A Study to Evaluate ART101 in Adult Participants With Hypertension

NCT06780033 | Terminated Phase 1 DMC

• 1 other identifier: ART101-C101
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Hypertension

Outcome Measures

Primary Outcomes (3)

• Assess safety of ART101 by the incidence of adverse events, adverse events of special interest and SAEs

  Up to Day 365 post first dose administration

• Number of participants with abnormal laboratory values and/or adverse events that are related to treatment

  Fasting serum chemistry, fasting hematology, fasting coagulation, fasting LFTs, fasting lipid panel, fasting glycemic assessment, urinalysis will be assessed.

  Up to Day 365 post first dose administration

• Change in pharmacodynamics of ART101 by noting change from baseline of serum angiotensinogen.

  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.

Secondary Outcomes (9)

• 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

Study Arms (2)

ART101 SAD

EXPERIMENTAL

Participants will receive single subcutaneously of ART101 or placebo on day 1 following a minimum of 8-hour fast.

Drug: ART-101 - SAD

Placebo

PLACEBO COMPARATOR

Participants will receive a single dose subcutaneously of placebo on day 1 following a minimum of 8-hour fast.

Other: Placebo

Interventions

ART-101 - SAD DRUG

Forty participants will be enrolled across 5 SAD cohorts. The planned doses across 5 cohorts are as follows- include 20mg (SAD Cohort 1), 60mg (SAD Cohort 2). 150mg (SAD Cohort 3). 300mg (SAD Cohort 4) and 500 mg (SAD Cohort 5).

ART101 SAD

Placebo OTHER

Participants will receive matching placebo subcutaneously on Day 1 after 8 hour fast.

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Arnatar Therapeutics, Inc.: lead

Study Sites (3)

University of Sunshine Coast

Morayfield, Queensland, 4506, Australia

Location

CMAX Clinical Research Central

Adelaide, South Australia, 5000, Australia

Location

CMAX Clinical Research Fusion

Norwood, South Australia, 5067, Australia

Location

MeSH Terms

Conditions

Hypertension

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2025
• First Posted: January 17, 2025
• Study Start: March 17, 2025
• Primary Completion: April 30, 2025
• Study Completion: April 30, 2025
• Last Updated: September 22, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

AU (3)