None listed
Conditions
Brief summary
The key neuropathological findings of Alzheimer’s Disease are the accumulation of diffuse and neuritic amyloid plaques. In AD, it has become increasingly recognized that amyloid accumulation in the brain occurs decades before such symptoms as memory loss and personality change begin. AV-1959R vaccine is designed to induce production of anti-amyloid antibodies, that can prevent plaques formation. In this Phase I trial, the Sponsor will seek to determine the safety, tolerability, and immunogenicity of an active preventive vaccine, AV-1959R, targeting amyloid beta in healthy participants.
Interventions
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 ide
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.
Sponsors
Arvax Pty Ltd
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
40 Years to 60 Years
Healthy volunteers
Yes
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.
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.
Outcome results
None listed