Placebo-controlled Study of Single and Multiple Ascending Doses of UDP-003 in Healthy Human Participants and Followed by an Open-label Patient Cohort (CTx-001)

A Double Blind, Placebo-controlled Study in Healthy Participants to Investigate the Safety, Pharmacokinetics and Pharmacodynamics of Single and Multiple Ascending Doses of UDP-003 and Followed by an Open-label Multiple-dose Patient Cohort

The goal of this clinical trial is to learn if UDP-003 is safe in healthy human participants and patients, assess the pharmacokinetics (PK)/pharmacodynamics (PD) of UDP-003 in healthy human participants and patients and its potential efficacy in patients.

Researchers will compare UDP-003 to a placebo in a blinded manner.

This first in human, randomised, double-blind, placebo-controlled, prospective, single-centre trial with a modular dose-finding design will be conducted in 3 parts:

• Part 1: 6 cohorts of 6 healthy participants receiving Single Ascending Doses (SADs),
• Part 2: 3 cohorts of 12 healthy participants receiving Multiple Ascending Doses (MADs) (6 doses over 16 days),
• Part 3: 1 cohort of up to 9 evaluable participants diagnosed with acute coronary syndrome (ACS; non-ST elevation myocardial infarction [NSTEMI] or unstable angina) at least 12 months post-event receiving multiple doses (6 administrations of the 25 mg/kg dose over 6 weeks).

The planned duration of the study for each participant will be:

• 4 weeks for SAD Participants (1-day treatment period, 4-week safety follow-up)
• 6 weeks for MAD Participants (16-day treatment period,4-week safety follow-up)
• 180 Days for MD Patients (6-week treatment period, 6-month safety follow-up) Prior to participants being randomised to panels of increasing doses, all safety data will be reviewed for completed panels.

Study Overview

• Status: Recruiting
• Conditions: Atherosclerotic Cardiovascular Disease; Acute Coronary Syndromes
• Intervention / Treatment: Drug: UDP-003; Other: Placebo

Detailed Description

This trial's objective will be to collect the preliminary clinical safety and clinical pharmacology data. The study objective in the patient cohort is obtaining preliminary information on the safety of UDP-003 in those carrying a detectable plaque burden and obtaining preliminary indication of efficacy in respect to reducing the plaque burden.

This first in human, randomised, double-blind, placebo-controlled, prospective, single-centre trial with a modular dose-finding design will be conducted in 3 parts:

• Part 1: 6 cohorts of 6 healthy participants receiving SADs,
• Part 2: 3 cohorts of 12 healthy participants receiving MADs (6 doses over 16 days),
• Part 3: 1 cohort of 12 participants diagnosed with acute coronary syndrome (ACS; non-ST elevation myocardial infarction [NSTEMI] or unstable angina) at least 12 months post-event receiving multiple doses (6 administrations of the 25 mg/kg dose over 6 weeks). The SAD part will include healthy participants randomised to either active or placebo with a 2:1 ratio (24 active, 12 placebo) and the MAD parts with a 3:1 ratio (27 active, 9 placebo), in addition to up to 12 MD patient cohort receiving UDP-003.

Prior to participants being randomised to panels of increasing doses, all safety data will be reviewed for completed panels. Within each dose group in the SAD portion of the study, sentinel dosing will be implemented wherein 2 participants (1 active, 1 placebo) will be dosed at least 24 hours before the remaining participants in the cohort. Dosing in the MAD portion of the study will commence only after the Data Safety Monitoring Committee (DSMC) reviews the safety data from the 5th (20 mg/kg) SAD cohort.

Investigational Products A. UDP-003, formulated as a sterile solution for injection, 300 mg/mL. Volume of administration is weight dependent and target doses are 1-25 mg/kg.

B. Placebo formulated as sterile solution for injection. Volume injected will match the volumes of UDP-003 for each panel and each participant.

The investigational products will be administered as intravenous (IV) bolus push injection, in a blinded manner to sitting or supine participants. Doses lower than the highest dose will be diluted with vehicle (identical to placebo) to ensure the same dosing volume per body mass across placebo and active groups. No fasting is required.

In the MD panels, a single IV bolus push injection will be administered on Days 1, 8,15, 22, 29 and 36.

