Clinical trial NCT06813339: Placebo-controlled Study of Single and Multiple Ascending Doses of UDP-003 in Healthy Human Participants and Patients
Official title: A Double Blind, Placebo-controlled Study to Investigate the Safety, Pharmacokinetics and Pharmacodynamics of Single and Multiple Ascending Doses of UDP-003 in Healthy Human Participants and Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Atherosclerotic Cardiovascular Disease
Acute Coronary Syndromes
Keywords: Atherosclerosis
7-ketocholesterol (7KC)
Cyclodextrin
Plaque burden reduction
Healthy Participants
Acute coronary syndrome
Lead sponsor: Cyclarity Therapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Monash University
First posted: 2025-02-06
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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 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 16 days).

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)
* 28 weeks for MD Patients (16-day 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.

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 16 days). 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 and MD Patient parts with a 3:1 ratio (36 active, 12 placebo).

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, 4, 7,10, 13 and 16.

Eligibility criteria: Inclusion Criteria:

(Healthy Participants (SAD and MAD cohorts)):

* Healthy adult males and females, 18 to 55 years of age (inclusive) at the time of screening.
* 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):

* 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).
* 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.
* 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.

Exclusion Criteria:

(Healthy Participants (SAD and MAD cohorts)):

* History or presence of significant cardiovascular, pulmonary, hepatic, renal, haematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease as deemed by the Principal Investigator.
* History of myocardial infarction (MI), transient ischemic attack (TIA), stroke, or familial history of coronary artery disease or first-degree heart attack below the age of 60.
* Any clinically significant ECG abnormality at Screening
* Diabetic participants

(Patients (MD cohort):

* Percutaneous coronary intervention or diagnostic angiogram planned after screening.
* Documented episode of post-MI pericarditis in the 3 months before enrollment.
* Ongoing heart failure as defined by Class IV New York Heart Association
* History or presence of significant pulmonary, hepatic, renal, haematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease.
* Ongoing infection or febrile illness.
* Ongoing atrial fibrillation or flutter.
* History of MI, TIA, or stroke diagnosed within the 12 months prior to screening.
* History of or planned coronary artery bypass grafting.
* Any cardiac intervention or cardiac hospitalization in the past 12 months
* Any clinically significant ECG abnormality at Screening.
* Participants with contraindications to CTA.

Primary outcomes:
measure: Safety outcome measures (Adverse Events)
timeFrame: From enrolment through 4 weeks for SAD Participants, 6 weeks for MAD Participants and 28 weeks for MD Patients
measure: Safety outcome measures (Vital Signs: Systolic Blood Pressure)
timeFrame: From enrolment through 4 weeks for SAD Participants, 6 weeks for MAD Participants and 28 weeks for MD Patients
measure: Safety outcome measures (Vital Signs: Diastolic Blood Pressure)
timeFrame: From enrolment through 4 weeks for SAD Participants, 6 weeks for MAD Participants and 28 weeks for MD Patients
measure: Safety outcome measures (Vital signs: Heart Rate)
timeFrame: From enrolment through 4 weeks for SAD Participants, 6 weeks for MAD Participants and 28 weeks for MD Patients
measure: Safety outcome measures (Vital signs: Respiratory Rate)
timeFrame: From enrolment through 4 weeks for SAD Participants, 6 weeks for MAD Participants and 28 weeks for MD Patients
measure: Safety outcome measures (Vital signs: Temperature)
timeFrame: From enrolment through 4 weeks for SAD Participants, 6 weeks for MAD Participants and 28 weeks for MD Patients
measure: Safety outcome measures (Clinical Laboratory Parameters)
timeFrame: From enrolment through 4 weeks for SAD Participants, 6 weeks for MAD Participants and 28 weeks for MD Patients
measure: Safety outcome measures (ECG QTCF Interval)
timeFrame: From enrolment through 4 weeks for SAD Participants, 6 weeks for MAD Participants and 28 weeks for MD Patients
measure: Safety outcome measures (Injection site reactions)
timeFrame: 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
measure: Safety outcome measures (Audiometry: PTA)
timeFrame: From enrolment through 24 hours post dose for SAD Participants (Day 2), 24 hours post dose for MAD and MD Patients Participants (Day 17),
measure: Safety outcome measures (Audiometry: HFA)
timeFrame: From enrolment through 24 hours post dose for SAD Participants (Day 2), 24 hours post dose for MAD and MD Patients Participants (Day 17),
measure: Safety outcome measures (Audiometry: Self-evaluation questionnaire (THI))
timeFrame: From enrolment through 24 hours post dose for SAD Participants (Day 2), 24 hours post dose for MAD and MD Patients Participants (Day 17),
measure: Safety outcome measures (Audiometry: Self-evaluation questionnaire (DHI))
timeFrame: 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 outcomes:
measure: Pharmacokinetics Outcome Measures (Cmax)
timeFrame: Day 1 for the SAD and Days 1 and 16 for the multiple dosing parts
measure: Pharmacokinetics Outcome Measures (Tmax)
timeFrame: Day 1 for the SAD and Days 1 and 16 for the multiple dosing parts
measure: Pharmacokinetics Outcome Measures (half-life (t1/2))
timeFrame: Day 1 for the SAD and Days 1 and 16 for the multiple dosing parts
measure: Pharmacokinetics Outcome Measures (AUC0-t and AUC0-inf)
timeFrame: Day 1 for the SAD and Days 1 and 16 for the multiple dosing parts
measure: Pharmacokinetics Outcome Measures (Total Plasma Clearance (CL))
timeFrame: Day 1 for the SAD and Days 1 and 16 for the multiple dosing parts
measure: Pharmacokinetics Outcome Measures (Volume of Distribution (Vd))
timeFrame: Day 1 for the SAD and Days 1 and 16 for the multiple dosing parts
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: CMAX Clinical Research
state: South Australia
Study officials:
References: