None listed
Conditions
Brief summary
This is a Phase I, single dose escalation clinical trial conducted in healthy volunteers. The safety, tolerability, and PK of AI-071 following a single intravenous administration in healthy volunteers will be evaluated using a randomised, double-blind, placebo-controlled trial design. A total of up to 40 healthy participants are planned to be enrolled into 5 cohorts (8 participants per cohort). Eligible participants will be randomised to receive single ascending doses of AI-071 or placebo. Dose escalation will be conducted in a total of 5 dose levels. At each dose level, participants will be randomised to receive a single dose of AI-071 (6 participants) or placebo (2 participants). The starting dose, dose increments and dose range to be evaluated are based on available nonclinical data. AI-071 dose levels in the range of 60 to 960 mg will be investigated. Dosing in each cohort will start with 2 sentinel participants with one of the 2 sentinels randomised to receive AI-071 and the other randomised to receive placebo. The safety and tolerability of each sentinel participant will be monitored in the clinic until Day 2 and will be reviewed prior to dosing the remainder of participants in each cohort. Participants will be confined at the clinical facility from Day -1 through to Day 2. Participants will be discharged following completion of all safety and PK assessments on Day 2.
Interventions
A total of up to 40 healthy volunteers are planned to be enrolled into 5 cohorts (8 participants per cohort). Dose escalation will be conducted in a total of 5 dose levels as follows:
Cohort 1: 60 mg
Cohort 2: 120 mg
Cohort 3: 240 mg
Cohort 4: 480 mg
Cohort 5: 960 mg
At each dose level, participants will be randomised to receive via intravenous infusion, a single dose of AI-071 (6 participants) or placebo (2 participants). The starting dose, dose increments and dose range to be evaluated are
A total of up to 40 healthy volunteers are planned to be enrolled into 5 cohorts (8 participants per cohort). Dose escalation will be conducted in a total of 5 dose levels as follows: Cohort 1: 60 mg Cohort 2: 120 mg Cohort 3: 240 mg Cohort 4: 480 mg Cohort 5: 960 mg At each dose level, participants will be randomised to receive via intravenous infusion, a single dose of AI-071 (6 participants) or placebo (2 participants). The starting dose, dose increments and dose range to be evaluated are based on available nonclinical data. Healthy volunteers will be screened between Day -28 and Day -2, inclusive. Participants will be admitted to the clinical facility on Day -1 with dosing to occur on the following day, Day 1. All participants will be dosed under fasted conditions. For fasted administration of AI-071, all participants will undertake an overnight fast of at least 10 hour prior to the dose. Water will be allowed during the fasting period Adherence to the intervention will be done via drug accountability.
Sponsors
AcroImmune Australia Biotech Pty Ltd
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 55 Years
Healthy volunteers
Yes
Inclusion criteria
Healthy volunteers will be included in this study if they satisfy all of the following criteria as assessed at the screening visit or prior to administration of the first dose on study Day 1: 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 55 years of age (inclusive) at screening. 3. Body mass index greater than or equal to 18.0 and less than or equal to 30.0 kg/m2, with a body weight (to 1 decimal place) greater than or equal to 50 kg at screening. 4. Be non-smokers (including tobacco, e-cigarettes and marijuana) for at least 6 months prior to first study drug administration and have a negative test for cotinine at the screening visit and at check-in on Day -1. 5. Medically healthy without clinically significant abnormalities (in the opinion of the PI) at the screening visit and prior to dosing at the timepoints indicated in the Schedules of Assessments (SoA), including: a. Physical examination without any clinically significant findings; b. Systolic blood pressure in the range of 90 to 140 mmHg (inclusive) and diastolic blood pressure in the range of 60 to 90 mmHg (inclusive) after 5 minutes in supine (or semi-supine) position; c. Heart rate in the range of 55 to 100 bpm (inclusive) after 5 minutes rest in supine (or semi-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 (any of the routine laboratory test may be repeated at the discretion of the PI); f. Triplicate 12-lead ECG (taken after the volunteer has been supine (or semi-supine) for at least 5 minutes) with a QT interval corrected using the Fridericia method (QTcF) greater than or equal to 450 msec for males and less than or equal to 470 msec for females and no clinically significant abnormalities. 