Effects of VMX-C001 on the Anticoagulant Effect of Different Forms of Heparin

NCT06517563 | Active Not Recruiting Phase 1

• 2 other identifiers: VMX-C001-022022-003675-41
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

A single centre, open-label study to assess the effects of VMX-C001 in combination with an oral FXa DOAC on the efficacy of Unfractionated Heparin (UFH) and of VMX-C001 alone on the efficacy of Low Molecular Weight Heparin (LMWH) in healthy subjects conducted in two parts: UFH cohort: Subjects will be administered 2 single doses of 5000 IU UFH i.v. on Day 1 and Day 5, oral doses of the DOAC Rivaroxaban once daily from Day 2 until the morning of Day 5, and one single dose of 170 mg VMX-C001 i.v. on Day 5. LMWH cohort: Subjects will be administered 2 single doses of 40 mg Enoxaparin s.c. on Day 1 and Day 4, and one single dose of 170 mg VMX-C001 i.v. on Day 4.

Conditions

Coagulation Disorder

Keywords

Direct oral anticoagulant (DOAC); Human coagulation factor X

Outcome Measures

Primary Outcomes (9)

• Change in thrombin time following dosing with VMX-C001(UFH cohort)

  Change from baseline in thrombin time

  Up to Day 6

• Change in prothrombin time (PT) following dosing with VMX-C001

  Change from baseline in PT

  Up to End of Study (Day 32/33)

• Change in activated partial thromboplastin time (aPTT) following dosing with VMX-C001

  Change from baseline in aPTT

  Up to End of Study (Day 32/33)

• Change in fibrinogen following dosing with VMX-C001

  Change from baseline in fibrinogen

  Up to End of Study (Day 32/33)

• Change in dilute Russell viper venom time (dRVVT) following dosing with VMX-C001(UFH Cohort only)

  Change from baseline in dRVVT

  Up to Day 6

• Change in dilute prothrombin time (dPT) following dosing with VMX-C001 (UFH Cohort only)

  Change from baseline in dPT

  Up to Day 6

• Change in thrombin generation following dosing with VMX-C001

  Change from baseline in thrombin generation measured by calibrated automated thrombography

  Up to Day 6

• Change in real time activated clotting time (ACT) following dosing with VMX-C001 (UFH cohort only)

  Change from baseline in ACT

  Up to Day 6

• Change in anti-factor 10a (FXa) activity following dosing with VMX-C001 (LMWH Cohort only)

  Change from baseline in anti-FXa activity

  Up to Day 6

Study Arms (2)

UFH Cohort

EXPERIMENTAL

Subjects will be administered 2 single doses of 5000 IU UFH i.v. on Day 1 and Day 5, oral doses of the DOAC Rivaroxaban QD from Day 2 until the morning of Day 5, and one single dose of 170 mg VMX-C001 i.v. on Day 5.

Drug: VMX-C001; Drug: Rivaroxaban; Drug: UFH

LMWH Cohort

EXPERIMENTAL

Subjects will be administered 2 single doses of 40 mg Enoxaparin s.c. on Day 1 and Day 4, and one single dose of 170 mg VMX-C001 i.v. on Day 4.

