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Trial registered on ANZCTR


Registration number
ACTRN12624000891527
Ethics application status
Approved
Date submitted
26/06/2024
Date registered
22/07/2024
Date last updated
17/11/2024
Date data sharing statement initially provided
22/07/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
A Randomized, Double-Blind, Placebo-Controlled, Phase 1, Dose Escalation (with optional food effect) Study of Orally Administered TRX-100 to Evaluate the Safety, Tolerability and Pharmacokinetics of Single Ascending Doses of TRX-100 in Healthy Volunteers
Scientific title
A Randomized, Double-Blind, Placebo-Controlled, Phase 1, Dose Escalation (with optional food effect) Study of Orally Administered TRX-100 to Evaluate the Safety, Tolerability and Pharmacokinetics of Single Ascending Doses of TRX-100 in Healthy Volunteers
Secondary ID [1] 312206 0
TRX-100-0001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Influenza 333881 0
Condition category
Condition code
Respiratory 330558 330558 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a double-blind, randomised, placebo-controlled study evaluating the safety, tolerability, and pharmacokinetics (PK) of TRX-100 (and its major active metabolite TRX-101). A total of up to 32 healthy volunteers are planned to be enrolled in 4 cohorts (8 participants per cohort). Eligible participants in each cohort will be randomised to receive a single administration of TRX-100 or placebo under fasted conditions.

Dose escalation will be conducted sequentially starting with Cohort 1. The dose levels to be evaluated will be 80 mg, 120 mg, 240 mg and 480 mg. Sentinel dosing will be utilised in all four cohorts. Dosing in a cohort at all dose levels will commence with 2 sentinel participants with 1 of the 2 sentinels randomized to receive TRX-100 and the other randomized to receive placebo.

Participants in Cohorts 1, 2, 3 and 4 will receive a single oral dose of TRX-100 or placebo capsules administered on Day 1.

The decision to escalate between dose levels will be based on review of the Day 6 safety and available PK data by the study Safety Review Committee (SRC).

A further 8 participants may be enrolled in an additional optional cohort (Cohort 5) to determine the potential effect of food on the PK of TRX-100 and TRX-101. The optional food effect cohort (Cohort 5) will involve 2 dose administrations at 2 study periods separated by a 28-day washout. The inclusion of the additional (optional) cohort to investigate the potential effect of food on the PK of TRX-100 and TRX-101 will be determined by the SRC following review of the safety and PK data obtained from Cohorts 1, 2, 3 and 4. The dose for Cohort 5 (Food Effect) is planned to be 120 mg but will be confirmed following a Safety Review Committee (SRC) meeting upon completion of Cohorts 1, 2, 3 and 4. A total of 8 participants will be enrolled into this cohort with 6 to receive the active study drug and two (2) to receive the placebo.

Adherence to the study intervention will be done via supervised drug administration.
Intervention code [1] 328654 0
Treatment: Drugs
Comparator / control treatment
Placebo – Capsules containing microcrystalline cellulose and identical in appearance to the study intervention will be used in this study.
Control group
Placebo

Outcomes
Primary outcome [1] 338476 0
To assess the safety and tolerability of a single oral administration of TRX-100 administered at different dose levels in healthy adult volunteers.
Timepoint [1] 338476 0
- Adverse events (AEs)/serious AEs (SAEs) are reviewed daily from Day -1 until Day 28 (End of Study/Early Termination Visit [EOS/ETV}). Possible AEs could be hyperglycaemia (high blood sugar), rash, wheezing, sweating or accelerating heartbeat.
- Body Weight -assessed at Screening, Day -1 and Day 28 (End of Study/Early Termination visit [EOS/ETV]).
- Vital signs - Assessed at Screening, Day -1, pre-dose Day 1 - 1, 2, 3, 4, 6, 8, 12 hrs post-dose, Day 2 24, 36 hrs post-dose, Day 3 48 hrs post-dose, Day 4 72 hrs post-dose, Day 6 post-dose, Day 8 post-dose, Day 12 post-dose, Day 16 post-dose and Day 28 post-dose (End of Study/Early Termination Visit [EOS/ETV}).
- Electrocardiogram (ECG) - 12-lead ECG recordings will be obtained in triplicate at screening only, then single recordings obtained at Screening, Day -1, pre-dose Day 1 2 and 6 hrs post-dose, Day 2 24 hrs post-dose, Day 4 72 hrs post-dose, Day 6 post-dose, Day 8 post-dose, Day 12 post-dose, Day 16 post-dose and Day 28 post-dose (End of Study/Early Termination Visit [EOS/ETV}).
- Clinical laboratory evaluations - blood and urine samples will be collected from Screening, Day -1, Day 1 6hrs post-dose, Day 2 24 hrs post-dose, Day 4 72 hrs post-dose, Day 6 post-dose, Day 8 post-dose, Day 12 post-dose, Day 16 post-dose and Day 28 hrs post-dose (End of Study/Early Termination Visit [EOS/ETV}).
Secondary outcome [1] 436076 0
To measure the PK of TRX-100 and its active metabolite TRX-101 in plasma following a single oral administration of TRX-100 at different dose levels in healthy adult volunteers.
Timepoint [1] 436076 0
Blood plasma samples will be collected pre-dose Day 1, then 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-dose, Day 2 24 and 36 hrs post-dose, Day 3 48 hrs post-dose, Day 4 72 hrs post-dose, Day 6, 8, 12, and Day 16 post-dose and Day 28 post-dose (End of Study/Early Termination Visit [EOS/ETV}).
Secondary outcome [2] 436310 0
Exploratory Outcome: To evaluate TRX100/TRX101 target engagement.
Timepoint [2] 436310 0
Blood plasma samples will be collected pre-dose Day 1, then 6 hrs post-dose, Day 2 24 hrs post-dose, Day 3 48 hrs post-dose, Day 4 72 hrs post-dose, Day 6 post-dose Day 16 post-dose and Day 28 post-dose (End of Study/Early Termination Visit [EOS/ETV}).
Secondary outcome [3] 436311 0
Exploratory Outcome: To assess the effect of food on the PK of TRX-100 and its active metabolite TRX-101 in plasma following a single oral administration of TRX-100 under fasted and fed conditions.
Timepoint [3] 436311 0
Blood plasma samples will be collected for Period 1 pre-dose Day 1, then 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-dose, Day 2 24 and 36 hrs post-dose, Day 3 48 hrs post-dose, Day 4 72 hrs post-dose, Day 6, 8, 12 and Day 16 post-dose. Blood plasma samples will be collected for Period 2 pre-dose Day 28, then 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-dose, Day 29 24 and 36 hrs post-dose, Day 30 48 hrs post-dose, Day 31 72 hrs post-dose, Day 33, 35, 39, 43 post-dose and Day 55 post-dose (End of Study/Early Termination Visit [EOS/ETV}).