6. Female volunteers must: a. Be of nonchildbearing potential i.e., be surgically sterilised (hysterectomy, bilateral salpingectomy, bilateral oophorectomy at least 6 weeks before screening) or be postmenopausal, where menopause is defined as 12 months of amenorrhea in the absence of other biological causes. Females under the age of 55 years must have a documented serum follicle-stimulating hormone (FSH) level > 40mIU/mL to confirm menopause (females who are taking Hormone Replacement Therapy (HRT) should provide evidence that they are post-menopausal or should be excluded as their post-menopausal status cannot be confirmed by measuring FSH - alternatively they would need to stop HRT to allow FSH to be measured). b. If of childbearing potential (defined as any female who has experienced menarche and who has not undergone surgical sterilisation and is not postmenopausal), the participant: • Must have a negative serum test at the screening visit and a negative urine pregnancy test within 24 hours prior to the start of study drug; • Must not be breastfeeding, lactating or planning pregnancy during the study period; • Must agree not to attempt to become pregnant; • If not exclusively in same-sex relationships, must agree to use adequate contraception (which is defined as use of a condom by the male partner combined with use of a highly effective method of contraception by the female partner; refer to Appendix 5. Highly Effective Forms of Contraception) after signing consent, during the study, and at least 30 days after the last dose of study drug; • Must agree to not donate ova for at least 30 days after the last dose of study drug. 7. Male participants, if not surgically sterilised, must agree to: a. Not donate sperm after signing consent, during the study, and at least 90 days after the last dose of study drug; b. If engaging in sexual intercourse with a female partner who could become pregnant, use a condom in addition to having the female partner use a highly effective contraceptive method (refer to Appendix 5. Highly Effective Forms of Contraception). 8. Must have received at least double vaccination against COVID-19. 9. Have suitable venous access for blood sampling. 10. Be willing and able to comply with all study assessments and adhere to the protocol schedule and restrictions.
Exclusion criteria
Healthy volunteers will be excluded from this study if there is evidence of any of the following at the screening visit or prior to administration of the first dose on study Day 1: 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 (participants with resolved childhood asthma may be included in the study). 2. Current infection that requires systemically absorbed antibiotic, antifungal, antiparasitic or antiviral medications. 3. Any history of malignant disease in the last 10 years (excludes surgically resected skin squamous cell or basal cell carcinoma). 4. Presence of clinically relevant immunosuppression from, but not limited to, immunodeficiency conditions such as common variable hypogammaglobulinemia. 5. Use of or plans to use systemic immunosuppressive (e.g., corticosteroids, methotrexate, azathioprine, cyclosporine) or immunomodulating medications (e.g., interferon) during the study or within 3 months prior to the first study drug administration (prior use of nasal sprays for hayfever may be permitted at the discretion of the PI). 6. History of risk factors for torsade de pointes (including a family history of long QT syndrome or sudden cardiac death) or a known arrythmia. 7. Liver function test results elevated more than 1.5-fold above the upper limit of normal (ULN) for gamma glutamyl transferase (GGT), bilirubin (total, conjugated and unconjugated), alkaline phosphatase (ALP), aspartate aminotransferase (AST) or alanine aminotransferase (ALT). Volunteers with ALP and/or ALT/AST above the limits specified may be included, at the discretion of the PI, if the levels are unaccompanied by clinical signs and are determined to be normal variants. 8. Positive test results for active human immunodeficiency virus (HIV-1 or HIV-2), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies at the screening visit. 9. Presence or having sequelae of gastrointestinal, liver, kidney, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs (prior gall bladder and/or appendix removal is not exclusionary if deemed appropriate by the PI). 10. Estimated creatinine clearance (CrCl) < 60 mL/min using the Cockcroft-Gault formula or serum creatinine more than 1.5-fold above the ULN. 11. History of substance abuse or alcohol abuse within 12 weeks prior to the screening visit (defined as more than an average of 14 standard drinks per week or regular consumption of more than 4 standard drinks on any one day; where 1 standard drink is 10 g of pure alcohol and is equivalent to 285 mL beer [4.9% Alc./Vol], 100 mL wine [12% Alc./Vol], 30 mL spirit [40% Alc./Vol]). 12. Positive drugs of abuse or alcohol breath test results at the screening visit or at check-in (Day -1). 13. Use of any prescription or over-the-counter medication (including herbal products, and hormone supplements) within 10 days or 5 half-lives of the medication (whichever is longer) prior to the first study drug administration – exceptions include 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), 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. 14. 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 PI, would interfere with the volunteer’s ability to participate in the trial. 15. Known hypersensitivity to any of the study drug ingredients. 16. Use of any vaccinations within 14 days (within 4 weeks for live virus vaccines) prior to the first study drug administration. 17. 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). 18. Females who are breastfeeding or planning to breast feed at any time during the study. 19. 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. 20. Treatment with an investigational drug in another clinical trial within 60 days or 5 half-lives of the other investigational drug (whichever is longer) prior to the first administration of study drug in this trial. 21. Any other condition or prior therapy that in the opinion of the PI 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.
Outcome results
None listed