A Phase 2 Trial of ALN-APP in Patients With Cerebral Amyloid Angiopathy
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Placebo, ALN-APP.
- Who it may be relevant to
- Registry conditions: Cerebral Amyloid Angiopathy. Basic parameters: from 30 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States, Australia, Canada, Netherlands, Switzerland +1
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacodynamics of Intrathecally Administered ALN-APP in Patients With Cerebral Amyloid Angiopathy (CAA)
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.
Interventions
- Drug Placebo
Placebo will be administered intrathecally - Drug ALN-APP
ALN-APP will be administered intrathecally
Primary outcome measures
- 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 outcome measures (7)
- 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]
Eligibility criteria
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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Quadruple blind
- Primary purpose
- Treatment
Study locations
United States · 34 centers
- Clinical Trial Site — Los Angeles
- Clinical Trial Site — Orange
- Clinical Trial Site — Palo Alto
- Clinical Trial Site — Sacramento
- Clinical Trial Site — San Francisco
- Clinical Trial Site — Aurora
- Clinical Trial Site — New Haven
- Clinical Trial Site — Gainesville
- … and 26 more centers
Canada · 9 centers
- Clinical Trial Site — Calgary
- Clinical Trial Site — Hamilton
- Clinical Trial Site — Kelowna
- Clinical Trial Site — Moncton
- Clinical Trial Site — Montreal
- Clinical Trial Site — Montreal
- Clinical Trial Site — Ottawa
- Clinical Trial Site — Toronto
- … and 1 more center
Australia · 5 centers
- Clinical Trial Site — Adelaide
- Clinical Trial Site — Brisbane
- Clinical Trial Site — Heidelberg
- Clinical Trial Site — Nedlands
- Clinical Trial Site — Parkville
Netherlands · 3 centers
- Clinical Trial Site — Amsterdam
- Clinical Trial Site — Leiden
- Clinical Trial Site — Nijmegen
Switzerland · 3 centers
- Clinical Trial Site — Bern
- Clinical Trial Site — Geneva
- Clinical Trial Site — Sankt Gallen
United Kingdom · 3 centers
- Clinical Trial Site — Glasgow
- Clinical Trial Site — London
- Clinical Trial Site — London
Identifiers
NCT: NCT06393712 · ALN-APP-002 · 2023-510137-29-00