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

Official title

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

Overview

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.

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.

Interventions

• 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.
• Other Placebo
  Placebo will be provided as a sterile clear, colourless solution formulated to match viscosity of the UDP-003 solution.

Primary outcome measures

• Safety outcome measures (Adverse Events) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: 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: PTA) [Time frame: 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 (6)

• Pharmacokinetics Outcome Measures (Cmax) [Time frame: Day 1 for the SAD and Days 1 and 16 for the multiple dosing parts]
• Pharmacokinetics Outcome Measures (Tmax) [Time frame: Day 1 for the SAD and Days 1 and 16 for the multiple dosing parts]
• Pharmacokinetics Outcome Measures (half-life (t1/2)) [Time frame: Day 1 for the SAD and Days 1 and 16 for the multiple dosing parts]
• Pharmacokinetics Outcome Measures (AUC0-t and AUC0-inf) [Time frame: Day 1 for the SAD and Days 1 and 16 for the multiple dosing parts]
• Pharmacokinetics Outcome Measures (Total Plasma Clearance (CL)) [Time frame: Day 1 for the SAD and Days 1 and 16 for the multiple dosing parts]
• Pharmacokinetics Outcome Measures (Volume of Distribution (Vd)) [Time frame: Day 1 for the SAD and Days 1 and 16 for the multiple dosing parts]

Eligibility criteria

Inclusion criteria

All Participants:

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

Healthy Participants (SAD and MAD cohorts):

• Healthy adult males and females, 18 to 65 years of age (inclusive) at the time of screening.
• Adult males and females of body mass index (BMI) ≥ 18 and ≤ 32 kg/m² and body weight ≥ 50 and ≤ 120 kg.
• 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).
• 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).
• Adult males and females of body mass index (BMI) ≥ 18
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Australia · 1 center

• CMAX Clinical Research — Adelaide

Identifiers

NCT: NCT06813339 · CTx-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