A Phase 2 Trial of ALN-APP in Patients With Cerebral Amyloid Angiopathy

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

  • Cerebral Amyloid Angiopathy

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