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| ID | Type | Description | Link |
|---|---|---|---|
| 1R01AG092949-01 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Aging (NIA) | NIH |
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This is a Phase 1, multicenter, randomized, double-blind, placebo-controlled, multiple dose-escalating trial to evaluate the safety, tolerability, and immune response of AV-1980R, an investigational vaccine targeting tau protein, in participants with preclinical Alzheimer's disease. Up to 48 cognitively unimpaired adults aged 65-80 with biomarker evidence of early Alzheimer's disease will be enrolled into three ascending dose cohorts. The study is designed as a secondary prevention trial to test whether therapeutic immunization at the preclinical stage is safe, induces an immune response, and, exploratorily, may favorably affect biomarkers associated with disease progression.
This first-in-human study investigates AV-1980R, a MultiTEP-based active immunotherapy formulated with the adjuvant, as a secondary prevention approach for Alzheimer's disease. The study will randomize up to 48 participants aged 65-80 years in a 3:1 ratio to AV-1980R or placebo across three ascending dose cohorts (20 μg, 60 μg, 180 μg). Participants will receive four intramuscular doses at Weeks 0, 4, 12, and 36, with follow-up through Week 56.
Primary objectives are to evaluate safety and tolerability, monitored by adverse events, labs, ECGs, MRI, and neurological assessments. Secondary objectives include immunogenicity measured by anti-tau antibody titers. Exploratory endpoints include plasma biomarker and tau-PET changes.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| AV-1980R 20 µg Arm | Experimental | Participants receive 20 µg AV-1980R intramuscularly at Weeks 0, 4, 12, and 36. |
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| AV-1980R 60 µg Arm | Experimental | Participants receive 60 µg AV-1980R intramuscularly at Weeks 0, 4, 12, and 36. |
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| AV-1980R 180 µg Arm | Experimental | Participants receive 180 µg AV-1980R intramuscularly at Weeks 0, 4, 12, and 36. |
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| Placebo Arm | Placebo Comparator | Participants receive placebo injections (10 mM phosphate buffer with the adjuvant, no antigen) at Weeks 0, 4, 12, and 36. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AV-1980R 20 µg | Biological | MultiTEP-based investigational tau vaccine formulated with the adjuvant. The vaccine is designed to elicit anti-tau antibodies in participants with preclinical Alzheimer's disease. |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Frequency, severity, and relationship of TEAEs and SAEs; safety assessments include labs, vitals, ECGs, MRI, and neurological exams. | Baseline through Week 56 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants with Clinically Significant Changes in Vital Signs | Number of participants with clinically significant abnormalities or changes in blood pressure, heart rate, respiratory rate, or body temperature. | Baseline through Week 56 |
| Number of Participants with Clinically Significant Changes in ECG Results |
| Measure | Description | Time Frame |
|---|---|---|
| Change from Baseline in Plasma Biomarker Concentrations (pg/mL) | Change in plasma concentrations of Aβ42, Aβ40, pTau217, pTau181, pTau231, total tau (t-tau), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP), reported in pg/mL. | Baseline through Week 56 |
| Change from Baseline in Immunoglobulin Isotypes and Subclasses (mg/dL) |
Inclusion Criteria:
Male or post-menopausal/surgically sterile female, 65-80 years of age.
Cognitively unimpaired with preclinical Alzheimer's disease:
CDR global score = 0. MMSE ≥ 26. WMS-R LM II ≥ 6. Amyloid Probability Score 2 (APS2) > 54 (PrecivityAD2™). Adequate vision/hearing to comply with study procedures. Stable concomitant medications if applicable. Signed informed consent.
Exclusion Criteria:
MRI abnormalities: >1 large lacunar infarct, territorial infarct, >5 microbleeds, ARIA-E, or other significant pathology.
Contraindications to MRI (e.g., pacemaker, metallic implants, severe claustrophobia).
Serious illness or hospitalization within 4 weeks prior to enrollment. Clinically significant cardiovascular, endocrine, hematologic, autoimmune, or neurological disease.
