Cerebral Amyloid Angiopathy
Conditions
Keywords
CAA
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.
Interventions
DRUGPlacebo
Placebo will be administered intrathecally
DRUGALN-APP
ALN-APP will be administered intrathecally
Sponsors
Alnylam Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
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 /
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 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: Incidence of New Cerebral Hemorrhagic Lesions and White Matter Hyperintensities Assessed on MRI of Brain | 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: Change from Baseline in Soluble Amyloid Precursor Protein Beta (sAPPβ) Concentration in CSF | Up to 24 months |
| Double-blind Treatment Period and Open-label Extension (OLE) Period: Frequency of Adverse Events | Up to 48 months |
Countries
Australia, Canada, Netherlands, Switzerland, United Kingdom, United States
Contacts
STUDY_DIRECTORMedical Director
Alnylam Pharmaceuticals
Outcome results
None listed