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Trial registered on ANZCTR


Registration number
ACTRN12624000737538
Ethics application status
Approved
Date submitted
17/05/2024
Date registered
14/06/2024
Date last updated
29/09/2024
Date data sharing statement initially provided
14/06/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase I Study of AV-1959R, an Amyloid Beta Vaccine in Healthy Participants
Scientific title
A Phase I, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability and Immunogenicity of AV-1959R in Healthy Participants
Secondary ID [1] 312170 0
AU-AV1959R-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alzheimer's Disease 333820 0
Condition category
Condition code
Neurological 330490 330490 0 0
Alzheimer's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a Phase 1, randomized, double-blind, placebo-controlled, multiple dose-escalating trial consisting of 2 ascending dose cohorts in healthy male and female participants, 40-60 years of age.
Volunteers will receive the investigational product, AV1959R recombinant vaccine, through a single intramuscular injection into the deltoid muscle of their preferred arm administered by a study nurse. Before immunization, the volunteers will undergo Screening visits within 4 weeks (up to 28 days) to identify eligible participants. Screening procedures may be performed in two or more screening visits. MRI examination for determination of subject eligibility will be performed at the later stage of screening.
A total of 16 volunteers will be enrolled into the study in one of two dose cohorts: 100mcg or 300mcg. Eligible participants will be randomly assigned in a 3:1 ratio to receive 3 intramuscular injections of either AV-1959R or placebo (a medication with no active drug in it) both formulated with Advax-CpG55.2 adjuvant (a substance that enhances the body's immune response to a vaccine) at baseline (Week 0), Weeks 4 and 14 and undergo follow-up visit at Week 22.
Each dose of study drug will be prepared by the pharmacist per the pharmacy manual and
administered by designated study personnel. The administration times as well as any
interruptions in dosing will be recorded. The Clinical Research Associate will review pharmacy and clinical site records to monitor protocol compliance.
Intervention code [1] 328613 0
Prevention
Intervention code [2] 328614 0
Treatment: Drugs
Comparator / control treatment
The study is Placebo controlled. Participants in the placebo group will be injected with Advax-CpG55.2 adjuvant (a substance that enhances the body's immune response to a vaccine).
Control group
Placebo

Outcomes
Primary outcome [1] 338263 0
The number of participants with Treatment-Emergent Adverse Events or Serious Adverse Events. Treatment-Emergent Adverse Events and Serious Adverse Events, will be assessed together as a composite primary outcome. Possible adverse events include, but not limited to neurological abnormalities, fatigue, fever and gastrointestinal disorders assessed by the study physician, ARIA in the brain assessed by MRI,
Timepoint [1] 338263 0
Assessments of injection site reactions on Immunization Days will be performed at 30 min, 1 hour, 2 hours and 4 hours post-dose (±15 minutes)
Clinical examinations, ECG and laboratory tests will be performed on the days:
1st - 1st immunization day
15th - follow-up,
28th - 2nd immunization day,
42nd - follow-up,
98th - 3rd immunization,
112th - follow-up,
154th - follow-up.
MRI will be performed as baseline before immunization and at week 22nd as follow-up.
Secondary outcome [1] 435199 0
Serum anti- Aß antibodies concentrations, i.e., IgM, total IgG and IgG subclasses (IgG1, IgG2, IgG3, and IgG4).
Timepoint [1] 435199 0
Blood samples will be collected on the days: 1, 42, 98, 112, 140 and 154.
Secondary outcome [2] 435727 0
Serum anti-MultiTEP antibodies concentrations, i.e., IgM, total IgG and IgG subclasses (IgG1, IgG2, IgG3, and IgG4).
Timepoint [2] 435727 0
Blood samples will be collected on the days: 1, 42, 98, 112, 140, 154.

