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Study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of ARO-MAPT-SC compared to placebo in adult healthy volunteers and in participants with early Alzheimer's disease (AD), defined as mild cognitive impairment due to AD and mild AD dementia.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ARO-MAPT-SC | Experimental | ARO-MAPT-SC injection |
|
| Placebo | Placebo Comparator | Sterile normal saline (0.9%) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ARO-MAPT-SC | Drug | • single or multiple doses of ARO-MAPT-SC by subcutaneous (SC) injection |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants with Treatment-Emergent Adverse Events (TEAEs) Over Time | Through End of Study (EOS), Day 270 |
| Measure | Description | Time Frame |
|---|---|---|
| PK of ARO-MAPT-SC: Maximum Observed Plasma Concentration (Cmax) | Through 48 hours postdose | |
| PK of ARO-MAPT-SC: Time to Maximum Plasma Concentration (Tmax) | Through 48 hours postdose | |
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Inclusion Criteria (All Participants):
Inclusion Criteria (Alzheimer's Disease):
Adults aged 50 to 80 years of age with a clinical diagnosis of early AD and plasma, CSF, or imaging biomarkers consistent with the diagnosis
If participant is on AD medications, the doses must be stable for ≥weeks prior to Screening.
a. Participants with early AD are not required to be on AD medications.
Have a reliable and competent caregiver or trial partner who is ≥18 years of age, able and willing to accompany the participant to study visits involving informant-based assessments, to be available to site staff by telephone as needed, and in the opinion of the Investigator, be sufficiently familiar with the participant throughout the study in order to provide accurate and reliable information relevant to study outcome measures
Exclusion Criteria (All Participants):
Note: Additional inclusion/exclusion criteria may apply per protocol.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Medical Monitor | Contact | 626-304-3400 | AROMAPT-SC-1001@arrowheadpharma.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site 3 | Recruiting | East York | Ontario | M4G 3E8 | Canada | |
| Research Site 2 |
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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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| Placebo |
| Drug |
• calculated volume to match active treatment by SC administration |
|
| PK of ARO-MAPT-SC: Area Under the Plasma Concentration (AUC) Versus Time Curve From Time Zero to 24 Hours (AUC0-24) |
| Through 24 hours postdose |
| PK of ARO-MAPT-SC: AUC Versus Time Curve From Time Zero to 48 Hours (AUC0-48) | Through 48 hours postdose |
| PK of ARO-MAPT-SC: AUC Versus Time Curve From Time Zero to the Last Quantifiable Plasma Concentration (AUC0-t) | Through 48 hours postdose |
| PK of ARO-MAPT-SC: AUC Versus Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) | Through 48 hours post-dose |
| PK of ARO-MAPT-SC: Apparent Terminal Elimination Half-life (t1/2) | Through 48 hours postdose |
| PK of ARO-MAPT-SC: Apparent Systemic Clearance (CL/F) | Through 48 hours postdose |
| PK of ARO-MAPT-SC: Apparent Terminal-phase Volume of Distribution (Vz/F) | Through 48 hours postdose |
| PK of ARO-MAPT-SC: Amount Excreted (Ae) of Unchanged Drug in Urine From Time Zero to 24 Hours Postdose | Through 24 hours postdose |
| PK of ARO-MAPT-SC: Percentage of Administered Drug Recovered (Fe) in Urine From Time Zero to 24 Hours Postdose | Through 24 hours postdose |
| PK of ARO-MAPT-SC: Renal Clearance (CLR) | Through 24 hours postdose |
| Change from Baseline in Total Protein in Cerebral Spinal Fluid (CSF) Over Time | Baseline through EOS, Day 270 |
| Change from Baseline in Glucose in CSF Over Time | Baseline through EOS, Day 270 |
| Change from Baseline in Cell Count in CSF Over Time | Baseline through EOS, Day 270 |
| Recruiting |
| Toronto |
| Ontario |
| M3B2S7 |
| Canada |
| Research Site 1 | Recruiting | Grafton | Auckland | 1010 | New Zealand |
| D024801 |
| Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |