临床试验/NCT05152420

NCT05152420已完成1 期

A Randomised, Double-Blind, Placebo-Controlled, Single Ascending Dose Trial to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Intravenously Administered VMX-C001 in Healthy Subjects (Part 1) and in Combination With Selected Direct Oral Anticoagulants (DOACs) in Healthy Older Subjects (Part 2)

VarmX B.V.1 个研究点分布在 1 个国家目标入组 105 人开始时间: 2021年10月29日最近更新: 2023年6月2日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方
入组人数: 105
试验地点: 1
主要终点: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] (Part 2)

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

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.

研究设计

研究类型: Interventional
分配方式: Randomized
干预模型: Parallel
主要目的: Treatment
盲法: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

盲法说明

Double-blind

入排标准

年龄范围: 18 Years 至 79 Years（Adult, Older Adult）
性别: All
接受健康志愿者: 是

入选标准

•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 -
•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 -
•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.

排除标准

•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.
•any intracranial hemorrhage.
•uncontrolled severe hypertension.
•The participant has, in the opinion of the Principal Investigator, any increased risk of thrombosis or thromboembolism including any known thrombophilia, such as antiphospholipid syndrome, or any past history of thrombosis.
•The participant has a significant history of drug allergy, as determined by the Principal Investigator.
•The participant has, at Screening or on Day -1, a supine blood pressure or supine pulse rate ≥ 150/95 mmHg and 100 beats per minute (bpm), respectively, or < 90/40 mmHg and 40 bpm, respectively, confirmed by a repeat assessment.
•The participant consumes >21 alcoholic drinks/week for men or >14 alcoholic drinks/week for women (one unit of alcohol equals ½ pint [285 mL] of beer or lager, one glass [125 mL] of wine, or 1 measure [25 mL] of spirits), or has a significant history of alcoholism or drug/chemical abuse, as determined by the Principal Investigator for Part
•For Part 2, the participant consumes >7 alcoholic drinks/week.
•The participant has a positive urine drug screen, alcohol breath test or cotinine test results at Screening or on Day -1, confirmed by repeat testing.
•The female participant has a positive pregnancy test at Screening or on Day -1 or is lactating.
•The participant currently smokes or uses nicotine-containing products. Former smokers will be eligible, provided participants have not smoked for at least 3 months prior to administration of the study drug.
•The participant has, or has a history of, any clinically significant neurological, gastrointestinal, renal, hepatic, cardiovascular, psychiatric, respiratory, metabolic, endocrine, hematological or other major disorders, as determined by the Principal Investigator.
•The participant has a positive Hepatitis B surface antigen (HBsAg), Hepatitis C antibody, or human immunodeficiency virus (HIV) antibody test result at Screening.
•The participant has an abnormality in the 12-lead ECG at Screening or on Day -1 that, in the judgement of the Principal Investigator may, during the study, interfere with the interpretation of 12-lead ECG results, including average QTcF interval >450 msec for men or >470 msec for women, 2nd or 3rd degree atrioventricular block, complete left bundle branch block, complete right bundle branch block or Wolff-Parkinson-White Syndrome, defined as average PR<110 msec, confirmed by a triplicate repeat ECG.
•The participant has any other condition that, in the opinion of the Principal Investigator, would compromise the safety of the participant or the participant's ability to comply with the protocol and complete the study.
•The participant has renal insufficiency (serum creatinine level > 1.25 times upper limit of normal (ULN) or estimated glomerular filtration rate (eGFR) of ≤60 mL/minute).
•The participant has active liver disease (ALT/ aspartate aminotransferase (AST) >1.5x ULN, total bilirubin > 1.5x ULN at Screening or on Day -
•One re-test is allowed).
•Additional exclusion criteria for Part 2 only:
•Because of an effect on DOACs,participants are to be excluded if he/she receives or has received medication that is an inhibitor of P-glycoprotein or CYP3A
•(eg clarithromycin, erythromycin and azole-antimycotics such as ketoconazole, itraconazole, voriconazole and osaconazole or HIV protease inhibitors.) within 30 days prior to first administration of DOAC.
•Because of an effect on DOACs, participants are to be excluded if he/she receives or has received treatment with CYP3A4 inducers (eg St. John's wort, rifampicin, phenytoin, carbamazepine, phenobarbital within 30 days prior to first administration of DOAC.
•Because of an effect on DOACs, participants are to be excluded if he/she receives or has received treatment with selective serotonin reuptake inhibitors (SSRIs) or selective noradrenaline reuptake inhibitors (SNRIs) within 30 days prior to first administration of DOAC.
•The participant has any contra-indication to treatment with DOACs.

研究组 & 干预措施

Part 1 - Cohort 6

Experimental

Single dose cohort

干预措施: Placebo (Drug)

Part 1 - Cohort 2

Experimental

Single dose cohort

干预措施: Placebo (Drug)

Part 1 - Cohort 1

Experimental

Single dose cohort

干预措施: VMX-C001 (Drug)

Part 1 - Cohort 1

Experimental

Single dose cohort

干预措施: Placebo (Drug)

Part 1 - Cohort 2

Experimental

Single dose cohort

干预措施: VMX-C001 (Drug)

Part 1 - Cohort 3

Experimental

Single dose cohort

干预措施: VMX-C001 (Drug)

Part 1 - Cohort 3

Experimental

Single dose cohort

干预措施: Placebo (Drug)

Part 1 - Cohort 4

Experimental

Single dose cohort

干预措施: VMX-C001 (Drug)

Part 1 - Cohort 4

Experimental

Single dose cohort

干预措施: Placebo (Drug)

Part 1 - Cohort 5

Experimental

Single dose cohort

干预措施: VMX-C001 (Drug)

Part 1 - Cohort 5

Experimental

Single dose cohort

干预措施: Placebo (Drug)

Part 1 - Cohort 6

Experimental

Single dose cohort

干预措施: VMX-C001 (Drug)