Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001349730
Ethics application status
Approved
Date submitted
14/10/2022
Date registered
20/10/2022
Date last updated
10/12/2023
Date data sharing statement initially provided
20/10/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 1 Study of Usynova Pharmaceuticals UA021 in healthy participants for the evaluation of safety, tolerability, and drug concentration in progressively increasing single and multiple daily dose levels
Scientific title
A Phase 1, Randomized, Double-blind, Placebo-controlled, Single- and Multiple-Ascending Dose Study to Investigate the Safety, Tolerability, and Pharmacokinetics of UA021 in Healthy Participants
Secondary ID [1] 308172 0
Usynova Pharmaceuticals Study UA021-AU001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Psoriasis 327893 0
Condition category
Condition code
Inflammatory and Immune System 324982 324982 0 0
Autoimmune diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
UA021-AU001 is a two-part study within which parts 1 and 2 will be conducted sequentially. Each study part and stage will involve unique participants.
Part A: Single ascending dose cohorts
Part A evaluates the single-dose administration of UA021 or matched placebo (a capsule that looks the same as the study drug but has no active substances): 5mg, 15mg, 30mg, 60mg, and 120mg respectively in cohorts 1-5. Each cohort will consist of 8 participants who will each receive a single dose of investigational drug or matched placebo under fasted state (after an overnight fast of at least 8 hours prior to dosing), Healthy volunteers will stay in the clinical research unit for the entire duration of dosing and will take study drug under direct supervision of the clinical research unit staff.
Each of the SAD cohorts will be observed for at least 14 days. Safety, tolerability, and available PK data will be reviewed by the SRC for dose escalation and the actual doses to be administered may be adjusted accordingly.
Part B: Multiple ascending dose cohorts
Each cohort will consist of 8 participants who will each receive UA021 or matched placebo (a capsule that looks the same as the study drug but has no active substances): 15mg, 30mg, and 60mg given by oral administration twice daily for 14 days. after an overnight fast of at least 8 hours prior to morning dosing and, a 1 hour fast prior to the evening dose. Healthy volunteers will stay in the clinical research unit for the entire duration of dosing and will take study drug under direct supervision of the clinical research unit staff.
The actual starting dose including dose regimen for Part B and conditions for the administration of the study intervention will determined by SRC after reviewing of the safety, tolerability, and available PK data of Part A. Part B may be initiated prior to or after the completion of Part A at the discretion of the SRC. In Part B, after an observation period of at least 28 days (from the first day of dosing) and review of the safety, tolerability, and available PK data of all participants enrolled in the previous cohorts, the next actual dose cohort may be adjusted by the SRC. These dose adjustments may involve either an increase or a decrease in the planned dose or a change in the dosing frequency.
Intervention code [1] 324621 0
Treatment: Drugs
Comparator / control treatment
Matching placebo: The placebo capsules are a gelatine capsule shell containing white to off-white powder, consisting of the excipient’s microcrystalline cellulose, lactose monohydrate, croscarmellose sodium and magnesium stearate. The capsules have the exact same composition as the active drug product minus the active ingredient
Control group
Placebo

Outcomes
Primary outcome [1] 332779 0
Integrated safety evaluation. The safety parameters to be assessed include AEs/SAEs, and changes in clinical laboratory tests, vital signs, 12-lead ECG, and physical examinations from baseline.
Adverse events will be reported by the participant. The Investigator and any designees are responsible for detecting, documenting, and recording events that meet the definition of an AE or SAE. Events meeting the AE definition include:
• Any abnormal laboratory test results (hematology, coagulation, clinical chemistry, or urinalysis) or other safety assessments (eg, ECG, vital signs measurements, or physical examinations), including those that worsen from baseline, considered clinically significant in the medical and scientific judgment of the Investigator.
• Exacerbation of a chronic or intermittent pre-existing condition including either an increase in frequency and/or intensity of the condition.
• New conditions detected or diagnosed after study drug administration although it may have been present before the start of the study.
• Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.
• Signs, symptoms, or the clinical sequelae of a suspected overdose of either study drug or a concomitant medication. Overdose per se will not be reported as an AE/SAE unless it is an intentional overdose taken with possible suicidal/self-harming intent. Such overdoses should be reported regardless of sequelae.

Severity categories of AE assessment include mild, moderate, and severe, as defined below-
• Mild: Asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated
• Moderate: Minimal, local, or non-invasive intervention indicated, limiting age-appropriate instrumental activities of daily living.
• Severe: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living
• Life threatening: Life-threatening consequences: urgent intervention indicated.
• Death: Death related to AE

Vital signs measurements will include tympanic body temperature, pulse rate, and blood pressure. Blood pressure and pulse rate will be assessed with a completely automated device; manual techniques will be used only if an automated device is not available.
Timepoint [1] 332779 0
Part A: Single Ascending Dose: Day -1 (the day before dosing) to Day 14 (13 days post-dose)
Clinical laboratory blood tests will be assessed at Screening and on Day -1, Day 1, Day 3, Day 3, and Day 14.
Clinical laboratory urinalysis will be assessed at Screening and on Day -1, Day 1, Day 7, and Day 14.
A complete physical examinations will be assessed at screening
Vital signs will be assessed at Screening and on Day -1, Day 1, Day 2, Day 3, Day 7, and Day 14.
12-Lead ECG will be assessed Screening and on Day -1, Day 1, Day 3, and Day 14.
AEs/SAEs will be assessed at all timepoints.