Insulin-dependent diabetes, significant arrhythmias, or seizure disorder. Positive C-SSRS (score ≥ 3). Prior tau or amyloid-beta immunotherapy within 1 year. Immunosuppressive or anticoagulant use that could interfere with study safety. Clinically significant lab abnormalities or positive HIV, HBV, or HCV screening.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Roman Kniazev | Contact | 7145963981 | rkniazev@immed.org | |
| Anahit Ghochikyan | Contact | 7145963981 | aghochikyan@immed.org |
| Name | Affiliation | Role |
|---|---|---|
| Michael Agadjanyan, PhD | Institute MM | Principal Investigator |
| Roman Kniazev | Institute MM | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Comprehensive Center for Brain Health | Not yet recruiting | Boca Raton | Florida | 33433 | United States |
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| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| D057180 | Frontotemporal Dementia |
| D009410 | Nerve Degeneration |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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Participants are randomized in a 3:1 ratio to receive AV-1980R or placebo across three ascending dose cohorts. Each participant gets one assigned intervention in parallel with others.
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Participants are randomized 3:1 within each cohort to AV-1980R or placebo. Arms reflect three dose levels (20, 60, 180 µg) and a pooled placebo; dosing at Weeks 0, 4, 12, and 36 with follow-up to Week 56.
| AV-1980R 60 µg | Biological | MultiTEP-based tau vaccine formulated with the adjuvant, 60 µg per dose; intramuscular injections at Weeks 0, 4, 12, and 36; secondary-prevention immunotherapy in preclinical AD. |
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| AV-1980R 180 µg | Biological | MultiTEP-based tau vaccine formulated with the adjuvant, 180 µg per dose; intramuscular injections at Weeks 0, 4, 12, and 36; secondary-prevention immunotherapy in preclinical AD. |
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| Placebo | Other | 10 mM phosphate buffer formulated with the adjuvant; intramuscular injections at Weeks 0, 4, 12, and 36; no active antigen. |
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Number of participants with new or worsening clinically significant ECG abnormalities. |
| Baseline through Week 56 |
| Number of Participants with Clinically Significant Changes in Laboratory Tests | Number of participants with new or worsening abnormalities in hematology, serum chemistry, coagulation, or urinalysis results. | Baseline through Week 56 |
| Number of Participants with Clinically Significant Changes in Physical Examinations | Number of participants with new or worsening abnormal findings on physical examination. | Baseline through Week 56 |
| Number of Participants with Clinically Significant Changes in Neurological Examinations | Number of participants with new or worsening abnormal neurological findings. | Baseline through Week 56 |
| Incidence of Amyloid-Related Imaging Abnormalities (ARIA-E and ARIA-H) | Number of participants with vasogenic edema (ARIA-E), effusions, ischemic events, hemorrhagic events, or associated clinical symptoms detected on MRI. | Baseline through Week 56 |
| Change from Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) | Change from baseline in suicidality assessment using the Columbia-Suicide Severity Rating Scale (C-SSRS; range: 0-25, with higher scores indicating greater severity of suicidal ideation and behavior). | Baseline, Weeks 12, 36, 40, and 56 |
| Change from Baseline in Serum Anti-Tau Antibody Concentrations | Quantification of anti-tau antibody titers induced by AV-1980R vaccination. | Baseline through Week 56 |
| Detection of T Helper (Th) Cell Responses Specific to MultiTEP Platform | Presence of antigen-specific Th cell responses against the MultiTEP vaccine platform. | Baseline through Week 56 |
| Detection of Autoreactive Th-Cell Responses Specific to Tau | Presence of autoreactive Th cell responses directed against tau epitopes. | Baseline through Week 56 |
Change in serum concentrations of IgM, total IgG, and IgG subclasses (IgG1, IgG2, IgG3, IgG4), reported in mg/dL |
| Baseline through Week 56 |
| Phenotyping of Activated T Cells | Characterization of activated T cell subsets by flow cytometry. | Baseline through Week 56 |
| T Cell Proliferative Response | Assessment of proliferative capacity of T cells following antigen stimulation. | Baseline through Week 56 |
| Polarization of Cellular Responses | Cytokine production by activated T cells to evaluate polarization of Th1/Th2/Th17 responses. | Baseline through Week 56 |
| Change from Baseline in Plasma Biomarker Ratios | Change in plasma biomarker ratios including Aβ42/40 ratio and Aβ42/tau ratios (unitless) | Time Frame: Baseline through Week 56 |
| Alzheimer's Research and Treatment Center (Stuart) | Recruiting | Stuart | Florida | 34996 | United States |
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| Alzheimer's Research and Treatment Center (Wellington) | Recruiting | Wellington | Florida | 33414 | United States |
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| D024801 |
| Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D057174 | Frontotemporal Lobar Degeneration |
| D057177 | TDP-43 Proteinopathies |
| D057165 | Proteostasis Deficiencies |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |