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Trial registered on ANZCTR


Registration number
ACTRN12622000643774
Ethics application status
Approved
Date submitted
11/04/2022
Date registered
3/05/2022
Date last updated
20/01/2023
Date data sharing statement initially provided
3/05/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 1, Randomised, Double-Blind, Placebo-Controlled, First in Human Study of the Safety, Tolerability and Pharmacokinetics of AI-071 in Healthy Volunteers.
Scientific title
A Phase 1, Randomised, Double-Blind, Placebo-Controlled, First in Human Study of the Safety, Tolerability and Pharmacokinetics of AI-071 in Healthy Volunteers.
Secondary ID [1] 306589 0
AI-071-AU-01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
COVID-19 325580 0
Condition category
Condition code
Infection 322948 322948 0 0
Other infectious diseases
Respiratory 323422 323422 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 323090 0
Treatment: Drugs
Comparator / control treatment
Placebo will be identical in appearance to AI-071 and will contain 0.9% normal saline. 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 a single dose of AI-071 (6 participants) or placebo (2 participants) via intravenous infusion on Day 1.

Control group
Placebo

Outcomes
Primary outcome [1] 330716 0
To investigate the safety and tolerability of a single intravenous dose of AI-071 in healthy adult volunteers.
Timepoint [1] 330716 0
Safety endpoints include:
• Incidence, severity, and relationship of Adverse Events (AEs) and Serious Adverse Events (SAEs) (including withdrawals due to AEs) graded using the National Cancer Institute CommonTerminology Criteria for Adverse Events (NCI-CTCAE) (Version 5).- Timepoints: Day 1: pre-dose, 0, 0.5, 1, 2, 4, 6. 8, 12, 14, 24 hours then daily from Day 2 up to Day 42 post-dose End of Study Visit (EOS)/Early Termination Visit (ETV)
• Change from baseline in physical examination findings undertaken as in person examination - Timepoints: Screening, Day -1, Day 1: pre-dose, Day 2 24 hours (± 1 hour) following the start of infusion, Day 3, Day 7, Day 14, Day 21, Day 28 (if required) and Day 42 post-dose (EOS/ETV)
• Change from baseline in vital signs. Blood pressure and heart rate is assessed using a sphygmomanometer and bodytemperature by thermometer - Timepoints: Screening, Day-1, Day 1: pre-dose, 1, 2, 4, 6, 8, 12, 24 hours, Day 3, Day 7, Day 14, Day 21, Day 28 and Day 42 post-dose (EOS/ETV)
• Change from baseline in electrocardiogram (ECG) parameters; measured by triplicate 12 lead ECG - TImepoints: Screening, Day-1, Day 1: pre-dose, 2, 6, 24 hours, Day 3, Day 7, Day 14, Day 21, Day 28 and Day 42 post-dose (EOS/ETV)
• Change from baseline in clinical laboratory parameters (haematology, serum chemistry, and urinalysis) - Timepoints: Screening, Day -1, Day 1: 8 and 24 hours, Day 3, Day 7, Day 14, Day 21, Day 28 and Day 42 post-dose (EOS/ETV)
Secondary outcome [1] 407293 0
To measure the pharmacokinetics (PK) of AI-071 in serum following a single intravenous dose in healthy adult volunteers.

Serum PK endpoints include (but are not limited to):
• Maximum observed concentration (Cmax);
• Time to Cmax (Tmax);
• Area under the concentration-time curve from 0 to time of last quantifiable concentration (AUC0-t);
• Area under the concentration-time curve from 0 to infinity (AUC0-inf);
• Apparent terminal elimination half-life (t1/2);
• Terminal elimination rate constant (kel);
• Total apparent body clearance (CL/F);
• Apparent volume of distribution (Vz/F).
Timepoint [1] 407293 0
Timepoints: 'Day 1: pre-dose, 0.5, 2, 6, 24 hours post-dose, Day 7, Day 14, Day 21, Day 28 and Day 42 post-dose (EOS/ETV)'.
Secondary outcome [2] 407294 0
To assess the immunogenicity of AI-071. Concentration of AI-071 anti-drug antibodies (ADA) in serum
Timepoint [2] 407294 0
Timepoints: Day 1 pre-dose, Day 7, Day 28 and Day 42 post-dose (EOS/ETV). Only at ETV if deemed appropriate by the PI.

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key 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.

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)
Participants to be dosed will be assigned a randomisation number in accordance with the randomisation schedule. Participants who meet the study eligibility criteria will be assigned a randomisation number pre-dose on Day 1, which corresponds to a study treatment (AI-071 or placebo). . The randomization schedules will be prepared by unblinded statisticians and will be maintained under controlled access. As the study is double-blinded, 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 AI-071 or placebo will be performed using a block randomisation algorithm
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 the FIH study with AI-071 and as such no formal sample size calculation was performed.

The full analysis set will include all randomised participants who receive a dose of study drug (AI-071 or placebo) and have at least one post-dose assessment.

Participant disposition and background data, including demographics, relevant background, participation, compliance, and concomitant medication data, will be presented for all participants in the full analysis set.

Safety and tolerability data will be presented for all participants in the full analysis set.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
10/05/2022
Actual
24/05/2022
Date of last participant enrolment
Anticipated
31/08/2022
Actual
20/10/2022
Date of last data collection
Anticipated
30/12/2022
Actual
13/01/2023
Sample size
Target
40
Accrual to date
Final
40
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 22054 0
Q-Pharm Pty - Clive Berghofer Research Centre (CBCRC) - Herston
Recruitment postcode(s) [1] 37177 0
4007 - Herston

Funding & Sponsors
Funding source category [1] 310920 0
Commercial sector/Industry
Name [1] 310920 0
AcroImmune Australia Biotech Pty Ltd
Country [1] 310920 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
AcroImmune Australia Biotech Pty Ltd
Address
31 Jonathan St,
Macgregor QLD 4109
Country
Australia
Secondary sponsor category [1] 312214 0
Commercial sector/Industry
Name [1] 312214 0
Avance Clinical Pty Ltd
Address [1] 312214 0
Level 1, 2 Ann Nelson Drive
Thebarton, SA 5031
Country [1] 312214 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310479 0
The Alfred Human Research Ethics Committee
Ethics committee address [1] 310479 0
The Alfred Hospital
55 Commercial Rd,
Melbourne VIC 3004
Ethics committee country [1] 310479 0
Australia
Date submitted for ethics approval [1] 310479 0
24/03/2022
Approval date [1] 310479 0
11/04/2022
Ethics approval number [1] 310479 0

Summary
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.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 117814 0
Dr Richard Friend
Address 117814 0
Nucleus Network Brisbane Clinic
Level 5
Clive Berghofer Cancer Research Centre (CBRC Building)
300C Herston Rd
Herston, Queensland, 4006
Australia
Country 117814 0
Australia
Phone 117814 0
+61 737072720
Fax 117814 0
Email 117814 0
[email protected]
Contact person for public queries
Name 117815 0
Nucleus Network Brisbane
Address 117815 0
Level 5 Clive Berghofer Cancer Centre Research Centre,
300 Herston Road, Herston, QLD 4006
Country 117815 0
Australia
Phone 117815 0
+61 1800 243 733
Fax 117815 0
Email 117815 0
[email protected]
Contact person for scientific queries
Name 117816 0
Fang (Faye) Liu
Address 117816 0
AcroImmune Australia Biotech Pty Ltd
31 Jonathan St,
Macgregor QLD 4109
Country 117816 0
Australia
Phone 117816 0
+61 1300 515 379
Fax 117816 0
Email 117816 0
[email protected]

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


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.