NCT06780033终止1 期
A Phase 1, Randomized, Double-blind, Placebo Controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ART101 in Adult Participants With Hypertension.
Arnatar Therapeutics, Inc.3 个研究点 分布在 1 个国家目标入组 1 人开始时间: 2025年3月17日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 1
- 试验地点
- 3
- 主要终点
- Assess safety of ART101 by the incidence of adverse events, adverse events of special interest and SAEs
研究概览
简要总结
This is a Phase 1, first-in-human, randomized, double-blind, placebo-controlled, study to assess the safety, tolerability, Pharmacokinetics (PK), and pharmacodynamics (PD) of a single dose of ART101 administered via subcutaneous injection to hypertensive adult participants. An anticipated 5 dose cohorts (one as optional) with maximum of 40 participants will be randomized in SAD study.
详细描述
The study will be conducted across 5 single ascending dose (SAD) cohorts with approximately 40 participants.
Estimated study duration for each participant: Approximately 13.5 months including a 1.5-month Screening Period, 3-month Treatment Period and up to 12-month Follow-up post dose. On Day 1, participants will receive study drug as a single subcutaneous injection following a minimum 8-hour fast. The planned ART101 dose across 5 cohorts are as follows- 20mg, 60mg, 150mg, 300mg and 500mg. An SRC meeting will be held prior to dose escalations or prior to initiation of next cohort.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female (excluding women of child bearing potential [WOCBP]) aged 18 to 65 years (inclusive at the time of informed consent).
- •Hypertensive but otherwise in good general health, with no clinically significant medical history, and have no clinically significant abnormalities on physical examination at Screening and/or before the first administration of study drug at the discretion of the PI.
- •Either of the following:
- •Drug Naïve.
- •Has previously received monotherapy or dual therapy for hypertension but has ceased medication(s) under the supervision of the participant's medical professional eg, General Practitioner or Specialist.
- •Note: Where applicable, a participant must have ceased administering therapy for hypertension from ≥ 3 weeks prior to Screening.
- •Mean sitting SBP > 130 mmHg and ≤ 159 mmHg per USA guidelines at Screening (by oscillometric AOBP measurement).
- •Note: If the PI (or designee) considers that the Screening oscillometric AOBP measurement is spuriously elevated, oscillometric AOBP may be retested once during Screening.
- •Mean SBP > 130 mmHg and ≤ 159 mmHg from the daytime BP measurements and a night-time mean SBP ≥ 110mg Hg at Baseline per USA guidelines (assessed by 24-hour ABPM during the Screening Period) without hypertensive medication.
- •Note: Where the PI (or designee) is informed that the 24-hour ABPM has failed quality check, the 24-hour ABPM may be repeated once during the Screening Period.
- •BMI between ≥ 18.0 and ≤ 35.0 kg/m2 at Screening and weight ≥ 50 kg at Screening.
- •Nonsmoker and must not have used any nicotine-containing products within 6 months prior to Screening.
- •ECG findings at Screening within normal range, unless deemed not clinically significant by the PI or designee.
- •Males must be surgically sterile vasectomized since at least 6 months prior to first study drug administration, OR if not surgically sterile AND will engage in sexual relations with a WOCBP, his female partner must meet 1 of the following criteria:
- •Surgically sterile (eg, bilateral tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy, bilateral tubal ligation) or postmenopausal.
- •Agree to use acceptable, highly effective, double barrier contraception from Screening until study completion, including the Follow-up Period. Acceptable, highly effective, double barrier contraception is defined as meeting 1 of the following criteria:
- •i. Simultaneous use of hormonal contraceptives (implant, injection, pills, vaginal rings and skin patches) and must agree to use the same hormonal contraceptive throughout the study, and condom for the male participant.
- •ii. Simultaneous use of Intrauterine Device (IUD) or Intrauterine System (IUS) (Mirena or Kyleena) and condom for the male participant.
- •iii. Simultaneous use of diaphragm or cervical cap and male condom for the male participant.
- •Note: Males with same-sex partners (abstinence from penile-vaginal intercourse) or are abstinent from heterosexual intercourse are not required to use contraception when this is their preferred and usual lifestyle. Note: Males must be willing not to donate sperm from the first dose of study drug until at least 90 days after study completion.
