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

Phase 2RecruitingNCT06393712

Alnylam Pharmaceuticals200 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

200

Conditions

Cerebral Amyloid Angiopathy

Interventions

Placebo

Eligibility

Sex: ALLMin age: 30 Years

Medical Language ↔ Plain English

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

Locations (57)

Clinical Trial Site

Los Angeles, California, United States

ACTIVE_NOT_RECRUITING

Clinical Trial Site

Orange, California, United States

ACTIVE_NOT_RECRUITING

Clinical Trial Site

Palo Alto, California, United States

ACTIVE_NOT_RECRUITING

Clinical Trial Site

Sacramento, California, United States

ACTIVE_NOT_RECRUITING

Outcomes

Primary Outcomes

Double-blind Treatment Period: Annualized Rate of New Lobar Cerebral Microbleeds (CMBs) Assessed on Magnetic Resonance Imaging (MRI) of Brain in Patients with Sporadic Cerebral Amyloid Angiopathy (sCAA)

Time frame: Up to 24 months

Secondary Outcomes

Double-blind Treatment Period: Global Rank Based on Severity, Count, Symptom Burden, and Timing of New Clinical Hemorrhagic Events and Hemorrhagic Lesions Assessed on MRI of Brain

Time frame: Up to 24 months

Double-blind Treatment Period: Change from Baseline Over Time in Cerebrovascular Vasoreactivity Measured by Blood Oxygenation Level Dependent (BOLD) Parameters with Visual-evoked Functional MRI

Time frame: Up to 24 months

Double-blind Treatment Period: Incidence of New Cerebral Hemorrhagic Lesions and White Matter Hyperintensities Assessed on MRI of Brain

Time frame: Up to 24 months

Double-blind Treatment Period: Change from Baseline Over Time in the Total Cerebral Amyloid Angiopathy (CAA) Small Vessel Disease Score Assessed on MRI of Brain

Time frame: Up to 24 months

Double-blind Treatment Period: Change from Baseline in Soluble Amyloid Precursor Protein Alpha (sAPPα) Concentration in Cerebrospinal Fluid (CSF)

Time frame: Up to 24 months

Double-blind Treatment Period: Change from Baseline in Soluble Amyloid Precursor Protein Beta (sAPPβ) Concentration in CSF

Time frame: Up to 24 months

Double-blind Treatment Period and Open-label Extension (OLE) Period: Frequency of Adverse Events

Time frame: Up to 48 months

Central Contacts

Alnylam Clinical Trial Information Line

CONTACT

1-877-ALNYLAM clinicaltrials@alnylam.com

Alnylam Clinical Trial Information Line

CONTACT

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