Alzheimer Disease, Alzheimer Disease, Early Onset
Conditions
Brief summary
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.
Interventions
DRUGARO-MAPT-SC
• single or multiple doses of ARO-MAPT-SC by subcutaneous (SC) injection
DRUGPlacebo
• calculated volume to match active treatment by SC administration
Sponsors
Arrowhead Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
(All Participants): * Body mass index between 18.0 and 35.0 kilograms (kg)/square meter (m\^2) at Screening * Not pregnant or breast-feeding * Able and willing to provide written informed consent prior to the performance of any study specific procedures * Participants of childbearing potential must agree to use highly effective contraception in addition to a condom during the study and for at least 90 days following the end of the study or last dose of study drug, whichever is later; participants must not donate sperm or eggs during the study and for at least 90 days following the end of the study or last dose of study drug whichever is later 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): * Blood pressure outside of specified range in the protocol * Human immunodeficiency virus (HIV) infection (seropositive at Screening) * Seropositive for hepatitis B (HBV) or hepatitis C (HCV) at Screening * Intellectual disability or significant behavioral neuropsychiatric manifestation * Clinically significant cardiac, liver, or renal disease * Any contraindications to lumbar puncture * Known allergy or possible allergy to either ARO-MAPT-SC or to its excipients Note: Additional inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants with Treatment-Emergent Adverse Events (TEAEs) Over Time | Through End of Study (EOS), Day 270 |
Secondary
| Measure | 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 |
| 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 |
Countries
Canada, New Zealand
Contacts
CONTACTMedical Monitor
Outcome results
None listed