Study of ARO-MAPT-SC in Healthy Subjects and Subjects With Early Alzheimer's Disease

A Phase 1/2a Placebo-Controlled Dose-Escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ARO-MAPT-SC in Healthy Subjects and Subjects With Early Alzheimer's Disease

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.

Study Overview

• Status: Recruiting
• Conditions: Alzheimer Disease; Alzheimer Disease, Early Onset
• Intervention / Treatment: Drug: ARO-MAPT-SC; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 112
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Medical Monitor; Phone Number: 626-304-3400; Email: AROMAPT-SC-1001@arrowheadpharma.com

Study Locations

• Canada
  • Ontario
    • East York, Ontario, Canada, M4G 3E8
      • Recruiting
      • Research Site 3
    • Toronto, Ontario, Canada, M3B2S7
      • Recruiting
      • Research Site 2
• New Zealand
  • Auckland
    • Grafton, Auckland, New Zealand, 1010
      • Recruiting
      • Research Site 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria (All Participants):

• Body mass index between 18.0 and 35.0 kg/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
• On stable doses of AD-related medications for at least 8 weeks prior to Screening Visit and throughout the Screening period until Day 1
• 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/exclusion criteria may apply per protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ARO-MAPT-SC; ARO-MAPT-SC injection	Drug: ARO-MAPT-SC; • single or multiple doses of ARO-MAPT-SC by subcutaneous (SC) injection
Placebo Comparator: Placebo; Sterile normal saline (0.9%)	Drug: Placebo; • calculated volume to match active treatment by SC administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants with Treatment-Emergent Adverse Events (TEAEs) Over Time	Through End of Study (EOS), Day 270

Secondary Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: Arrowhead Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: October 23, 2025
• First Submitted That Met QC Criteria: October 23, 2025
• First Posted (Actual): October 27, 2025

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Alzheimer Disease
• Other Study ID Numbers: AROMAPT-SC-1001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No