Study of Intravenous VMX-C001 in Healthy Subjects and in Combination With Selected Direct Oral Anticoagulants in Healthy Older Subjects

NCT05152420 | Completed Phase 1

• 1 other identifier: VMX-C001-01
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 1

Brief Summary

A single centre, double-blind, randomized, parallel group, placebo-controlled study in healthy subjects conducted in two parts: Part 1: Single ascending doses in healthy subjects aged 18 to 49 years to assess safety, pharmacokinetics (PK) and pharmacodynamic (PD) effects of VMX-C001. Part 2: Healthy subjects aged 50 to 79 years to assess safety, PK and PD effects of VMX-C001 in the presence of DOACs.

Conditions

Coagulation Disorder

Keywords

Direct oral anticoagulant (DOAC); Human coagulation factor X

Outcome Measures

Primary Outcomes (13)

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

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

  Up to Day 28

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

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

  Up to Day 31

• PK of VMX-C001 in plasma after single dose administration - Cmax (Part 1)

  Maximal concentration

  Up to Day 7

• PK of VMX-C001 in plasma after single dose administration - tmax (Part 1)

  Time of maximal concentration

  Up to Day 7

• PK of VMX-C001 in plasma after single dose administration - t1/2 (Part 1)

  Terminal elimination half-life

  Up to Day 7

• PK of VMX-C001 in plasma after single dose administration - AUC0-last (Part 1)

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

  Up to Day 7

• PK of VMX-C001 in plasma after single dose administration - AUC0-inf (Part 1)

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

  Up to Day 7

• PK of VMX-C001 in plasma after single dose administration - Lambda z (Part 1)

  Terminal elimination rate constant

  Up to Day 7

• PK of VMX-C001 in plasma after single dose administration - CL (Part 1)

  Total body clearance

  Up to Day 7

• PK of VMX-C001 in plasma after single dose administration - Dose proportionality (Part 1)

  Up to Day 7

• Change in D-dimer, Thrombin-Antithrrombin complexes and prothrombin fragments F1 and F2 following dosing with VMX-C001 (Part 1 and Part 2)

  Up to Day 28 post dose with VMX-C001

• Change from baseline in thrombin generation (ETP) following dosing with VMX-C001 in subjects previously dosed with DOAC anticoagulants (Part 2)

  Up to 24 hours post dose with VMX-C001

• DOAC plasma concentrations (Part 2)

  Up to Day 5

Secondary Outcomes (4)

• Antibodies against VMX-C001 in plasma (Part 1)

  Up to Day 28

• Antibodies against VMX-C001 in plasma (Part 2)

  Up to Day 31

• Antibodies against human coagulation FX in plasma (Part 1)

  Up to Day 28

• Antibodies against human coagulation FX in plasma (Part 2)

  Up to Day 31

Study Arms (13)

Part 1 - Cohort 1

EXPERIMENTAL

Single dose cohort

Drug: VMX-C001; Drug: Placebo

Part 1 - Cohort 2

EXPERIMENTAL

Single dose cohort

Drug: VMX-C001; Drug: Placebo

Part 1 - Cohort 3

EXPERIMENTAL

Single dose cohort

Drug: VMX-C001; Drug: Placebo

Part 1 - Cohort 4

EXPERIMENTAL

Single dose cohort

Drug: VMX-C001; Drug: Placebo

Part 1 - Cohort 5

EXPERIMENTAL

Single dose cohort

Drug: VMX-C001; Drug: Placebo

Part 1 - Cohort 6

EXPERIMENTAL

Single dose cohort

Drug: VMX-C001; Drug: Placebo

Part 2 - Cohort 1

EXPERIMENTAL

Single dose cohort of selected FXa DOAC anticoagulant in combination with VMX-C001

Drug: VMX-C001; Drug: Placebo; Drug: Apixaban; Drug: Rivaroxaban; Drug: Edoxaban

Part 2 - Cohort 2

EXPERIMENTAL

Single dose cohort of selected FXa DOAC anticoagulant in combination with VMX-C001

Drug: VMX-C001; Drug: Placebo; Drug: Apixaban; Drug: Rivaroxaban; Drug: Edoxaban

Part 2 - Cohort 3

EXPERIMENTAL

Single dose cohort of selected FXa DOAC anticoagulant in combination with VMX-C001

Drug: VMX-C001; Drug: Placebo; Drug: Apixaban; Drug: Rivaroxaban; Drug: Edoxaban

Part 2 - Cohort 4

EXPERIMENTAL

Single dose cohort of selected FXa DOAC anticoagulant in combination with VMX-C001

Drug: VMX-C001; Drug: Placebo; Drug: Apixaban; Drug: Rivaroxaban; Drug: Edoxaban

Part 2 - Cohort 5

EXPERIMENTAL

Single dose cohort of selected FXa DOAC anticoagulant in combination with VMX-C001

Drug: VMX-C001; Drug: Placebo; Drug: Apixaban; Drug: Rivaroxaban; Drug: Edoxaban

Part 2 - Cohort 6

EXPERIMENTAL

Single dose cohort of selected FXa DOAC anticoagulant in combination with VMX-C001

Drug: VMX-C001; Drug: Placebo; Drug: Apixaban; Drug: Rivaroxaban; Drug: Edoxaban

Part 2 - Cohort 7

EXPERIMENTAL

Single dose cohort of selected FXa DOAC anticoagulant in combination with VMX-C001

Drug: VMX-C001; Drug: Placebo; Drug: Apixaban; Drug: Rivaroxaban; Drug: Edoxaban

Interventions

VMX-C001 DRUG

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

Part 1 - Cohort 1; Part 1 - Cohort 2; Part 1 - Cohort 3; Part 1 - Cohort 4; Part 1 - Cohort 5; Part 1 - Cohort 6; Part 2 - Cohort 1; Part 2 - Cohort 2; Part 2 - Cohort 3; Part 2 - Cohort 4; Part 2 - Cohort 5; Part 2 - Cohort 6; Part 2 - Cohort 7

Placebo DRUG

VMX-C001 matched placebo

Part 1 - Cohort 1; Part 1 - Cohort 2; Part 1 - Cohort 3; Part 1 - Cohort 4; Part 1 - Cohort 5; Part 1 - Cohort 6; Part 2 - Cohort 1; Part 2 - Cohort 2; Part 2 - Cohort 3; Part 2 - Cohort 4; Part 2 - Cohort 5; Part 2 - Cohort 6; Part 2 - Cohort 7

Apixaban DRUG

FXa Inhibitor

Part 2 - Cohort 1; Part 2 - Cohort 2; Part 2 - Cohort 3; Part 2 - Cohort 4; Part 2 - Cohort 5; Part 2 - Cohort 6; Part 2 - Cohort 7

Rivaroxaban DRUG

FXa Inhibitor

Part 2 - Cohort 1; Part 2 - Cohort 2; Part 2 - Cohort 3; Part 2 - Cohort 4; Part 2 - Cohort 5; Part 2 - Cohort 6; Part 2 - Cohort 7

Edoxaban DRUG

FXa Inhibitor

Part 2 - Cohort 1; Part 2 - Cohort 2; Part 2 - Cohort 3; Part 2 - Cohort 4; Part 2 - Cohort 5; Part 2 - Cohort 6; Part 2 - Cohort 7

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 aged between 18 and 49 years of age, inclusive, at the time of Screening.
• In Part 2, men and women of any ethnic origin aged 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) ≥30 milli-International units (mIU)/mL).
• 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.
• All women must have a negative pregnancy test result at Screening and on Day -1.
• Subject must weigh between 60 and 120 kg, inclusive, and must have a BMI between 18.0 and 30.0 kg/m\^2, 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).
• Participant is willing and able to give their written informed consent to participate in the study and to abide by the study restrictions.
• Participant has good upper limb venous access.

You may not qualify if:

• The participant has taken piroxicam in the two weeks prior to the first administration of study drug or DOAC.
• The participant has taken any non-aspirin non-piroxicam NSAID in the week prior to the first administration of study drug or DOAC.
• The participant requires or has taken during the month prior to first administration of study drug or DOAC, vitamin K for therapeutic reasons. Vitamin K not taken for therapeutic purposes is acceptable, e.g. as part of a multivitamin supplement.
• The participant 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 DOAC.
• The participant has received any prescribed oral, systemic or topical medication, including coronavirus disease (COVID)-19 vaccination, within 14 days prior to the first administration of study drug or 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 participant has used any non-prescribed systemic or topical medication (including herbal remedies) within one week prior to the first administration of study drug or DOAC (with the exception of oral vitamin/mineral supplements (that do not contain vitamin k) 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 participant 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) in the 3 months prior to administration of the study drug.
• The participant has donated \>500 mL blood, plasma or platelets in the 3 months prior to Screening.
• Because of an increased risk of thrombosis participants with known diabetes mellitus or a fasted glucose ≥7.0 mmol/l at Screening.
• The participant 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)

QPS Netherlands B.V.

Groningen, 9713 GZ, Netherlands

Location

MeSH Terms

Conditions

Hemostatic Disorders

Interventions

apixaban; Rivaroxaban; 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

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 ascending dose.

Study Record Dates

• First Submitted: November 17, 2021
• First Posted: December 9, 2021
• Study Start: October 29, 2021
• Primary Completion: February 3, 2023
• Study Completion: February 3, 2023
• Last Updated: June 2, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)