NCT05231785

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, pharmacodynamics (PD) and pharmacokinetics (PK) of a single dose and multiple doses of ALN-APP administered by intrathecal (IT) injection in adult patients with early-onset Alzheimer's Disease (EOAD). Maximum treatment duration for Part A: single dose. Maximum treatment duration for Part B: 12 months.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
60

participants targeted

Target at P75+ for phase_1

Timeline
36mo left

Started Feb 2022

Longer than P75 for phase_1

Geographic Reach
4 countries

8 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress59%
Feb 2022Apr 2029

First Submitted

Initial submission to the registry

January 30, 2022

Completed
5 days until next milestone

Study Start

First participant enrolled

February 4, 2022

Completed
5 days until next milestone

First Posted

Study publicly available on registry

February 9, 2022

Completed
7.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 20, 2029

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 20, 2029

Last Updated

May 4, 2026

Status Verified

April 1, 2026

Enrollment Period

7.2 years

First QC Date

January 30, 2022

Last Update Submit

April 30, 2026

Conditions

Early-Onset Alzheimer Disease

Keywords

EOAD

Outcome Measures

Primary Outcomes (2)

  • Part A: Frequency of Adverse Events

    Up to 12 months

  • Part B: Frequency of Adverse Events

    Up to 24 months

Secondary Outcomes (5)

  • Part A and Part B: Change from Baseline in Levels of Cerebrospinal Fluid (CSF) Soluble Amyloid Precursor Protein Alpha (sAPPα) and Soluble Amyloid Precursor Protein Beta (sAPPβ)

    Part A up to 12 months; Part B up to 24 months

  • Part A and Part B: Area Under the Plasma Concentration-time Curve (AUC) of ALN-APP and of Potential Metabolites

    Part A up to 12 months; Part B up to 24 months

  • Part A and Part B: Maximum Observed Plasma Concentration (Cmax) of ALN-APP and of Potential Metabolites

    Part A up to 12 months; Part B up to 24 months

  • Part A: Fraction of ALN-APP and Potential Metabolites Excreted in the Urine (fe)

    Up to 1 day

  • Part A and Part B: Concentration of ALN-APP and Potential Metabolites at Time 't' (Ct) in Plasma and CSF

    Part A up to 12 months; Part B up to 24 months

Study Arms (3)

Part A: ALN-APP

EXPERIMENTAL

Participants will be administered a single dose of ALN-APP.

Drug: ALN-APP

Part A: Placebo

PLACEBO COMPARATOR

Participants will be administered a single dose of placebo.

Drug: Placebo

Part B:

EXPERIMENTAL

Participants will be administered multiple doses of ALN-APP.

Drug: ALN-APP

Interventions

ALN-APPDRUG

ALN-APP will be administered intrathecally (IT)

Also known as: mivelsiran
Part A: ALN-APPPart B:
PlaceboDRUG

Placebo will be administered IT

Part A: Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Has mild cognitive impairment or mild dementia due to EOAD
  • Has Clinical Dementia Rating (CDR) global score 0.5 or 1.0 and Mini Mental State Examination (MMSE) \>20

You may not qualify if:

  • Has Non-Alzheimer's disease dementia
  • Has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>2×upper limit of normal (ULN)
  • Has estimated glomerular filtration rate (eGFR) \<45 mL/min/1.73m\^2 at Screening
  • Has recently received an investigational agent
  • Has recent treatment with amyloid-targeting antibody

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (8)

Clinical Trial Site

La Jolla, California, 92037, United States

COMPLETED

Clinical Trial Site

Indianapolis, Indiana, 46202, United States

RECRUITING

Clinical Trial Site

Montreal, H3A 2B4, Canada

RECRUITING

Clinical Trial Site

Toronto, M3B 2S7, Canada

RECRUITING

Clinical Trial Site

Amsterdam, 1081 BT, Netherlands

RECRUITING

Clinical Trial Site

Groningen, 9713 GG, Netherlands

COMPLETED

Clinical Trial Site

Huntley Street, WC1E 6AG, United Kingdom

RECRUITING

Clinical Trial Site

Sheffield, S10 2JF, United Kingdom

RECRUITING

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

DementiaBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesTauopathiesNeurodegenerative DiseasesNeurocognitive DisordersMental Disorders

Study Officials

  • Medical Director

    Alnylam Pharmaceuticals

    STUDY DIRECTOR

Central Study Contacts

Alnylam Clinical Trial Information Line

CONTACT

1-877-ALNYLAMclinicaltrials@alnylam.com

Alnylam Clinical Trial Information Line

CONTACT

1-877-256-9526clinicaltrials@alnylam.com

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 30, 2022

First Posted

February 9, 2022

Study Start

February 4, 2022

Primary Completion (Estimated)

April 20, 2029

Study Completion (Estimated)

April 20, 2029

Last Updated

May 4, 2026

Record last verified: 2026-04

Data Sharing

IPD Sharing
Will not share

Locations

US(2)CA(2)NL(2)GB(2)