Eligibility
Key inclusion criteria
1. Must have given written informed consent before any study-related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects.
2. Adult males and females, 18 to 64 years of age (inclusive) at screening.
3. Body mass index (BMI) greater than or equal to 18.5 and less than or equal to 32.0 kg/m2, with a body weight (to 1 decimal place) greater than or equal to 50.0 kg at screening.
4. Medically healthy without clinically significant abnormalities (in the opinion of the Investigator) at the screening visit and prior to dosing at the timepoints indicated in the Schedule of Assessments, including:
a. Physical examination without any clinically significant findings in the opinion of the Investigator.
b. Systolic blood pressure in the range of 90 mm Hg to 149 mm Hg; diastolic blood pressure in the range of 50 mm Hg to 90 mm Hg after 5 minutes in a supine or semi-supine position
c. Heart rate (HR) in the range of 40 to 100 bpm
d. Body temperature (tympanic or oral) in the range 35.5°C to 37.5°C (inclusive).
e. No clinically significant findings in serum chemistry, haematology, coagulation and urinalysis tests as judged by the Investigator.
f. Triplicate 12-lead ECG (taken after the volunteer has been supine or semi-supine for at least 5 minutes) with a QTcF less than or equal to 450 msec for males and less than or equal to 470 msec for females and no clinically significant abnormalities.
g. Haemoglobin A1C (HbA1c) levels within the local laboratory standard reference range.
5. Be willing to not smoke (including tobacco, nicotine replacement therapy, e-cigarettes) from 7 days prior to dose administration on Day 1 to Day 12 (inclusive) for all cohorts. For optional Cohort 5 only, participants must also be willing to not smoke (including tobacco, nicotine replacement therapy, e-cigarettes) from 7 days prior to dose administration on Day 28 to Day 39 (inclusive) .
6. Female volunteers must:
a. Be of nonchildbearing potential i.e., surgically sterilized (hysterectomy, bilateral salpingectomy, bilateral oophorectomy at least 6 weeks before screening) or postmenopausal (where postmenopausal is defined as no menses for 12 months without an alternative medical cause, and if under the age of 55 years a follicle-stimulating hormone (FSH) level >40 IU/L at the screening visit), or
b. If of childbearing potential, must agree not to donate ova, not to attempt to become pregnant and, if engaging in sexual intercourse with a male partner, must agree to use an acceptable method of contraception from signing the consent form until at least 30 days after the last dose of the study drug.
7. Male volunteers, if not surgically sterilized, must agree to:
a. Not donate sperm after signing consent, during the study, and at least 90 days after the EoS visit.
b. If engaging in sexual intercourse with a female partner who could become pregnant, must agree to use an acceptable method of contraception from signing the consent form until at least 90 days after the last dose of study drug.
8. Have suitable venous access for blood sampling.
9. Be willing and able to comply with all study assessments and adhere to the protocol schedule and restrictions.
Minimum age
18 Years
Maximum age
64 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic or neurological disease, including any acute illness or major surgery within the past 3 months determined by the PI to be clinically significant.
2. Acute infections within 4 weeks prior to screening or current infection that requires systemically absorbed antibiotic, antifungal, antiparasitic or antiviral medications.
3. Presence or history of any abnormality or illness, including gastrointestinal surgery, which in the opinion of the PI may affect absorption, distribution, metabolism or elimination of the study drug.
4. Any history of malignant disease in the last 5 years (excludes surgically resected skin squamous cell or basal cell carcinoma).
5. Any screening laboratory result outside the normal laboratory reference range (as confirmed upon repeated testing) and deemed clinically significant by the PI.
6. Presence of clinically relevant immunosuppression from, but not limited to, immunodeficiency conditions such as common variable hypogammaglobulinemia.
7. Use of or plans to use systemic immunosuppressive (e.g., corticosteroids by any route, methotrexate, azathioprine, cyclosporine) or immunomodulating medications (e.g., interferon) during the study or within 5 half-lives of individual agent or within 28 days (whichever is longer) prior to Screening.
8. Use of or plans to use agents (e.g., grapefruit and grapefruit products) that have clinically significant interaction with CYP3A4 or the use of any medications that could have a significantly impact on organ function (e.g., barbiturates, omeprazole, cimetidine) during the study or within 5 half-lives of individual agent or within 7 days (whichever is longer) prior to dosing.
9. History of risk factors for torsade de pointes (including a family history of long QT syndrome or sudden cardiac death) or clinically significant arrythmia.
10. Participant is planning to have surgery between Screening and the EoS visit.
11. Positive test results for active human immunodeficiency virus (HIV-1 or HIV-2), hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies at the screening visit.
12. Presence or having sequelae of gastrointestinal, liver, kidney, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs.
13. Estimated creatinine clearance < 60 mL/min using the Cockcroft-Gault formula.
14. Creatine kinase >2.0 x ULN at Day -1.
15. History of any drug or alcohol abuse in the past 2 years defined as >21 units of alcohol per week for males and >14 units of alcohol per week for females. Where 1 unit = 360 mL of beer, 150 mL wine, or 30 mL of spirits.
16. History of alcohol consumption in the 48 hrs prior to dosing.
17. Positive drugs of abuse, or alcohol breath test results at the screening visit or at check-in (Day -1).
18. Use of any prescription medications within 14 days or at least 5 half-lives of the medication (whichever is longer) prior to the first study drug administration, including use of any over-the-counter medication (including herbal products, nutritional, diet aids, vitamin supplements, minerals) within 7 days or at least 5 half-lives of the medication (whichever is longer) prior to the first study drug administration, with the exception of the occasional use of paracetamol (doses of 500 mg up to every 6 hours or 2 g per day maximum for no more than 3 consecutive days) or ibuprofen (doses of 400 mg up to every 6 hours or 1.2 g per day maximum for no more than 3 consecutive days), topical ointments, and vitamins or dietary supplements and medications used to manage AEs..
19. Demonstrated clinically significant (required intervention, e.g., emergency room visit, epinephrine administration) allergic reactions (e.g., food, drug, or atopic reactions, asthmatic episodes) which, in the opinion of the Investigator, would interfere with the volunteer’s ability to participate in the trial.
20. Known hypersensitivity to any of the study drug ingredients.
21. Use of any inactivated vaccinations within 14 days, or any live vaccinations within 30
days prior to the first study drug administration. Note: Participants vaccinated for COVID-19 or influenza within at least 2 weeks prior to enrollment or earlier will be considered eligible for enrollment as long as they do not present with post-vaccination clinical symptoms, have a negative rapid antigen test (in the case of COVID-19), and are deemed otherwise healthy. 22. For women of childbearing potential, a positive serum pregnancy test at the screening visit or a positive urine pregnancy test (with confirmatory serum pregnancy test) at check-in (Day -1).
23. Females who are breastfeeding or planning to breast feed at any time during the study.
24. Donation of blood or plasma within 30 days prior to first study drug administration, or loss of whole blood of more than 500 mL within 30 days prior to first study drug administration, or receipt of a blood transfusion within 1 year of first study drug administration.
25. Receiving an investigational drug in another clinical trial within 30 days or 5 half-lives of the investigational agent (whichever is longer) prior to the first study drug administration.
26. Any other condition or prior therapy that in the opinion of the Investigators would make the volunteer unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likelihood of noncompliance with any study requirements.
27. Any history of long COVID infection (defined by continuation or development of new symptoms 3 months after the initial SARS-CoV-2 infection, with these symptoms lasting for at least 2 months with no other explanation).
28. Any history of severe influenza, defined as a confirmed diagnosis of influenza resulting in hospitalization, or symptoms severe enough to disrupt daily activities for more than 7 consecutive days.

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)
All study participants who sign an informed consent form (ICF) at screening will receive a unique sequential number (i.e., a Screening Number).
Participants who meet the study eligibility criteria will be assigned a randomization number pre-dose, which corresponds to a study treatment (TRX-100 or placebo). The randomization schedule will be prepared by an unblinded statistician and maintained under controlled access. A copy of the randomization schedule (enclosed in a code break envelop) will be sent to the clinical site by the unblinded statistician and will be stored at the site in a secure, restricted access area.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The allocation to TRX-100 or placebo will be performed using a block randomization algorithm and will be documented in the study randomization schedule.
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
31/07/2024
Actual
13/08/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
40
Accrual to date
24
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 26665 0
Scientia Clinical Research - Randwick
Recruitment postcode(s) [1] 42704 0
2031 - Randwick

Funding & Sponsors
Funding source category [1] 316582 0
Commercial sector/Industry
Name [1] 316582 0
Trawsfynydd Therapeutics AU Pty Ltd (on behalf of Traws Pharma, Inc.)
Country [1] 316582 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Trawsfynydd Therapeutics AU Pty Ltd (on behalf of Traws Pharma, Inc.)
Address
Country
Australia
Secondary sponsor category [1] 318762 0
Commercial sector/Industry
Name [1] 318762 0
Avance Clinical Pty Ltd
Address [1] 318762 0
Country [1] 318762 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 315370 0
Bellberry Human Research Ethics Committee C
Ethics committee address [1] 315370 0
Ethics committee country [1] 315370 0
Australia
Date submitted for ethics approval [1] 315370 0
12/06/2024
Approval date [1] 315370 0
11/07/2024
Ethics approval number [1] 315370 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 134486 0
Dr Christopher Argent
Address 134486 0
Scientia Clinical Research Ltd, The Bright Building, Level 5, Corner High & Avoca Streets, Randwick NSW2031, Australia
Country 134486 0
Australia
Phone 134486 0
+61 2 9382 5844
Fax 134486 0
Email 134486 0
christopher.argent@scientiaclinicalresearch.com.au
Contact person for public queries
Name 134487 0
Christopher Argent
Address 134487 0
Scientia Clinical Research Ltd, The Bright Building, Level 5, Corner High & Avoca Streets, Randwick NSW2031, Australia
Country 134487 0
Australia
Phone 134487 0
+61 2 9382 5844
Fax 134487 0
Email 134487 0
christopher.argent@scientiaclinicalresearch.com.au
Contact person for scientific queries
Name 134488 0
Christopher Argent
Address 134488 0
Scientia Clinical Research Ltd, The Bright Building, Level 5, Corner High & Avoca Streets, Randwick NSW2031, Australia
Country 134488 0
Australia
Phone 134488 0
+61 2 9382 5844
Fax 134488 0
Email 134488 0
christopher.argent@scientiaclinicalresearch.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.