• Study Type: Interventional
• Enrollment (Estimated): 84
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Daniel M Clemens, Ph.D.; Phone Number: (707) 200-3610; Email: info@cyclaritytx.com
• Study Contact Backup: Name: Matthew O'Connor, Ph.D.; Phone Number: (707)200-3610; Email: info@cyclaritytx.com

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Recruiting
      • CMAX Clinical Research
      • Principal Investigator: Sepehr Shakib, PhD
      • Contact: Jane Kelly; Phone Number: +61(08)70887900; Email: cmax@cmax.com.au

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria

All Participants:

1. Participant understands study procedures and provides written informed consent for the trial.
2. Participant is able to comply with the protocol and the assessments therein.

Healthy Participants (SAD and MAD cohorts):

1. Healthy adult males and females, 18 to 65 years of age (inclusive) at the time of screening.
2. Adult males and females of body mass index (BMI) ≥ 18 and ≤ 32 kg/m² and body weight ≥ 50 and ≤ 120 kg.
3. Social smoking of less than 10 nicotine-containing products per month is acceptable. Absence of tobacco or nicotine containing product (including smoking cessation products) use, for a minimum of 2 weeks prior to dosing is required and will be confirmed by a negative cotinine test at check-in (one retest allowed at the discretion of the investigator).
4. Medically healthy with relevant renal parameters tests not exceeding 1.5 X the upper limits and no clinically significant screening results (e.g., laboratory profiles, medical history, vital signs, ECGs, physical examination) as deemed by the Principal Investigator; one retest is permitted at investigator discretion.

Participants with ACS (MD Patient cohort):

1. Adult males and females, 40 to 79 years of age (inclusive) at the time of screening, diagnosed with acute coronary syndrome (ACS), at least 12 months post event (NSTEMI or unstable angina).
2. Adult males and females of body mass index (BMI) ≥ 18
3. Medically stable with no clinically significant screening results (e.g., laboratory profiles including relevant renal parameters and liver function tests, medical history, vital signs, ECGs, physical examination) as deemed by the Principal Investigator.
4. Participants on a stable regimen and dose of ACS treatment including statins, anticoagulants, blood thinners, anti-platelets or other standard of care for 3 months prior to screening and for whom no change in this treatment is planned during the participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: UDP-003; UDP-003 will be administered to the participants randomised to this arm. UDP-003 is a formulated as a sterile solution for injection, 300 mg/mL. Volume of administration is weight dependent and target doses are 1-25 mg/kg.	Drug: UDP-003; The UDP-003 finished product is clear, colourless to yellow liquid that is intended to be a sterile solution for IV bolus push administration in sterile water at a concentration of 300 mg/mL.
Placebo Comparator: Placebo; Placebo will be administered to the participants randomised to this arm. Placebo formulated as sterile solution for injection. Volume injected will match the volumes of UDP-003 for each panel and each participant.	Other: Placebo; Placebo will be provided as a sterile clear, colourless solution formulated to match viscosity of the UDP-003 solution.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety outcome measures (Adverse Events)	Occurrence of adverse events (AEs) of any type and severity	From enrolment through 4 weeks for SAD Participants, 6 weeks for MAD Participants and 28 weeks for MD Patients
Safety outcome measures (Vital Signs: Systolic Blood Pressure)	SBP will be measured in mmHg	From enrolment through 4 weeks for SAD Participants, 6 weeks for MAD Participants and 28 weeks for MD Patients
Safety outcome measures (Vital Signs: Diastolic Blood Pressure)	DBP will be measured in mmHg	From enrolment through 4 weeks for SAD Participants, 6 weeks for MAD Participants and 28 weeks for MD Patients
Safety outcome measures (Vital signs: Heart Rate)	Heart Rate will be measured in bpm	From enrolment through 4 weeks for SAD Participants, 6 weeks for MAD Participants and 28 weeks for MD Patients
Safety outcome measures (Vital signs: Respiratory Rate)	RR will be measured in rpm	From enrolment through 4 weeks for SAD Participants, 6 weeks for MAD Participants and 28 weeks for MD Patients
Safety outcome measures (Vital signs: Temperature)	Body temperature will be measured in Celsius (0C)	From enrolment through 4 weeks for SAD Participants, 6 weeks for MAD Participants and 28 weeks for MD Patients
Safety outcome measures (Clinical Laboratory Parameters)	For parameters outside of the reference range an assessment of the significance (clinically significant / non-clinically significant) will be provided and all data outside the reference range of the clinical laboratory will be listed for all study participants	From enrolment through 4 weeks for SAD Participants, 6 weeks for MAD Participants and 28 weeks for MD Patients
Safety outcome measures (ECG QTCF Interval)	The QTcF interval will be calculated using the formula QTcF = QT/√R-R interval in seconds	From enrolment through 4 weeks for SAD Participants, 6 weeks for MAD Participants and 28 weeks for MD Patients
Safety outcome measures (Injection site reactions)	Assessment for signs of phlebitis, extravasation, infection and pain before, during and after intravenous administration is vital to ensure the patency and viability of the vein. The reactions will be assessed using the current FDA Toxicity Grading Scale provides a measure for classifying injection site AEs by four grades [Grade 1 (mild); Grade 2 (moderate); Grade 3 (severe) and Grade 4 (life threatening)].	From first dose administration (Day 1) through From enrolment through 4 weeks for SAD Participants, 6 weeks for MAD Participants and 28 weeks for MD Patients
Safety outcome measures (Audiometry: Self-evaluation questionnaire (THI))	Self-evaluation questionnaire: using Tinnitus Handicap Inventory [THI] questionnaire	From enrolment through 24 hours post dose for SAD Participants (Day 2), 24 hours post dose for MAD and MD Patients Participants (Day 17),
Safety outcome measures (Audiometry: Self-evaluation questionnaire (DHI))	Self-evaluation questionnaire: using Dizziness Handicap Inventory [DHI] questionnaire	From enrolment through 24 hours post dose for SAD Participants (Day 2), 24 hours post dose for MAD and MD Patients Participants (Day 17),
Safety outcome measures (Audiometry: PTA)	Air/Bone Pure-tone audiometry (PTA) conduction testing will be done at 250, 500, 1000, 3000, 4000, 6000 and 8000Hz	From enrolment through 24 hours post dose for SAD Participants (Day 2), 24 hours post dose for MAD and MD Patients Participants (Day 17),
Safety outcome measures (Audiometry: HFA)	Bone/Air High-frequency audiometry (HFA) conduction testing will be done at 9000, 10 000, 11200 and 12500Hz, Tympanometry, Self-evaluation questionnaires (tinnitus handicap inventory [THI] and dizziness handicap inventory [DHI])	From enrolment through 24 hours post dose for SAD Participants (Day 2), 24 hours post dose for MAD and MD Patients Participants (Day 17),

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics Outcome Measures (Cmax)	The maximum concentration achieved by UDP-003 in a specified compartment area of the body after the drug has been administered and before the administration of a second dose	Day 1 for the SAD and Days 1 and 16 for the multiple dosing parts
Pharmacokinetics Outcome Measures (Tmax)	Time at which maximum concentration of UDP is reached	Day 1 for the SAD and Days 1 and 16 for the multiple dosing parts
Pharmacokinetics Outcome Measures (half-life (t1/2))	The estimate of the time it takes for the concentration or amount in the body of that drug to be reduced by exactly one-half (50%).	Day 1 for the SAD and Days 1 and 16 for the multiple dosing parts
Pharmacokinetics Outcome Measures (AUC0-t and AUC0-inf)	Area under the concentration curve (AUC0-t and AUC0-inf) reflects the actual body exposure to drug after administration of a dose of the drug and is expressed in mg*h/L	Day 1 for the SAD and Days 1 and 16 for the multiple dosing parts
Pharmacokinetics Outcome Measures (Total Plasma Clearance (CL))	The volume of drug cleared from blood or plasma in unit time	Day 1 for the SAD and Days 1 and 16 for the multiple dosing parts
Pharmacokinetics Outcome Measures (Volume of Distribution (Vd))	The participant's drug's propensity to either remain in the plasma or redistribute to other tissue compartments	Day 1 for the SAD and Days 1 and 16 for the multiple dosing parts

Collaborators and Investigators

• Sponsor: Cyclarity Therapeutics, Inc.
• Collaborators: Monash University

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2025
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2027

Study Registration Dates

• First Submitted: January 13, 2025
• First Submitted That Met QC Criteria: February 3, 2025
• First Posted (Actual): February 6, 2025

Study Record Updates

• Last Update Posted (Actual): June 30, 2026
• Last Update Submitted That Met QC Criteria: June 26, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Atherosclerosis; Acute coronary syndrome; Healthy Participants; Cyclodextrin; 7-ketocholesterol (7KC); Plaque burden reduction
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Myocardial Ischemia; Atherosclerosis; Acute Coronary Syndrome
• Other Study ID Numbers: CTx-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No