Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000220561
Ethics application status
Approved
Date submitted
5/02/2024
Date registered
6/03/2024
Date last updated
20/05/2024
Date data sharing statement initially provided
6/03/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
A Randomised, Double-Blind, Placebo-Controlled, First-in-Human Study of Orally Administered 83-0060 to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of 83-0060 in Healthy Volunteers
Scientific title
A Randomised, Double-Blind, Placebo-Controlled, First-in-Human Study of Orally Administered 83-0060 to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of 83-0060 in Healthy Volunteers
Secondary ID [1] 311447 0
83-0060-0001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
SARS-CoV-2 332738 0
Condition category
Condition code
Respiratory 329458 329458 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a single centre, Phase I, single- and multiple-dose escalation clinical trial to be conducted in healthy volunteers. This study will be subdivided into two parts:

Part A Single ascending dose (SAD): will comprise of up to 5 cohorts with one optional cohort (SAD Cohorts 1, 2, 3, 4, 5 under fasted conditions and optional SAD Cohort Xb under fed conditions). All cohorts will enrol 8 participants each with 6 participants randomised to receive 83-0060 capsules orally and 2 participants randomised to receive placebo capsules orally as a single dose on Day 1 with a dose range of 15 mg to 600 mg.

Part B Multiple ascending dose (MAD): will comprise of 2 cohorts (MAD Cohorts 1 and 2). Each cohort will enrol 8 participants each with 6 participants randomised to receive 83-0060 capsules orally and 2 participants randomised to receive placebo capsules orally once daily on Days 1 – 10 with a dose range of 50 mg - 150 mg.

The decision to commence Part B of the study will be based upon Safety Review Committee (SRC) review of blinded clinical and laboratory safety data through to and including the End of Study (EoS) visit and available blinded PK data up to day 14 post-dose of all Cohorts in Part A.

Cohorts will be dosed in an escalating order with participants only able to enrol in one dose cohort.

Adherence to the intervention will be done via supervised drug administration.
Intervention code [1] 327889 0
Treatment: Drugs
Comparator / control treatment
Placebo – oral capsules containing microcrystalline cellulose instead of investigational product will be used in this study.
Control group
Placebo

Outcomes
Primary outcome [1] 337270 0
To assess the pharmacokinetics (PK), including plasma concentrations, of 83-0060 in plasma following administration of single oral doses in healthy adult volunteers.
Timepoint [1] 337270 0
Blood plasma samples will be collected pre-dose Day 1, then 0.25, 0.5, 1, 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 and Day 8 168 hrs post-dose (End of Study/Early Termination Visit [EOS/ETV}).
Primary outcome [2] 337271 0
To assess the PK, including plasma concentrations, of 83-0060 in plasma following administration of multiple oral doses in healthy adult volunteers.
Timepoint [2] 337271 0
Blood plasma samples will be collected pre-dose Day 1, then 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12 hrs post-dose, Day 2 24 hrs post-dose, then pre-dose (within 15 mins) on Days 3 - 9, pre-dose Day 10 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12 hrs post-dose, Day 11 24 hrs post-last dose, Day 12 48 hrs post-last dose, Day 13 72 hrs post-last dose and Day 17 168 hrs post-last dose (End of Study/Early Termination Visit [EOS/ETV}).
Secondary outcome [1] 431280 0
Composite Outcome: To assess the safety and tolerability of single oral doses of 83-0060 in healthy adult volunteers.
Timepoint [1] 431280 0
Adverse events - will be graded using a three-point severity scale (mild, moderate, severe) and assessed continuously as they are reported or observed and reviewed daily from Day - 1 until Day 8 (End of Study/Early Termination visit [EOS/ETV]).

Body weight will be measured using electronic scales and assessed at Screening, Day -1 and Day 8 (End of Study/Early Termination visit [EOS/ETV]).

Vital signs - Blood pressure and heart rate is measured using sphygmomanometer, respiratory rate by manual breath count and temperature by thermometer. Assessed at Screening, Day -1, pre-dose Day 1 0.08, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-dose, Day 2 24 hrs post-dose, Day 3 48 hrs post-dose, Day 4 72 hrs post-dose and Day 8 168 hrs 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 pre-dose Day 1 1 and 6 hrs post-dose, Day 2 24 hrs post-dose, Day 4 72 hrs post-dose and Day 8 168 hrs 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 6 hrs post-dose, Day 2 24 hrs post-dose, Day 3 48 hrs post-dose and Day 8 168 hrs post-dose (End of Study/Early Termination Visit [EOS/ETV}).
Secondary outcome [2] 431281 0
Composite Outcome: To assess the safety and tolerability of multiple oral doses of 83-0060 in healthy adult volunteers
Timepoint [2] 431281 0
Adverse events - will be graded using a three-point severity scale (mild, moderate, severe) and assessed continuously as they are reported or observed and reviewed daily from Day - 1 until Day 17 (End of Study/Early Termination visit [EOS/ETV]).

Body weight will be measured using electronic scales and assessed at Screening, Day -1 and Day 17 (End of Study/Early Termination visit [EOS/ETV]).

Vital signs - Blood pressure and heart rate is measured using sphygmomanometer, respiratory rate by manual breath count and temperature by thermometer. Assessed at Screening, Day -1, pre-dose Day 1 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-dose,
Secondary outcome [3] 431282 0
To assess the effect of food on the PK of 83-0060 following administration of a single oral dose in healthy adult volunteers
Timepoint [3] 431282 0
Blood plasma samples will be collected pre-dose Day 1, then 0.25, 0.5, 1, 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 and Day 8 168 hrs 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 65 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 160 mm Hg; diastolic blood pressure in the range of 50 mm Hg to 95 mm Hg.
c. HR in the range of 45 to 100 bpm after 5 minutes in a supine position
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, including the following specific findings:
i. Haemoglobin, platelet count, WBC count, lymphocyte count, and neutrophil count within normal ranges (as per local laboratory standard ranges), WBC count (> 3.0 x 109/L), lymphocyte count (> 1.0 x 109/L), and neutrophil count (> 1.5 x 109/L)
ii. AST, ALT and total bilirubin < 1.5 x ULN (note: for participants with Gilbert’s syndrome, ULN is considered to be 2.9 mg/ml).
f. Triplicate 12-lead ECG (taken after the volunteer has been 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.
5. Be willing to refrain from smoking (including tobacco, nicotine replacement therapy, e-cigarettes and marijuana) between the Screening visit and discharge from the clinic.
6. Female volunteers, must:
a. Be of nonchildbearing potential i.e., surgically sterilised (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 a follicle-stimulating hormone (FSH) level >40 IU/L at the screening visit), or
b. If of childbearing potential, must:
i. Have a negative pregnancy test at the screening visit and on admission to the clinic on Day-1.
ii. Agree not to attempt to become pregnant or donate ova from signing the consent form until at least 30 days after the last dose of the study drug.
iii. Agree to use adequate contraception (defined as use of a condom by the male partner combined with use of a highly effective method of contraception) from one month prior to screening until at least 30 days after the last dose of study drug, if not exclusively in a same-sex relationship or abstinent as a committed lifestyle
7. Male volunteers, must:
a. Agree not to donate sperm from signing the consent form until at least 90 days days after the last dose of study drug.
b. If engaging in sexual intercourse with a female partner who could become pregnant, agree to use adequate contraception (defined as use of a condom combined with use of a highly effective method of contraception) from signing the consent form until at least 90 days after the last dose of study drug.
c. If engaging in sexual intercourse with a female partner who is not of childbearing potential or a same-sex partner, agree to use a condom 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
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. History or presence of significant cardiovascular, pulmonary, hepatic, renal, haematological, 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. History of surgery or hospitalisation within 30 days prior to screening, or surgery planned during the study.
3. Acute infections within 4 weeks prior to screening or current infection that requires systemically absorbed antibiotic, antifungal, antiparasitic or antiviral medications.
4. 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.
5. Any history of malignant disease in the last 5 years (excludes surgically resected skin squamous cell or basal cell carcinoma).
6. Any screening laboratory result outside the normal laboratory reference range (as confirmed upon repeated testing) and deemed clinically significant by the PI.
7. Presence of clinically relevant immunosuppression from, but not limited to, immunodeficiency conditions such as common variable hypogammaglobulinemia.
8. 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 dosing.
9. 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.
10. History of risk factors for torsade de pointes (including a family history of long QT syndrome or sudden cardiac death) or clinically significant arrythmia.
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. If abnormal values are obtained, the assessment may be repeated once.
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 4 days 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, and use of any over-the-counter medication (including herbal products, nutritional, diet aids, vitamin supplements, minerals and hormone supplements) 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 2 g per day maximum for no more than 3 consecutive days).
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 dosing or earlier will be considered eligible for enrolment 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).

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 on Day 1, which corresponds to a study treatment (83-0060 or placebo). Sealed participant-specific code break envelopes will be produced by the unblinded statistician(s) and will be retained at the clinical facility in a secure, accessible location.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The allocation to 83-0060 or placebo will be performed using a block randomization algorithm and will be documented in the study randomization schedule. The randomization schedule will be prepared by an unblinded statistician and maintained under controlled access.
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
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
This study is a FIH study with 83-0060 and as such no formal sample size calculation was performed. The chosen sample size chosen is deemed adequate to evaluate all study endpoints.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
30/04/2024
Actual
30/04/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
64
Accrual to date
16
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 26560 0
Scientia Clinical Research - Randwick
Recruitment postcode(s) [1] 42602 0
2031 - Randwick

Funding & Sponsors
Funding source category [1] 315725 0
Commercial sector/Industry
Name [1] 315725 0
Trawsfynydd Therapeutics AU Pty Ltd
Country [1] 315725 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Trawsfynydd Therapeutics AU Pty Ltd
Address
Country
Australia
Secondary sponsor category [1] 317830 0
Commercial sector/Industry
Name [1] 317830 0
Avance Clinical Pty Ltd
Address [1] 317830 0
Country [1] 317830 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314588 0
Bellberry Human Research Ethics Committee D
Ethics committee address [1] 314588 0
https://bellberry.com.au/
Ethics committee country [1] 314588 0
Australia
Date submitted for ethics approval [1] 314588 0
31/01/2024
Approval date [1] 314588 0
01/03/2024
Ethics approval number [1] 314588 0
2024-01-096

Summary
Brief summary
This is a double-blind, placebo-controlled, First-in-Human Study study to assess the safety of 83-0060, and how this drug acts in the body in healthy volunteers. 83-0060 may be indicated for use in patients with SARS-CoV-2, but a trial of the drug in healthy volunteers is needed before trials in SARS-CoV-2 patients can proceed.

Who is it for?
You may be eligible for this study if you are aged 18 to 65 years and are in good general health without a clinically significant medical history.

Study details
All healthy volunteer participants who choose to enrol in this study will be assigned by chance to receive either a single or multiple doses of 83-0060 or placebo. All participants will have their vital signs checked (heart rate, blood pressure, temperature, etc), and will provide blood and urine samples for testing.

It is hoped this research will determine the maximum dose of 83-0060 that can be administered safely without causing severe reactions. Once the dose of 83-0060 has been determined in healthy volunteers, a trial investigating the efficacy of 83-0060 as a treatment for patients with SARS-CoV-2 may proceed.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 132106 0
Dr Christopher Argent
Address 132106 0
Scientia Clinical Research Ltd,
The Bright Building,
Level 5, Corner High & Avoca Streets,
Randwick NSW 2031, Australia
Country 132106 0
Australia
Phone 132106 0
+61 2 9382 5844
Fax 132106 0
Email 132106 0
christopher.argent@scientiaclinicalresearch.com.au
Contact person for public queries
Name 132107 0
Christopher Argent
Address 132107 0
Scientia Clinical Research Ltd,
The Bright Building,
Level 5, Corner High & Avoca Streets,
Randwick NSW 2031, Australia
Country 132107 0
Australia
Phone 132107 0
+61 2 9382 5844
Fax 132107 0
Email 132107 0
christopher.argent@scientiaclinicalresearch.com.au
Contact person for scientific queries
Name 132108 0
Christopher Argent
Address 132108 0
Scientia Clinical Research Ltd,
The Bright Building,
Level 5, Corner High & Avoca Streets,
Randwick NSW 2031, Australia
Country 132108 0
Australia
Phone 132108 0
+61 2 9382 5844
Fax 132108 0
Email 132108 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.