Drug: VMX-C001; Drug: Enoxaparin

Interventions

VMX-C001 DRUG

VMX-C001 is human factor X engineered to be insensitive to factor Xa DOACs

LMWH Cohort; UFH Cohort

Rivaroxaban DRUG

FXa Inhibitor

UFH Cohort

UFH DRUG

Unfractionated Heparin

UFH Cohort

Enoxaparin DRUG

Low Molecular Weight Heparin

LMWH Cohort

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Men and women of any ethnic origin aged between 18 and 49 years of age, inclusive, at the time of Screening.
• Male subjects must be willing to use appropriate contraception, such as a condom, and to refrain from sperm donation during the main study and until 90 days after study drug administration.
• Women of child-bearing potential must agree not to attempt to become pregnant and to use a highly effective form of birth control during the main study and for 90 days after study drug administration when their sexual partner has not been vasectomized. Highly effective forms of birth control entail the use of combined (estrogen- and progestogen-containing) or progestogen-only hormonal contraception associated with inhibition of ovulation, an intrauterine device (IUD), an intrauterine hormone-releasing system (IUS) or abstinence.
• Postmenopausal women must have had ≥12 months of spontaneous amenorrhea (with documented follicle stimulating hormone \[FSH\] \>33.4 IU/L).
• Surgically sterile women are defined as those who have had a surgical bilateral oophorectomy with or without hysterectomy, total hysterectomy or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, the reproductive status of the woman has to be confirmed by follow-up hormone level assessment. Women who are surgically sterile must provide documentation of the procedure by an operative report or by ultrasound.
• Subject must weigh between 60 and 120 kg, inclusive, and must have a BMI between 18.0 and 30.0 kg/m2, inclusive, at Screening and on Day -1.
• Subject must be in good health, as determined by a medical history, physical examination, 12-lead ECG and clinical laboratory evaluations (congenital non hemolytic hyperbilirubinemia is acceptable).
• Subject is willing and able to give their written informed consent to participate in the study and to abide by the study restrictions.
• Subject has good upper limb venous access.

You may not qualify if:

• The subject has taken tenoxicam in the 35 days prior to Day 1 or has taken piroxicam in the two weeks prior to Day 1.
• The subject is receiving or requires, for any cause, any anticoagulant or antiplatelet therapy including warfarin, clopidogrel or aspirin or any other anticoagulant or antiplatelet agent or has used these therapies in the 4 weeks prior to Day 1.
• The subject has taken any non-aspirin, non-tenoxicam, non-piroxicam non-steroidal antiinflammatory drug (NSAID) in the week prior to Day 1.
• The subject requires or has taken during the 4 weeks prior to Day 1, vitamin K for therapeutic reasons. Vitamin K not taken for therapeutic purposes is acceptable, e.g. as part of a multivitamin supplement.
• The subject has received any prescribed oral, systemic or topical medication, including any vaccinations, within 14 days before Day 1 (with the exception of contraceptives), unless in the opinion of the Principal Investigator and the Medical Monitor the medication will not interfere with the study procedures or compromise safety.
• The subject has used any non-prescribed systemic or topical medication (including herbal remedies) within 4 days prior to Day 1 (with the exception of oral vitamin/mineral supplements \[including those that contain vitamin K when not taken for therapeutic purposes\] and paracetamol), unless in the opinion of the Principal Investigator and the Medical Monitor the medication will not interfere with the study procedures or compromise safety.
• The subject has been administered an investigational drug (new chemical or biological entity) within 4 weeks prior to Day 1 for small molecules or within 12 weeks or 5 halflives, whichever is longer, prior to Day 1 for all other types of investigational drug.
• The subject has donated ≥500 mL blood, plasma or platelets in the 12 weeks prior to Screening or the subject has donated any blood amount within 30 days prior to Screening.
• Because of an increased risk of thrombosis, subjects with known diabetes mellitus or a fasted glucose ≥7.0 mmol/l at Screening.
• The subject has any bleeding diathesis, any increased risk of bleeding or, in the opinion of the Principal Investigator, is at increased risk of the consequences of bleeding including but not limited to the following:
• gastro-intestinal ulceration within the last 12 weeks;
• known or suspected oesophageal varices;
• vascular aneurysms or known arteriovenous malformations;
• history of known major intraspinal or intracerebral vascular abnormalities;
• history of brain, spinal or ophthalmic surgery within the last year;

Sponsors & Collaborators

• VarmX B.V.: lead

Study Sites (1)

ICON

Groningen, 9728 NZ, Netherlands

Location

MeSH Terms

Conditions

Hemostatic Disorders

Interventions

Rivaroxaban; Enoxaparin

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2024
• First Posted: July 24, 2024
• Study Start: August 14, 2024
• Primary Completion: December 9, 2024
• Study Completion (Estimated): October 1, 2026
• Last Updated: September 10, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)