, stroke, systemic embolism, myocardial infarction, deep vein thrombosis or pulmonary embolism, organ ischemia or infarction	Measurement of important clinical outcomes by time to event	Up to14 days
Proportion of participants with any element of the composite as a separate endpoint: death, amputation, new thrombosis, stroke, systemic embolism, myocardial infarction, deep vein thrombosis or pulmonary embolism, organ ischemia or infarction	Measurement of proportion of participants with important clinical outcomes	Up to14 days
Time from study drug initiation to occurrence of any incidence of International Society on Thrombosis and Haemostasis (ISTH) major bleeding	Incidence of major bleeding by time to event	Up to14 days
Proportion of participants with incidence of major bleeding as defined by ISTH criteria	Measurement of proportion of participants who develop major bleeding	Up to14 days

Collaborators and Investigators

• Sponsor: Veralox Therapeutics
• Investigators: Study Chair: John Alexander, MD, Duke Clinical Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2023
• Primary Completion (Actual): November 17, 2025
• Study Completion (Actual): November 17, 2025

Study Registration Dates

• First Submitted: March 14, 2023
• First Submitted That Met QC Criteria: March 14, 2023
• First Posted (Actual): March 27, 2023

Study Record Updates

• Last Update Posted (Estimated): November 25, 2025
• Last Update Submitted That Met QC Criteria: November 19, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Platelets; Heparin; Thrombocytopenia
• Additional Relevant MeSH Terms: Cytopenia; Pathologic Processes; Autoimmune Diseases; Immune System Diseases; Hemorrhage; Skin Manifestations; Hematologic Diseases; Blood Coagulation Disorders; Hemorrhagic Disorders; Blood Platelet Disorders; Thrombotic Microangiopathies; Purpura, Thrombocytopenic; Purpura; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Hemic and Lymphatic Diseases; Thrombocytopenia; Purpura, Thrombocytopenic, Idiopathic; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors
• Other Study ID Numbers: VLX-1005-003

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