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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05642429




Registration number
NCT05642429
Ethics application status
Date submitted
30/11/2022
Date registered
8/12/2022
Date last updated
1/10/2024

Titles & IDs
Public title
Study of AV-1959D, an Amyloid Beta Vaccine
Scientific title
A Phase I, Randomized, Double-Blind Study to Evaluate Safety and Tolerability of Amyloid-ß Vaccine, AV-1959D, in Patients With Early Alzheimer's Disease.
Secondary ID [1] 0 0
R01AG074983
Secondary ID [2] 0 0
IMM-AV1959D-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - AV-1959D
Treatment: Other - Placebo

Active comparator: AV-1959D 500 µg -

Active comparator: AV-1959D 1000 µg -

Active comparator: AV-1959D 2000 µg -

Placebo comparator: Placebo -


Treatment: Other: AV-1959D
Three doses of AV-1959D administered as a sterile suspension via intradermal injection

Treatment: Other: Placebo
Three doses of Placebo administered as a sterile suspension via intradermal injection
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants with Treatment-Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs)
Timepoint [1] 0 0
Baseline up to Week 28 weeks
Secondary outcome [1] 0 0
Number of participants with clinically significant changes in vital signs
Timepoint [1] 0 0
Baseline up to Week 28
Secondary outcome [2] 0 0
Number of participants with clinically significant changes in ECG results
Timepoint [2] 0 0
Baseline up to Week 28
Secondary outcome [3] 0 0
Number of participants with clinically significant changes in laboratory test
Timepoint [3] 0 0
Baseline up to Week 28
Secondary outcome [4] 0 0
Number of participants with clinically significant changes in physical examinations
Timepoint [4] 0 0
Screening up to Week 28
Secondary outcome [5] 0 0
Number of participants with clinically significant changes in neurological examinations
Timepoint [5] 0 0
Screening up to Week 28
Secondary outcome [6] 0 0
Number of participants with Vasogenic edema (ARIA-E)
Timepoint [6] 0 0
Screening, Weeks 8 and 28
Secondary outcome [7] 0 0
Number of participants with New cerebral ischemic or hemorrhagic events (ARIA-H) or associated symptoms
Timepoint [7] 0 0
Screening, Weeks 8 and 28
Secondary outcome [8] 0 0
Number of participants with Change from baseline in C-SSRS Score
Timepoint [8] 0 0
Baseline, Weeks 12 and 28
Secondary outcome [9] 0 0
Immunological outcome
Timepoint [9] 0 0
Baseline and up to Week 28 post start of immunization with AV-1959D

Eligibility
Key inclusion criteria
1. Male or female subjects from 60 to 85 years of age, both inclusive.
2. Mild cognitive impairment (MCI) due to Alzheimer's disease (AD), according to Albert et al., or mild AD dementia, according to McKhann et al., and must have the following:

* Mini-Mental State Examination (MMSE) score from 22 to 30;
* Clinical Dementia Rating (CDR) global score of 0.5 or 1.0.
3. A positive visual Aß positron emission tomography (PET) scan. Previously obtained PET scan (within 24 months of screening) is permissible and must be submitted to the central imaging reader to confirm that study inclusion criteria are met.
4. Subjects on approved AD medications (e.g., acetylcholine esterase inhibitors, memantine) are required to be on a stable dose for a minimum 3 months before baseline and with no dosage adjustments expected during the study. Continuation of subjects with dose adjustments for approved AD medications during the study may be allowed after discussion between the Investigator and the Medical Monitor.
5. The subject has a reliable study partner who will accompany the patient to all clinic visits during the study and, in the Investigator's opinion, has frequent and sufficient contact with the subject as to be able to provide accurate information about the subject's cognitive and functional abilities.
6. The subject's sight and hearing (hearing aid permissible) are sufficient for compliance with the study procedures.
7. Signed informed consent form by the subject and study partner prior to study participation.
Minimum age
60 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

1. Participation in another investigational drug or device study or treated with an investigational drug within 30 days or 5 half-lives, whichever is longer, before dosing.
2. Prior administration of any amyloid-beta or tau immunotherapy (vaccine, antibody)
3. Magnetic resonance imaging (MRI) showing evidence of any of the following:

* More than 1 lacunar infarct greater than 1.5 cm
* Any territorial infarct, including acute or chronic, greater than 1.5 cm
* Subjects who have a combined number of microbleeds and areas of leptomeningeal hemosiderosis (i.e., cumulative ARIA-H) on the MRI of > 5 (and should not include any disseminated leptomeningeal hemosiderosis)
* Subjects who have a presence of any other significant cerebral abnormalities, including ARIA-E, as assessed in the screening MRI scan.
4. 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.
5. 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.
6. Concurrent use of warfarin or other coumarin derivatives or a combination of acetylsalicylic acid and an anti-platelet agent (e.g., clopidogrel). Low dose of acetylsalicylic acid (=81 mg per day) is allowed.
7. Parenteral use of immunoglobulin preparations, blood products, plasma derivatives.
8. Any serious illness requiring systemic treatment and/or hospitalization within 4 weeks prior to study entry.
9. Any major or unstable illness, including unstable ischemic cardiovascular disease, or require use of excluded medications.
10. History/evidence of clinically relevant pathology related to 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 the subject's participation and follow-up in the clinical study.
11. Subjects with insulin-dependent diabetes.
12. Cardiac arrhythmias or palpitations [e.g., supraventricular tachycardia, atrial fibrillation, frequent ectopy, or sinus bradycardia]. Cardiac conduction abnormalities to be specified including prolonged QT interval and bundle branch blocks.
13. Subjects with pre-existing autoimmune diseases.
14. A medical condition that in the opinion of the Investigator might be a contributing cause of cognitive impairment.
15. History/evidence of severe local or systemic reactions to vaccination or significant allergic reactions.
16. History of seizure disorder.
17. Any other medical, psychological, social condition or diagnostic test which, in the opinion of the Investigator and Medical Monitor may lead to screen failure or prevent the subject from fully participating in the study, represent a concern for study compliance, or constitute a safety concern to the subject.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
27/02/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
7/11/2026
Actual
Sample size
Target
48
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
New Jersey

Funding & Sponsors
Primary sponsor type
Other
Name
Institute for Molecular Medicine
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Institute on Aging (NIA)
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/industry
Name [2] 0 0
Clinartis
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Phase 1 clinical trial of AV-1959 amyloid-ß vaccine for Alzheimer's disease (AD).
Trial website
https://clinicaltrials.gov/study/NCT05642429
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
Michael Agadjanyan, PhD
Address 0 0
IMM
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Roman Kniazev
Address 0 0
Country 0 0
Phone 0 0
7145963981
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05642429