A Phase 2 Trial of ALN-APP in Patients With Cerebral Amyloid Angiopathy
- Registration Number
- NCT06393712
- Lead Sponsor
- Alnylam Pharmaceuticals
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 200
Inclusion Criteria
Not provided
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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo/ALN-APP Placebo 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. ALN-APP ALN-APP Participants will be administered multiple doses of ALN-APP during the double-blind treatment period and optional open-label extension period. Placebo/ALN-APP 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.
- Primary Outcome Measures
Name Time Method 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) Up to 24 months
- Secondary Outcome Measures
Name Time Method 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 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 Up to 24 months Double-blind Treatment Period: Change from Baseline in Soluble Amyloid Precursor Protein Alpha (sAPPα) Concentration in Cerebrospinal Fluid (CSF) Up to 24 months 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 Up to 24 months Double-blind Treatment Period: Change from Baseline in Soluble Amyloid Precursor Protein Beta (sAPPβ) Concentration in CSF Up to 24 months Double-blind Treatment Period: Incidence of New Cerebral Hemorrhagic Lesions and White Matter Hyperintensities Assessed on MRI of Brain Up to 24 months Double-blind Treatment Period and Open-label Extension (OLE) Period: Frequency of Adverse Events Up to 48 months
Trial Locations
- Locations (1)
Clinical Trial Site
🇬🇧London, United Kingdom