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This is a multi-centre, randomized, double-blind, placebo-controlled, dose escalation first in human (FIH) study in healthy adults and in patients with mild to moderate Alzheimer's disease. The study is designed to systematically assess the safety (including immunogenicity) and tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of AL002.
The study will be conducted in 2 phases:
In the single ascending dose (SAD) phase up to approximately 56 healthy adult participants will be sequentially enrolled into up to approximately 9 cohorts In the multiple-dose (MD) phase, approximately 32 patients with mild to moderate Alzheimer's disease will be enrolled in three cohorts.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| AL002 | Active Comparator | AL002 by intravenous (IV) infusion |
|
| Saline Solution | Placebo Comparator | placebo by intravenous (IV) infusion |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AL002 | Biological | Single-doses of AL002 in up to 9 dose-escalating cohorts |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Evaluation of safety and tolerability of AL002 measured by number of subjects with adverse events and Dose Limiting Adverse Event (DLAEs) | Incidence of adverse events and dose limiting Adverse Events during the DLAE observation period and/or study treatment periods. | 141 days |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics (PK) of AL002 | Serum and CSF concentration of AL002 at specified time points | 85 days |
| Maximum plasma concentration (Cmax) for AL002 | Evaluate Cmax for serum and CSF concentration of AL002 at specified time points |
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Inclusion Criteria:
For MD cohort
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Robert Paul, MD | Alector Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Brain Matters Research | Delray Beach | Florida | 33445 | United States | ||
| Compass Research - Orlando |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39444037 | Derived | Long H, Simmons A, Mayorga A, Burgess B, Nguyen T, Budda B, Rychkova A, Rhinn H, Tassi I, Ward M, Yeh F, Schwabe T, Paul R, Kenkare-Mitra S, Rosenthal A. Preclinical and first-in-human evaluation of AL002, a novel TREM2 agonistic antibody for Alzheimer's disease. Alzheimers Res Ther. 2024 Oct 23;16(1):235. doi: 10.1186/s13195-024-01599-1. |
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| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |
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| Saline Solution |
| Other |
Saline solution will be administered as a single infusion for each cohort in a ratio of 6 active and 2 placebo subjects for HV and 10 active and 2 placebo for patients |
|
| 85 days |
| Area under the curve concentration (AUC) for AL002 | Evaluate AUC for serum and CSF concentration of AL002 at specified time points | 85 days |
| Orlando |
| Florida |
| 32806 |
| United States |
| Compass Research - The Villages | The Villages | Florida | 32162 | United States |
| Columbia University | New York | New York | 10032 | United States |
| Nucleus Network Pty Ltd | Melbourne | Australia |
| University College London | London | United Kingdom |
| D024801 |
| Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |