None listed
Conditions
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.
Interventions
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 rand
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 the following doses: • SAD Cohort 1: 15 mg (under fasted conditions) • SAD Cohort 2: 50 mg (under fasted conditions) • SAD Cohort 3: 150 mg (under fasted conditions) • SAD Cohort 4: 300 mg (under fasted conditions) • SAD Cohort 5: 600 mg (under fasted conditions) • Optional SAD Cohort Xb: TBC (under fed conditions) Part B Multiple ascending dose (MAD): will comprise of 2 cohorts (MAD Cohorts 1 and 2). 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 once daily with the following doses: • MAD Cohort 1: 150 mg (Day 1 to Day 10) • MAD Cohort 2: 600 mg (Day 1 to Day 10) 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.
Sponsors
Trawsfynydd Therapeutics AU Pty Ltd (on behalf of Traws Pharma, Inc)
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver)
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
Yes
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 or semi-supine 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 and platelet 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 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. 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.
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) or a positive urine cotinine or carbon monoxide breath test 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).
Outcome results
None listed