Study of AV-1959, an Amyloid Beta Vaccine

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

Detailed Description
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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.

Official Title
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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.

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Biological: AV-1959D
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects from 60 to 85 years of age. Mild cognitive impairment (MCI) due to Alzheimer's disease (AD), 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. A positive visual Aβ positron emission tomography (PET) scan. Exclusion Criteria: 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. Prior administration of any amyloid-beta or tau immunotherapy (vaccine, antibody) Magnetic resonance imaging (MRI) showing evidence of existing safety issues. Use of immunomodulatory or growth-stimulating factors within 30 days prior to study entry. Any serious illness requiring systemic treatment and/or hospitalization within 4 weeks prior to study entry. Any major or unstable illness, including unstable ischemic cardiovascular disease, or require the use of excluded medications. Subjects with insulin-dependent diabetes. Subjects with pre-existing autoimmune diseases. A medical condition that in the opinion of the Investigator might be a contributing cause of cognitive impairment. History/evidence of severe local or systemic reactions to vaccination or significant allergic reactions. History of seizure disorder.

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: AV-1959D 500 μg<br> | Biological: AV-1959D<br>* Three doses of AV-1959D administered as a sterile suspension via intradermal injection<br>|
| Active Comparator: AV-1959D 1000 μg<br> | Biological: AV-1959D<br>* Three doses of AV-1959D administered as a sterile suspension via intradermal injection<br>|
| Active Comparator: AV-1959D 2000 μg<br> | Biological: AV-1959D<br>* Three doses of AV-1959D administered as a sterile suspension via intradermal injection<br>|
| Placebo Comparator: Placebo<br> | Biological: Placebo<br>* Three doses of Placebo administered as a sterile suspension via intradermal injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Treatment-Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs) |  | Baseline up to Week 28 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with clinically significant changes in vital signs |  | Baseline up to Week 28 | 
| Number of participants with clinically significant changes in ECG results |  | Baseline up to Week 28 | 
| Number of participants with clinically significant changes in laboratory test |  | Baseline up to Week 28 | 
| Number of participants with clinically significant changes in physical examinations |  | Screening up to Week 28 | 
| Number of participants with clinically significant changes in neurological examinations |  | Screening up to Week 28 | 
| Number of participants with Vasogenic edema (ARIA-E) |  | Screening, Weeks 8 and 28 | 
| Number of participants with New cerebral ischemic or hemorrhagic events (ARIA-H) or associated symptoms |  | Screening, Weeks 8 and 28 | 
| Number of participants with Change from baseline in C-SSRS Score |  | Baseline, Weeks 12 and 28 | 
| Concentration of possibly harmful autoreactive Th cell responses specific to Aβ |  | Baseline, Week 8 | 
| Concentration of Serum anti-Aβ antibodies |  | Baseline up to Week 28 post start of immunization with AV-1959D | 
| Concentration of Th cell responses specific to MultiTEP platform |  | Baseline, Week 8 |