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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05785819
Recruitment Status : Recruiting
First Posted : March 27, 2023
Last Update Posted : September 29, 2023
Sponsor:
Information provided by (Responsible Party):
Veralox Therapeutics

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Thrombocytopenia, Immune Heparin Induced Thrombocytopenia Drug: VLX-1005 Drug: Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : September 26, 2023
Estimated Primary Completion Date : December 21, 2024
Estimated Study Completion Date : March 31, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Blood Thinners
Drug Information available for: Heparin

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 Name: 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 Name: Inactive substance similar in appearance to VLX-1005




Primary Outcome Measures :
  1. Time to recovery of platelet count to ≥ 150 X 10^9/L in patients with a positive serotonin release assay [ Time Frame: Up to 14 days ]
    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.


Secondary Outcome Measures :
  1. 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 [ Time Frame: Up to14 days ]
    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

  2. Incidence of death, amputation, new thrombosis, stroke, systemic embolism, myocardial infarction, deep vein thrombosis or pulmonary embolism, organ ischemia or infarction [ Time Frame: Up to14 days ]
    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

  3. Time from the first dose of study drug to change to oral anti-coagulant treatment [ Time Frame: Up to14 days ]
    Time from initiation of therapy to switching to oral treatment

  4. 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 [ Time Frame: Up to14 days ]
    Measurement of important clinical outcomes by time to event

  5. 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 [ Time Frame: Up to14 days ]
    Measurement of proportion of participants with important clinical outcomes

  6. Time from study drug initiation to occurrence of any incidence of International Society on Thrombosis and Haemostasis (ISTH) major bleeding [ Time Frame: Up to14 days ]
    Incidence of major bleeding by time to event

  7. Proportion of participants with incidence of major bleeding as defined by ISTH criteria [ Time Frame: Up to14 days ]
    Measurement of proportion of participants who develop major bleeding



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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. Previous treatment with argatroban or bivalirudin for > 48 hr prior to randomization.
  2. Participants cannot receive other anti-coagulants, such as fondaparinux and danaparoid, or direct oral anti-coagulants, such as rivaroxaban as initial standard of care.
  3. QT interval corrected by the method of Fridericia (QTcF) > 450 msec for males, > 470 msec for females.
  4. History of hepatitis C antibody, hepatitis B surface antigen, or human immunodeficiency virus (HIV) antibody at screening.
  5. Current renal disease with a calculated creatinine clearance less than 30 mL/min.
  6. Participants with a history of substance abuse or dependency or history of recreational IV drug use (by self-declaration).
  7. Participant has a suspected history of alcohol abuse in the 6 months prior to screening.
  8. Participants who are unlikely to comply with the study protocol or, in the opinion of the investigator, would not be a suitable candidate for participation in the study.
  9. Participants with cancer, having a life expectancy of < 12 months.
  10. Current diagnosis of or any other clinically significant indication of active sepsis
  11. Pregnant or lactating women.
  12. Have participated in any other investigational drug trial within 30 days of dosing or 5 half-lives (whichever is longer) in the current study.

    -


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05785819


Contacts
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Contact: Michael S Hanna, MD 301-360-3502 mhanna@veralox.com
Contact: Alicia Herr, PMP 301-360-3502 aherr@veralox.com

Locations
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United States, Pennsylvania
Thomas Jefferson University Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Ruben Rhoades, MD    215-955-8455    Ruben.Rhoades@jefferson.edu   
Sponsors and Collaborators
Veralox Therapeutics
Investigators
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Study Chair: John Alexander, MD Duke Clinical Research Institute
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Responsible Party: Veralox Therapeutics
ClinicalTrials.gov Identifier: NCT05785819    
Other Study ID Numbers: VLX-1005-003
First Posted: March 27, 2023    Key Record Dates
Last Update Posted: September 29, 2023
Last Verified: March 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Veralox Therapeutics:
Heparin
Thrombocytopenia
Platelets
Additional relevant MeSH terms:
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Thrombocytopenia
Purpura, Thrombocytopenic, Idiopathic
Blood Platelet Disorders
Hematologic Diseases
Cytopenia
Purpura, Thrombocytopenic
Purpura
Blood Coagulation Disorders
Thrombotic Microangiopathies
Hemorrhagic Disorders
Autoimmune Diseases
Immune System Diseases
Hemorrhage
Pathologic Processes
Skin Manifestations
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action