Single Dose Trial of VMX-C001 in Healthy Subjects with and Without FXa Direct Oral Anticoagulant

NCT06372483 | Active Not Recruiting Phase 1 DMC

• 2 other identifiers: VMX-C001-032023-507059-32-00
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

A single centre, double-blind, randomized, placebo-controlled single dose study to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of VMX-C001, conducted in two parts: Part 1: Single dose of VMX-C001 or placebo in healthy volunteers. Part 2: Single dose of VMX-C001 or placebo in combination with a selected factor 10a (FXa) direct oral anticoagulant (DOAC) in healthy older subjects.

Conditions

Coagulation Disorder

Outcome Measures

Primary Outcomes (24)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] (Part 1)

  Number of Subjects with One of More Drug Related Adverse Events (AEs) or any Serious AEs

  From dosing up to Day 28

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] (Part 2)

  Number of Subjects with One of More Drug Related Adverse Events (AEs) or any Serious AEs

  From dosing up to Day 31

• PK of VMX-C001 in plasma - Cmax

  Maximal concentration in plasma

  Up to 7 days post VMX-C001 dose

• PK of VMX-C001 in plasma - tmax

  Time of maximal concentration in plasma

  Up to 7 days post VMX-C001 dose

• PK of VMX-C001 in plasma - t1/2

  Terminal elimination half-life in plasma

  Up to 7 days post VMX-C001dose

• PK of VMX-C001 in plasma - AUC0-last

  Area under the concentration-time curve from time of dosing to last measurable concentration in plasma

  Up to 7 days post VMX-C001 dose

• PK of VMX-C001 in plasma - AUC0-inf

  Area under the concentration-time curve from time of dosing extrapolated to infinity in plasma

  Up to 7 days post VMX-C001 dose

• PK of VMX-C001 in plasma - Lambda z

  Terminal elimination rate constant

  Up to 7 days post VMX-C001 dose

• PK of VMX-C001 in plasma - CL

  Total body clearance

  Up to 7 days post VMX-C001 dose

• PK of VMX-C001 in plasma - Vz

  Apparent volume of distribution

  Up to 7 days post VMX-C001 dose

• DOAC plasma concentrations (Part 2)

  Up to Day 10

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

  Up to 7 days post VMX-C001 dose

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

  Up to 7 days post VMX-C001 dose

• Change in D-dimer following dosing with VMX-C001

  Up to 7 days post VMX-C001 dose

• Change in prothrombin fragments F1 and 2 following dosing with VMX-C001

  Mean and median values, subjects on active treatment per group versus placebo

  Up to 7 days post VMX-C001 dose

• Change in thrombin generation, measured by lag time, following dosing with VMX-C001

  Mean and median values, subjects on active treatment per group versus placebo

  Up to 7 days post VMX-C001 dose

• Change in thrombin generation, measured by endogenous thrombin potential, following dosing with VMX-C001

  Mean and median values, subjects on active treatment per group versus placebo

  Up to 7 days post VMX-C001 dose

• Change in thrombin generation, measured by peak height, following dosing with VMX-C001

  Mean and median values, subjects on active treatment per group versus placebo

  Up to 7 days post VMX-C001 dose

• Change in thrombin generation, measured by time to peak, following dosing with VMX-C001

  Mean and median values, subjects on active treatment per group versus placebo

  Up to 7 days post VMX-C001 dose

• Change in thrombin generation, measured by velocity index, following dosing with VMX-C001

  Mean and median values, subjects on active treatment per group versus placebo

  Up to 7 days post VMX-C001 dose

• Change in thrombin generation, measured by time to tail, following dosing with VMX-C001

  Mean and median values, subjects on active treatment per group versus placebo

  Up to 7 days post VMX-C001 dose

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

  Up to 7 days post VMX-C001 dose

• Change in diluted Russell Viper Venom time (dRVVT) following dosing with VMX-C001

  Up to 7 days post VMX-C001 dose

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

  Up to 7 days post VMX-C001 dose

Secondary Outcomes (2)

• Antibodies against VMX-C001 in plasma

  Up to 28 days post VMX-C001 dose

• Antibodies against human coagulation FX in plasma

  Up to 28 days post VMX-C001 dose

Study Arms (10)

Part 1, Cohort 1:1 - VMX-C001

EXPERIMENTAL

Single dose active.

Drug: VMX-C001

Part 1, Cohort 1:1 - Placebo

PLACEBO COMPARATOR

Single dose placebo.

Drug: Placebo

Part 2, Cohort 2:1 - VMX-C001 + Rivaroxaban

EXPERIMENTAL

Single dose active in combination with DOAC.

Drug: VMX-C001; Drug: Rivaroxaban 20 mg Oral Tablet

Part 2, Cohort 2:1 - Placebo + Rivaroxaban

PLACEBO COMPARATOR

Single dose placebo in combination with DOAC.

Drug: Placebo; Drug: Rivaroxaban 20 mg Oral Tablet

Part 2, Cohort 2:2 - VMX-C001 + DOAC

EXPERIMENTAL

Optional cohort - Single dose active in combination with selected DOAC.

Drug: VMX-C001; Drug: Rivaroxaban 20 mg Oral Tablet; Drug: Apixaban 5 mg Oral Tablet; Drug: Edoxaban 60 mg Oral Tablet

Part 2, Cohort 2:2 - Placebo + DOAC

PLACEBO COMPARATOR

Optional cohort - Single dose placebo in combination with selected DOAC.

