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Trial registered on ANZCTR


Registration number
ACTRN12623001054606
Ethics application status
Approved
Date submitted
28/07/2023
Date registered
29/09/2023
Date last updated
30/10/2023
Date data sharing statement initially provided
29/09/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
To evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of TX000045 (single ascending dose) in Healthy Volunteers
Scientific title
A double-blind, randomized, placebo-controlled, single ascending dose study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of TX000045 in healthy participants
Secondary ID [1] 310185 0
TX000045-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cardiovascular 330809 0
Condition category
Condition code
Cardiovascular 327640 327640 0 0
Other cardiovascular diseases
Respiratory 328162 328162 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
TX000045 is a biologic Fc-fusion relaxin therapeutic.

Investigational product : TX000045 or Matching placebo

Approximately 48 participants will be enrolled in this study.

Single ascending dose of TX000045 or Matching placebo will be administered to study participants via Intravenous infusion (IV) or subcutaneous (SC) injection in the proposed doses as mentioned below by the site staff. 6 participants will receive TX000045 and 2 participants will receive placebo. The infusion will be between 30 to 60 minutes.
• Cohort A: 0.3 mg/kg IV of TX000045 or matching placebo
• Cohort B: 1 mg/kg IV of TX000045 or matching placebo
• Cohort C: 300 mg SC of TX000045 or matching placebo; Cohort C may be dosed concurrently with Cohort B
• Cohort D: 3 mg/kg IV of TX000045 or matching placebo
• Cohort E: 600 mg SC of TX000045 or matching placebo; Cohort E may
be dosed concurrently with Cohort D
• Cohort F: 10 mg/kg IV of TX000045 or matching placebo
Adherence to the intervention will be monitored by study staff, CRO staff and Sponsor Staff.
Intervention code [1] 326585 0
Treatment: Drugs
Comparator / control treatment
Placebo: Buffer identical to TX000045 active without addition of TX000045.

Control group
Placebo

Outcomes
Primary outcome [1] 335454 0
To evaluate the safety and tolerability of TX000045 after single ascending doses

To be assessed by monitoring
Incidence of adverse events (AEs) and serious adverse events (SAEs): Adverse events will be assessed by clinical examination, review of patient data and self-reporting. Adverse events will be collected via verbal interview by clinic staff during the study period either in person during confinement or clinic visits or via telephone during remote contacts

Changes in clinical laboratory safety parameters including blood test results for Hematology, Serum Chemistry, Coagulation Studies.

Changes in vital signs measurements. Vital signs will include measurements of resting heart rate, systolic and diastolic blood pressure (BP) using standard manual or electronic clinical procedures.

Changes in electrocardiogram (ECG) findings

These procedures are completed using standard nursing practices or in the case of the ECG, the instructions provided by the manufacturer. These individual data are utilized to determine safety by physician assessment. Additionally, the totality of the data presented will also be factored into the determination of safety
Timepoint [1] 335454 0
Adverse Events (AEs) and Serious Adverse events (SAEs) : At Screening, Day -1, Day 1, Day 2, Day 3, Day 6, Day 8, Day 15, Day 29, Day 43, Day 57 post dose administration

Safety Laboratory assessments: At Screening, Day -1, Day 1, Day 2, Day 8, Day 15, Day 29, Day 43, Day 57 post dose administration

ECG: At Screening, Day -1, Day 1 and Day 2 post dose administration

Vital Signs: At Screening, Day -1, Day 1, Day 2, Day 3, Day 6, Day 8, Day 15, Day 29, Day 43, Day 57 post dose administration
Secondary outcome [1] 424707 0
Characterize the pharmacokinetic (PK) profile of TX000045 in healthy participants after single ascending doses of TX000045.

Standard PK parameters will be described: Cmax, Tmax, AUC last (AUC from 0 to the last measurable concentration), AUCinf (AUC from 0 to infinity), t1/2, CL (clearance), and Vz (terminal phase volume of distribution).
Timepoint [1] 424707 0
Blood sampling for PK parameters will be collected Predose, End of infusion, 6 hrs, 12 hrs post dose on Day 1, 24 hrs post dose on Day 2, 48 hours post dose on Day 3, 120 hours post dose on Day 6, 168 hours post dose on Day 8, Day 15, Day 29, Day 43 and Day 57 post dose.
Secondary outcome [2] 424709 0
Evaluate the pharmacodynamic (PD) effect of single ascending doses of TX000045 in healthy participants.

Change from baseline to day 2 in the following:

Renal plasma flow (RPF), as measured by change in plasma para-aminohippurate (PAH) over time
Renal blood flow (RBF)
Filtration fraction (FF), as calculated by GFR divided by RPF
Timepoint [2] 424709 0
Blood Sampling for RPF/GFR will be collected on Days 2, 8 and 15 for IV Cohorts A, B and D and on Days 15 and 29 for IV cohort F.

Blood sampling for RPF/GFR will be collected on Days 2, 15 and 29 for SC Cohorts C and E.

Eligibility
Key inclusion criteria
Inclusion criteria:
Participants must meet the following criteria to be enrolled in this study:
• Is a male or a female of non–childbearing potential between the ages of 18 and 55 years.
• Is judged to be in good health based upon medical history, physical examination, vital signs, ECGs, and routine laboratory tests.
• Has a BMI (body mass index) between 18 and 32 kg per meter square at screening.
• Understands the study procedures and agrees to participate in the study by giving written informed consent.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Exclusion criteria
Participants are excluded from the study if any of the following criteria apply:
• Is mentally or legally incapacitated, has significant emotional problems at the time of the study, or has a history of significant psychiatric disorders at the discretion of the investigator.
• Has any clinically significant physical examination abnormalities observed during the screening visit or would not be a good candidate for participation in the study in the opinion of the investigator.
• Has clinically significant abnormal complete blood count, clinical chemistry, or urine analysis at screening or Day -1. In asymptomatic participants, any abnormal laboratory results, including creatine phosphokinase within 3 times the upper limit of normal with suspected cause due to rigorous physical activities, may be repeated once during the screening period.
• Was hospitalized for any reason within 30 days of the screening visit.
• Has any history of clinically significant renal, neurologic, gastrointestinal, hepatic, or respiratory disease. Note that subjects with fully resolved childhood asthma with no recurrence in adulthood may be enrolled.
• Has a history of anaphylaxis or other significant allergy in the opinion of the investigator.
• Has a history of clinically significant cardiovascular disease including arrhythmias, conduction abnormalities, or clinically significant abnormal vital signs.
• Was previously administered relaxin or relaxin fusion proteins.
• Was dosed in any clinical research study evaluating another investigational drug (including biologics) or therapy (including specific immunotherapy) within 90 days or less than or equal to 5 half-lives (whichever is longer) of an investigational biologic drug, or less than or equal to 4 weeks for other investigational products, before the screening visit.

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)
Subjects will be enrolled after signing the Informed Consent Form. The Contract Research Organisation will create a master randomisation schedule and code break envelopes, which will be delivered to the site's unblinded pharmacy before dosing. The active and placebo products will be infused through a line that is covered to conceal active from placebo.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A printed randomisation schedule will be generated using permuted blocked fixed method.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
10/10/2023
Actual
10/10/2023
Date of last participant enrolment
Anticipated
30/01/2024
Actual
Date of last data collection
Anticipated
25/03/2024
Actual
Sample size
Target
48
Accrual to date
56
Final
Recruitment in Australia
Recruitment state(s)
QLD

Funding & Sponsors
Funding source category [1] 314353 0
Commercial sector/Industry
Name [1] 314353 0
Tectonic Therapeutic
Country [1] 314353 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Tectonic Therapeutic
Address
490 Arsenal Way, Suite 210Watertown, MA 02472
Country
United States of America
Secondary sponsor category [1] 316304 0
None
Name [1] 316304 0
Address [1] 316304 0
Country [1] 316304 0
Other collaborator category [1] 282761 0
Commercial sector/Industry
Name [1] 282761 0
Novotech Australia Pty Limited
Address [1] 282761 0
Level 3, 235 Pyrmont Street, Pyrmont, NSW 2009
Country [1] 282761 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313448 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 313448 0
55 Commercial Road, Melbourne VIC 3004, Australia
Ethics committee country [1] 313448 0
Australia
Date submitted for ethics approval [1] 313448 0
24/07/2023
Approval date [1] 313448 0
25/08/2023
Ethics approval number [1] 313448 0

Summary
Brief summary
This double blind, placebo controlled, first-in-human (FIH) study will assess the safety, tolerability, PK, PD, and immunogenicity of TX000045 in healthy men or women of non-childbearing potential. This study will establish doses of TX000045 that are safe, well tolerated, and exhibit appropriate PD effects to warrant further clinical investigation.

Who is it for?
You may be eligible for this study if you are a healthy adult aged between 18 and 55 years old.

Approximately 48 healthy participants will be enrolled in the study.
The duration of participation in this study is approximately 3 months (inclusive of a 27-day screening window, 1-day baseline period, and a 57- day follow-up period after dosing) across 6 cohorts of 8 participants each.
Each participant will receive a single dose of TX000045 or matching placebo, randomized in a 3:1 ratio per cohort, via at least a 30-minute intravenous (IV) infusion or subcutaneous (SC) injection.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 128198 0
Dr Kristi Mclendon
Address 128198 0
Level 5 Clive Berghofer Cancer Centre Research Centre, 300 Herston Road, Herston, QLD 4006
Country 128198 0
Australia
Phone 128198 0
+61 073707 2720
Fax 128198 0
Email 128198 0
k.mclendon@nucleusnetwork.com.au
Contact person for public queries
Name 128199 0
Dr Cary Zhang
Address 128199 0
Nucleus Network Brisbane, Level 5 Clive Berghofer Cancer Centre Research Centre, 300 Herston Road, Herston, QLD 4006
Country 128199 0
Australia
Phone 128199 0
+611411317839
Fax 128199 0
Email 128199 0
c.zhang@nucleusnetwork.com.au
Contact person for scientific queries
Name 128200 0
Dr Kristi Mclendon
Address 128200 0
Level 5 Clive Berghofer Cancer Centre Research Centre, 300 Herston Road, Herston, QLD 4006
Country 128200 0
Australia
Phone 128200 0
+61 073707 2720
Fax 128200 0
Email 128200 0
k.mclendon@nucleusnetwork.com.au

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


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.