Eligibility
Key inclusion criteria
1. Body mass index (BMI) between 18.0 and 32.0 kg/m2 at Screening visit
2. Medically healthy with no clinically significant medical history, abnormalities in physical examination, laboratory variables, vital signs, ECG or MRI at the time of Screening and Baseline (if applicable), as deemed by the Investigator or designee.
3. Signed informed consent form by the participant prior to initiation of any study-related procedures.
4. If female of non-childbearing potential, must meet at least one of the following criteria:
4.1. post-menopausal status defined as amenorrhea for at least 12 months prior to study drug dosing in absence of any exogenous hormonal treatments and follicle stimulating hormone (FSH) levels in the laboratory defined post-menopausal range.
4.2. subject report of surgical sterilization (i.e., hysterectomy, bilateral tubal ligation, bilateral oophorectomy/ salpingectomy) at least 6 weeks prior to Day 1.
5. If male, must have had a vasectomy 90 days prior to the Screening visit with a follow up negative sperm count, or agree to not donate sperm for 90 days after the last dose of study drug and, if engaging in vaginal sexual intercourse with a female partner of childbearing potential, agree to use a condom in addition to the female partner must use a highly effective method of birth control (e.g. intrauterine device, diaphragm with spermicide, hormonal contraceptives) throughout the duration of the study treatment period and for 90 days after the last dose of study drug.
6. Ability, in the opinion of the investigator, to understand the nature of the trial and comply with protocol requirements, including the prescribed dosage regimens, scheduled visits, laboratory tests, and other trial procedures.
Minimum age
40 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
A subject will be excluded from participation in this study if he or she meets any of the following criteria:
1. Any clinically significant medical history or observations at the time of Screening visit not specifically excluded in other criteria that, in the opinion of the Investigator or designee, may confound the results of the study, compromise the safety of the subject or otherwise render the subject unsuitable for participation.
2. Magnetic resonance imaging (MRI) showing evidence of any of the following at the Screening:
2.1. 1 or more small non-cortical lacunar infarct greater than 1.0 cm
2.2. Any territorial infarct including acute or chronic
2.3. Subjects who have microbleeds and areas of leptomeningeal hemosiderosis
2.4. Subjects who have a presence of any other significant cerebral abnormalities, including Amyloid Related Imaging Abnormalities characterized by edema and effusion (ARIA-E), as assessed in the screening MRI scan.
3. Contraindications for MRI scanning, including implanted metallic devices (e.g., non-MRI-safe cardiac pacemaker or neurostimulator; some artificial joints metal pins; surgical clips; or other implanted metal parts), or claustrophobia or discomfort in confined spaces.
4. Any serious illness requiring systemic treatment and/or hospitalization within 4 weeks prior to study entry.
5. History/evidence of clinically relevant pathology related to the cardiovascular system, respiratory tract, gastrointestinal tract, endocrinology, immunology, hematology, or any other systemic disorder/major surgeries that, in the opinion of the Investigator, would confound participation and follow-up.
6. History or presence of any of the following:
6.1. clinically significant acute illness or surgery within the previous 3 months of Day 1.
6.2. hypersensitivity reaction or anaphylaxis to any medication to be of clinical significance to the current study or compromise the safety of the subject in the opinion of the Investigator
6.3. history or suspicion of routine or chronic drug or alcohol abuse or dependence within 1 year prior to Day 1 based on subject report; excessive alcohol intake (defined as routine weekly intake of greater than 21 glasses/units per week, with one unit=150 mL of wine or 360 mL of beer or 45 mL of 45% alcohol.
7. Clinically significant laboratory abnormalities at Screening visit, including (but not limited to):
7.1. hemoglobin, hematocrit, total white blood count (WBC) or platelet count below the lower limit of the normal range
7.2. alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >1.5 times the upper limit of the normal range
7.3. serum creatinine above the upper limit of the normal range or estimated creatinine clearance <90 mL/minute as calculated by the Cockcroft-Gault equation
7.4. positive testing for human immunodeficiency virus (HIV-1 or -2), hepatitis B surface antigen (HBsAg), or positive testing for hepatitis C (HCV)
Clinical laboratory tests may be repeated as per Investigator’s discretion.
8. Systolic blood pressure (BP) >160 millimeters of mercury (mmHg), or <90 mmHg; diastolic BP >95 mmHg or <50 mmHg blood at Screening visit or Day 1. Vital signs may be repeated as per Investigator’s judgement.
9. Seated heart rate less than 45 beats per minute (bpm) or higher than 100 bpm at the Screening visit or Day 1. Vital signs may be repeated as per Investigator’s judgement.
10. ECG with QTcF interval duration equal or greater than 450 msec for males and 470 msec for females obtained after at least 5 minutes in a supine or semi-recumbent position at quiet rest at Screening visit or Day 1.
11. Any other medical, psychological, or social condition that, in the opinion of the Investigator, would prevent the participant from fully participating in the study would represent a concern for study compliance or would constitute a safety concern to the participant.
12. Participation in another investigational drug study or treatment with an investigational drug within 30 days or 5 half-lives, whichever is longer, before dosing.
13. Prior administration of any tau or amyloid-beta immunotherapy (vaccine, antibody) within 1 year prior to Screening.
14. The use of immunomodulatory or growth-stimulating factors such as systemic corticosteroids, cyclosporine, methotrexate, azathioprine, anti-CD25 antibody, GM-CSF, C-CSF, interferon (IFN), or interleukin-2 (IL-2) within 30 days prior to study entry.
15. Chronic use (>3 months) of warfarin, other coumarin derivatives, anticoagulants, or an anti-platelet agent (e.g., clopidogrel).
16. Parenteral use of immunoglobulin preparations, blood products, and plasma derivatives.
17. History/evidence of severe local or systemic reactions to vaccination or significant allergic reactions.
18. Female of childbearing potential.
19. Any skin condition and/or tattoo that may interfere with the evaluation of safety at the injection site.

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)
Allocation involves contacting the holder of the allocation schedule who is "off-site" or at central administration site. The person undertaking randomisation will be a non-clinician removed from the care of the patient.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomization sequence will be created by computer
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



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

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
21/06/2024
Actual
23/08/2024
Date of last participant enrolment
Anticipated
31/10/2024
Actual
Date of last data collection
Anticipated
30/04/2025
Actual
Sample size
Target
16
Accrual to date
2
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 26552 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment postcode(s) [1] 42592 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 316536 0
Commercial sector/Industry
Name [1] 316536 0
Clinartis Clinical Research Organization
Country [1] 316536 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Arvax Pty Ltd
Address
Country
Australia
Secondary sponsor category [1] 318716 0
None
Name [1] 318716 0
Address [1] 318716 0
Country [1] 318716 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 315329 0
Bellberry Human Research Ethics Committee H
Ethics committee address [1] 315329 0
Ethics committee country [1] 315329 0
Australia
Date submitted for ethics approval [1] 315329 0
04/12/2023
Approval date [1] 315329 0
06/02/2024
Ethics approval number [1] 315329 0

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

Contacts
Principal investigator
Name 134358 0
Dr Michele DeSciScio
Address 134358 0
CMAX Clinical Research, Ground Floor, 21-24 North Terrace, Adelaide SA 5000
Country 134358 0
Australia
Phone 134358 0
+610422447902
Fax 134358 0
Email 134358 0
[email protected]
Contact person for public queries
Name 134359 0
Alexander Grinberg
Address 134359 0
Arvax Pty Ltd, Level 5, 63 Pirie Street, Adelaide, SA 5000
Country 134359 0
United States of America
Phone 134359 0
+14152866530
Fax 134359 0
Email 134359 0
[email protected]
Contact person for scientific queries
Name 134360 0
Hovhannes Madoyan
Address 134360 0
Clinartis LLC, 1930 Harrison Street, Suite 308, Hollywood, FL 33020
Country 134360 0
United States of America
Phone 134360 0
+18184918365
Fax 134360 0
Email 134360 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


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.