Drug: Placebo; Drug: Rivaroxaban 20 mg Oral Tablet; Drug: Apixaban 5 mg Oral Tablet; Drug: Edoxaban 60 mg Oral Tablet

Part 2, Cohort 2:3 - VMX-C001 + DOAC

EXPERIMENTAL

Optional cohort - Single dose active in combination with selected DOAC.

Drug: VMX-C001; Drug: Rivaroxaban 20 mg Oral Tablet; Drug: Apixaban 5 mg Oral Tablet; Drug: Edoxaban 60 mg Oral Tablet

Part 2, Cohort 2:3 - Placebo + DOAC

PLACEBO COMPARATOR

Optional cohort - Single dose placebo in combination with selected DOAC.

Drug: Placebo; Drug: Rivaroxaban 20 mg Oral Tablet; Drug: Apixaban 5 mg Oral Tablet; Drug: Edoxaban 60 mg Oral Tablet

Part 2, Cohort 2:4 - VMX-C001 + DOAC

EXPERIMENTAL

Optional cohort - Single dose active in combination with selected DOAC.

Drug: VMX-C001; Drug: Rivaroxaban 20 mg Oral Tablet; Drug: Apixaban 5 mg Oral Tablet; Drug: Edoxaban 60 mg Oral Tablet

Part 2, Cohort 2:4 - Placebo + DOAC

PLACEBO COMPARATOR

Optional cohort - Single dose placebo in combination with selected DOAC.

Drug: Placebo; Drug: Rivaroxaban 20 mg Oral Tablet; Drug: Apixaban 5 mg Oral Tablet; Drug: Edoxaban 60 mg Oral Tablet

Interventions

VMX-C001 DRUG

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

Part 1, Cohort 1:1 - VMX-C001; Part 2, Cohort 2:1 - VMX-C001 + Rivaroxaban; Part 2, Cohort 2:2 - VMX-C001 + DOAC; Part 2, Cohort 2:3 - VMX-C001 + DOAC; Part 2, Cohort 2:4 - VMX-C001 + DOAC

Placebo DRUG

VMX-C001 matched placebo

Part 1, Cohort 1:1 - Placebo; Part 2, Cohort 2:1 - Placebo + Rivaroxaban; Part 2, Cohort 2:2 - Placebo + DOAC; Part 2, Cohort 2:3 - Placebo + DOAC; Part 2, Cohort 2:4 - Placebo + DOAC

Rivaroxaban 20 mg Oral Tablet DRUG

Fxa DOAC

Part 2, Cohort 2:1 - Placebo + Rivaroxaban; Part 2, Cohort 2:1 - VMX-C001 + Rivaroxaban; Part 2, Cohort 2:2 - Placebo + DOAC; Part 2, Cohort 2:2 - VMX-C001 + DOAC; Part 2, Cohort 2:3 - Placebo + DOAC; Part 2, Cohort 2:3 - VMX-C001 + DOAC; Part 2, Cohort 2:4 - Placebo + DOAC; Part 2, Cohort 2:4 - VMX-C001 + DOAC

Apixaban 5 mg Oral Tablet DRUG

Fxa DOAC

Part 2, Cohort 2:2 - Placebo + DOAC; Part 2, Cohort 2:2 - VMX-C001 + DOAC; Part 2, Cohort 2:3 - Placebo + DOAC; Part 2, Cohort 2:3 - VMX-C001 + DOAC; Part 2, Cohort 2:4 - Placebo + DOAC; Part 2, Cohort 2:4 - VMX-C001 + DOAC

Edoxaban 60 mg Oral Tablet DRUG

Fxa DOAC

Part 2, Cohort 2:2 - Placebo + DOAC; Part 2, Cohort 2:2 - VMX-C001 + DOAC; Part 2, Cohort 2:3 - Placebo + DOAC; Part 2, Cohort 2:3 - VMX-C001 + DOAC; Part 2, Cohort 2:4 - Placebo + DOAC; Part 2, Cohort 2:4 - VMX-C001 + DOAC

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In Part 1, men and women of any ethnic origin between 18 and 49 years of age, in Part 2, men and women of any ethnic origin between 50 and 79 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 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 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 the first administration of study drug or FXa DOAC or has taken piroxicam in the two weeks prior to the first administration of study drug or FXa DOAC.
• The subject has taken any non-aspirin, non-piroxicam, non-steroidal anti-inflammatory drug (NSAID) in the week prior to the first administration of study drug or FXa DOAC.
• The subject requires or has taken during the month prior to first administration of study drug or FXa DOAC, vitamin K for therapeutic reasons. Vitamin K not taken for therapeutic purposes is acceptable, e.g., as part of a multivitamin supplement.
• 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 month prior to the first administration of study drug or FXa DOAC.
• The subject has received any prescribed oral, systemic or topical medication, including any vaccinations, within 14 days prior to the first administration of study drug or FXa DOAC (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 one week prior to the first administration of study drug or FXa DOAC (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 is currently participating in a clinical study, e.g. attending follow-up visits or has been administered an investigational drug (new chemical or biological entity) within 1 month (for small molecules) or 3 months (for biologicals) prior to administration of the study drug.
• The subject has donated ≥500 mL blood, plasma, or platelets in the 3 months prior to Screening or any other 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 3 months;
• 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; apixaban; Tablets; edoxaban

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; Dosage Forms; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Placebo controlled, single dose.

Study Record Dates

• First Submitted: March 15, 2024
• First Posted: April 18, 2024
• Study Start: February 21, 2024
• Primary Completion: August 7, 2024
• Study Completion (Estimated): August 1, 2026
• Last Updated: November 18, 2024

Record last verified: 2024-11

Locations

NL (1)