Part B: Multiple Ascending Dose: Day -1 (the day before dosing) to Day 28 (14 days post last dose)
Clinical laboratory blood tests will be assessed at Screening and on Day -1, Day 1, Day 7, and Day 14.
Clinical laboratory urinalysis will be assessed at Screening and on Day -1, Day 1, Day 7, and Day 14.
A complete physical examination will be assessed at screening.
Vital signs will be assessed at Screening and on Day -1, Day 1, Day 7, Day 14, Day 15, Day 16, and Day 28.
12-Lead ECG will be assessed Screening and on Day -1, Day 1, Day 7, Day 14, Day 15, Day 16, and Day 28.
AEs/SAEs will be assessed at all timepoints.
Secondary outcome [1] 414699 0
Pharmacokinetic profile
• Part A (SAD): Tmax, Cmax, AUC0-t, AUC0 inf, t1/2, CL/F, Vz/F, lambda z, percentage AUCex, Ae, fe, CLR, and Rac
• Part B (MAD): Tmax, Cmax, AUC0-t, AUC0 inf, t1/2, CL/F, Vz/F, lambda z, percentage AUCex, Ae, fe, CLR, and Rac
Timepoint [1] 414699 0
• Part A (SAD): blood samples collected at: pre-dose and at and at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8,12, 24, and 48-hours post-dose.
• Part B (MAD): blood samples collected on Day 1 pre-dose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 24 hours post the D1 morning dose. On Day 3, Day 5, Day 7, Day 9, Day 11, and Day 13, plasma samples will be collected pre-dose and on Day 14 plasma samples will be collected pre-dose and at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10,12,24 and 48 hours after the D14 morning dose.
Secondary outcome [2] 414700 0
Pharmacodynamic profile
Relative mRNA level of IL-17A
Timepoint [2] 414700 0
• Part B (MAD): blood samples collected on Day 1 pre-dose for the morning dose and 1 hour after the evening dose on Day 1, Day 7, and Day 15.

Eligibility
Key inclusion criteria
• Must be capable of giving a signed informed consent
• Participants in good health based on medical history, physical examinations, vital
signs, 12-lead ECGs, clinical laboratory tests as determined by the Investigator.
• Body mass index (BMI) within the range of 18~32 kg/m2 (inclusive) with a minimum
body weight of 45 kg at the screening visit.
• Adhere to effective double barrier contraception or are proven post-menopausal
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
• A history of stomach or intestinal surgery or resection that would potentially alter
the absorption and/or excretion of orally administered drugs taken.
• Presence of a malabsorption syndrome e.g., Crohn’s Disease
• Any clinically significant abnormalities in laboratory test results deemed clinically
significant by the Investigator.
• History of immunological disorders, auto-immune disorders, acquired or congenital
immune deficiency or acute infection within 3 months before the start of the screening
visit.
• Active or prior hepatitis B infection or positive test for HIV or Hepatitis C
• Poorly controlled hypertension or diabetes mellitus
• Major surgery within 6 months of study entry.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Parallel
Other design features
Randomised double-blind placebo-controlled design for single and multiple ascending dose stages
Phase
Phase 1
Type of endpoint/s
Pharmacokinetics / pharmacodynamics
Statistical methods / analysis
Listings and tabulations of safety and tolerability variables
Pharmacokinetic analysis and modelling to estimate and visualise standard parameters
Sample size is based on customary practice in Phase 1 clinical studies

Recruitment
Recruitment status
Suspended
Date of first participant enrolment
Anticipated
1/12/2022
Actual
19/12/2022
Date of last participant enrolment
Anticipated
17/06/2024
Actual
24/05/2023
Date of last data collection
Anticipated
7/08/2024
Actual
Sample size
Target
64
Accrual to date
8
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 23365 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 38746 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 312429 0
Commercial sector/Industry
Name [1] 312429 0
Usynova Pharmaceuticals Australia Pty Ltd
Country [1] 312429 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
George Clinical Pty Ltd
Address
Level 5, 1 King Street
Newtown, NSW 2042
Country
Australia
Secondary sponsor category [1] 314005 0
None
Name [1] 314005 0
Address [1] 314005 0
Country [1] 314005 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311776 0
Alfred Health Ethics Committee
Ethics committee address [1] 311776 0
55 Commercial Rd,
Melbourne VIC 3004
Ethics committee country [1] 311776 0
Australia
Date submitted for ethics approval [1] 311776 0
26/10/2022
Approval date [1] 311776 0
25/11/2022
Ethics approval number [1] 311776 0

Summary
Brief summary
A first time in human study to evaluate safety, tolerability, and pharmacokinetics of UA021 capsules compared with placebo in normal healthy adult participants.
A single and multiple-ascending dose study to determine the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of UA021 in healthy adult participants. Results of this study will inform dose selection and design of studies to assess the efficacy and safety of UA021 in inflammatory diseases, including psoriasis.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 122322 0
Dr Sam Francis
Address 122322 0
Nucleus Network Pty Ltd
Level 5, Burnet Tower,
89 Commercial Rd, Melbourne 3004, Victoria
Country 122322 0
Australia
Phone 122322 0
+61458889101
Fax 122322 0
Email 122322 0
s.francis@nucleusnetwork.com.au
Contact person for public queries
Name 122323 0
Dr Sam Francis
Address 122323 0
Nucleus Network Pty Ltd
Level 5, Burnet Tower,
89 Commercial Rd, Melbourne 3004, Victoria
Country 122323 0
Australia
Phone 122323 0
+61 1800 243 733
Fax 122323 0
Email 122323 0
melbourne@nucleusnetwork.com
Contact person for scientific queries
Name 122324 0
Dr Sam Francis
Address 122324 0
Nucleus Network Pty Ltd
Level 5, Burnet Tower,
89 Commercial Rd, Melbourne 3004, Victoria
Country 122324 0
Australia
Phone 122324 0
+61 1800 243 733
Fax 122324 0
Email 122324 0
melbourne@nucleusnetwork.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
No individual data will be released in any form


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.