Clinical trial NCT05642429: Study of AV-1959D, an Amyloid Beta Vaccine
Official title: A Phase I, Randomized, Double-Blind Study to Evaluate Safety and Tolerability of Amyloid-β Vaccine, AV-1959D, in Patients With Early Alzheimer's Disease.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Alzheimer Disease
Lead sponsor: Institute for Molecular Medicine
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
name: Clinartis
First posted: 2022-12-08
Enrollment: 48
Sex: ALL
Minimum age (years): 60
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: Phase 1 clinical trial of AV-1959 amyloid-β vaccine for Alzheimer's disease (AD).

Detailed description: The Phase I study is a randomized, multicenter, double-blind, placebo-controlled study consisting of 3 sequential cohorts to determine the safety and tolerability of AV-1959D at three doses compared to a placebo in patients with early AD

Eligibility criteria: 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 Aβ 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.

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.

Primary outcomes:
measure: Number of participants with Treatment-Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs)
timeFrame: Baseline up to Week 28 weeks
Secondary outcomes:
measure: Number of participants with clinically significant changes in vital signs
timeFrame: Baseline up to Week 28
measure: Number of participants with clinically significant changes in ECG results
timeFrame: Baseline up to Week 28
measure: Number of participants with clinically significant changes in laboratory test
timeFrame: Baseline up to Week 28
measure: Number of participants with clinically significant changes in physical examinations
timeFrame: Screening up to Week 28
measure: Number of participants with clinically significant changes in neurological examinations
timeFrame: Screening up to Week 28
measure: Number of participants with Vasogenic edema (ARIA-E)
timeFrame: Screening, Weeks 8 and 28
measure: Number of participants with New cerebral ischemic or hemorrhagic events (ARIA-H) or associated symptoms
timeFrame: Screening, Weeks 8 and 28
measure: Number of participants with Change from baseline in C-SSRS Score
timeFrame: Baseline, Weeks 12 and 28
measure: Immunological outcome
timeFrame: Baseline and up to Week 28 post start of immunization with AV-1959D
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Banner Alzheimer's Institute
state: Arizona
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital
state: California
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Wellington
country: United States
facility: Alzheimer's Research and Treatment Center
state: Florida
city: Decatur
country: United States
facility: Accel Research
state: Georgia
city: Princeton
country: United States
facility: Global Medical Institutes Princeton Medical Institute
state: New Jersey
Study officials:
affiliation: IMM
name: Michael Agadjanyan, PhD
role: STUDY_DIRECTOR
References: