Purpose

The purpose of the study is to evaluate the effect of ALN-APP on measures of CAA disease progression and to characterize the safety, tolerability, and pharmacodynamics (PD) of ALN-APP in adult patients with sporadic CAA (sCAA) and Dutch-type CAA (D-CAA). The study will be conducted over 2 periods: a 24-month double-blind treatment period and an optional 18-month open-label extension (OLE) period. The estimated duration of study participation, inclusive of screening, treatment, and additional safety follow-up, is up to 50 months.

Condition

Eligibility

Eligible Ages
Over 30 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

(sporadic CAA patients): - Is 50 years or older - Has probable CAA per the Boston Criteria Version 2.0 Inclusion Criteria (Dutch-type CAA patients): - Is 30 years or older - Has known E693Q amyloid precursor protein (APP) gene mutation for Dutch-type CAA

Exclusion Criteria

  • Moderate or severe stage Alzheimer's disease (AD) or significant cognitive impairment (CI) - Has a history of previous clinical intracerebral hemorrhage (ICH) with onset less than 90 days prior to anticipated randomization in the study - Has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3×upper limit of normal (ULN) at Screening - Has estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m^2 at Screening - Has recently received an investigational agent - Has had treatment with amyloid-targeting antibody Note: other protocol defined inclusion / exclusion criteria apply

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
ALN-APP
Participants will be administered multiple doses of ALN-APP during the double-blind treatment period and optional open-label extension period.
  • Drug: Placebo
    Placebo will be administered intrathecally
  • Drug: ALN-APP
    ALN-APP will be administered intrathecally
    Other names:
    • mivelsiran
Placebo Comparator
Placebo/ALN-APP
Participants will be administered multiple doses of placebo during the double-blind treatment period. Participants who continue into the optional open-label extension period will be administered multiple doses of ALN-APP.
  • Drug: Placebo
    Placebo will be administered intrathecally
  • Drug: ALN-APP
    ALN-APP will be administered intrathecally
    Other names:
    • mivelsiran

Recruiting Locations

More Details

NCT ID
NCT06393712
Status
Recruiting
Sponsor
Alnylam Pharmaceuticals

Study Contact

Alnylam Clinical Trial Information Line
1-877-ALNYLAM
clinicaltrials@alnylam.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.