- •Able and willing to comply with study procedures, study restrictions, and visits to the study site.
- •Able and willing to provide written informed consent after the nature of the study has been explained and prior to the commencement of any study procedures.
排除标准
- •WOCBP or female who is pregnant, breastfeeding, or planning to become pregnant during the study.
- •Mean sitting DBP > 110 mmHg at Screening (by oscillometric AOBP measurement) without hypertensive medication.
- •History of secondary hypertension including, but not limited to, any of the following:
- •Renovascular hypertension (unilateral or bilateral renal artery stenosis).
- •Coarctation of the aorta.
- •Primary hyperaldosteronism.
- •Cushing's disease, pheochromocytoma.
- •Polycystic kidney disease.
- •Drug induced hypertension.
- •Any of the following:
- •Postural tachycardia (ie, > 30 bpm upon standing).
- •Orthostatic hypotension (ie, a fall in SBP of ≥ 20 mmHg or DBP of ≥ 10 mmHg within 1 minute of standing up from a supine position).
- •History of hypotension.
- •Arm circumference does not align with any blood pressure cuff size. Note: Where applicable, a participant must have ceased administering monotherapy or dual therapy for hypertension from ≥ 3 weeks prior to Screening.
- •Note: The relevant Australian Product Information should be reviewed by the PI or designee to determine the appropriate washout period for a prescription medication.
- •Note: Cessation of prescription medication (eg, monotherapy or dual therapy for hypertension) by participant must occur with the approval of the participant's medical professional eg, General Practitioner or Specialist.
- •Diagnosed with diabetes mellitus.
- •Is participating in a concurrent experimental therapy study with a study drug or medical device.
- •Any of the following:
- •Has received experimental therapy with a small molecule within 30 days of the first administration of study drug or 5 half-lives of the small molecule experimental therapy (whichever is the longer). Note: Experimental therapy with a small molecule refers to any small molecule compound (eg, Lipitor, Benadryl) under investigation in a clinical trial.
- •Has received experimental therapy with a large molecule within 90 days of the first administration of study drug or 5 half-lives of the large molecule experimental therapy (whichever is the longer).
- •Note: Experimental therapy with a large molecule refers to a large molecule (eg, monoclonal antibodies, peptides) under investigation in a clinical trial.
- •Has received experimental therapy with antisense oligonucleotides or siRNA within 12 months of the first administration of study drug or 5 half-lives (whichever is longer).
- •Has participated in more than 4 experimental therapy studies with an experimental therapy or medical device within 1 year prior to first administration of study drug.
- •Has received any immune suppressing drug (including experimental therapies as part of a clinical study) within 4 months of the first administration of study drug or 5half-lives, whichever is longer.
- •Evidence or history of any clinically significant immunologic, hematologic, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, musculoskeletal, hepatic, psychiatric, neurologic, allergic disease (including clinically significant or multiple drug allergies), surgical conditions, or any condition that, in the opinion of the PI, that would jeopardize the safety of the participant, prevent complete participation in the study, or compromise interpretation of study data.
- •History of allergic reaction to an oligonucleotide, GalNAc-containing medication, or the study drug or its constituents.
- •History or presence of a condition associated with significant immunosuppression.
- •History of life-threatening infection (eg, meningitis).
- •History of malignancy, except for the following:
- •Basal or squamous cell carcinoma of the skin excised more than 2 years prior to Screening.
- •Cancer that has been resolved or has been in remission for more than 5 years prior to Screening.
- •History of porphyria, myopathy, cardiac valve repair, cardiac device implantation or an active liver disease (including steatotic hepatitis and fibrosis).
- •Has undergone surgical procedures within 4 weeks of Day -1, or is planning elective surgery until the angiotensinogen level has returned to >50% predose Baseline level or until at least Day 365 whichever comes first.
- •Unstable / underlying cardiovascular disease defined as:
- •Any history of congestive heart failure (New York Heart Association [NYHA] Class III-IV).
- •Any history of previous myocardial infarction, coronary revascularization, unstable or stable angina pectoris ˂ 6 months prior to Screening.
- •Any hemodynamically unstable atrial or ventricular arrhythmias.
- •Significant uncorrected valvular heart disease.
- •History of stroke or transient ischemic attack < 6 months prior to Screening.
- •A cardiac valve repair, cardiac device implantation, and/or a hospitalization for heart failure within 3 months of Screening.
- •Any of the following:
- •A personal or family history of long QT syndrome, Torsades de Pointes, or other complex ventricular arrhythmias, or family history of sudden death.
- •History of, or current, clinically significant arrhythmias as judged by the PI, including ventricular tachycardia, ventricular fibrillation, atrial fibrillation, sinus node dysfunction, or clinically significant heart block. Participants with minor forms of ectopy (eg, premature atrial contractions) are not necessarily excluded.
- •Abnormal ECG findings at Screening that are considered by the PI or designee to be clinically significant.
- •Any of the following:
- •Evidence of severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) infection at Screening. During the study, a participant with an infection may continue the study at the discretion of the PI.
- •Oral temperature > 38 °C on Day-
- •Has experienced fever (body temperature > 38°C) or symptomatic viral or bacterial infection within 2 weeks prior to Screening.
- •Has experienced any illness within 4 weeks of Day -1 deemed by the PI to be clinically significant.
- 另有 31 项未显示
研究组 & 干预措施
ART101 SAD
Experimental
Participants will receive single subcutaneously of ART101 or placebo on day 1 following a minimum of 8-hour fast.
干预措施: ART-101 - SAD (Drug)
Placebo
Placebo Comparator
Participants will receive a single dose subcutaneously of placebo on day 1 following a minimum of 8-hour fast.
干预措施: Placebo (Other)
结局指标
主要结局
Assess safety of ART101 by the incidence of adverse events, adverse events of special interest and SAEs
时间窗: Up to Day 365 post first dose administration
Number of participants with abnormal laboratory values and/or adverse events that are related to treatment
时间窗: Up to Day 365 post first dose administration
Fasting serum chemistry, fasting hematology, fasting coagulation, fasting LFTs, fasting lipid panel, fasting glycemic assessment, urinalysis will be assessed.
Change in pharmacodynamics of ART101 by noting change from baseline of serum angiotensinogen.
时间窗: Day 8, Day 15, Day 22, Day 29, Day 43, Day 57, Day 85 (~3 Months), Day 127, Day 169 (6 Months), Day 260 (9 Months) and Day 365 (12 Months) post first dose administration.
次要结局
- PK Parameters: Maximum Concentration (Cmax)(Samples will be collected at 9 timepoints from pre-dose on Day 1, 2 timepoints on Day 2 and Day 8 post dosing)
- PK Parameters: Time for maximum concentration (Tmax)(Samples will be collected at 9 timepoints from pre-dose on Day 1, 2 timepoints on Day 2 and Day 8 post dosing)
- PK Parameters: Area under the curve (AUC)(Samples will be collected at 9 timepoints from pre-dose on Day 1, 2 timepoints on Day 2 and Day 8 post dosing)
- PK Parameters- Elimination half-life (t½)(Samples will be collected at 9 timepoints from pre-dose on Day 1, 2 timepoints on Day 2 and Day 8 post dosing)
- PK parameters: Apparent terminal elimination rate (λz )(Samples will be collected at 9 timepoints from pre-dose on Day 1, 2 timepoints on Day 2 and Day 8 post dosing)
- PK parameters: Volume of distribution (Vz/F)(Samples will be collected at 9 timepoints from pre-dose on Day 1, 2 timepoints on Day 2 and Day 8 post dosing)
- Urine PK parameters: Renal Clearance (Ae)(Urine will be collected between 0 to 6 hours, 6 to 12 hours, 12 to 24 hours, 24 to 28 hours and Day 8 following study drug injection)
- Urine PK parameters: Fraction of drug excreted in urine (fe)(Urine will be collected between 0 to 6 hours, 6 to 12 hours, 12 to 24 hours, 24 to 28 hours and Day 8 following study drug injection)
- Urine PK parameters: Renal Clearance (CLr)(Urine will be collected between 0 to 6 hours, 6 to 12 hours, 12 to 24 hours, 24 to 28 hours and Day 8 following study drug injection)
研究者
研究点 (3)
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