A Phase 2 Trial of ALN-APP in Patients With Cerebral Amyloid Angiopathy
cAPPricorn-1
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)
2 other identifiers
interventional
200
6 countries
57
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started May 2024
Longer than P75 for phase_2
57 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 19, 2024
CompletedFirst Posted
Study publicly available on registry
May 1, 2024
CompletedStudy Start
First participant enrolled
May 17, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 9, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 14, 2029
April 24, 2026
April 1, 2026
3.2 years
April 19, 2024
April 23, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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 Outcomes (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
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
- +2 more secondary outcomes
Study Arms (2)
ALN-APP
EXPERIMENTALParticipants will be administered multiple doses of ALN-APP during the double-blind treatment period and optional open-label extension period.
Placebo/ALN-APP
PLACEBO COMPARATORParticipants 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.
Interventions
Eligibility Criteria
You may qualify if:
- Is 50 years or older
- Has probable CAA per the Boston Criteria Version 2.0
- Is 30 years or older
- Has known E693Q amyloid precursor protein (APP) gene mutation for Dutch-type CAA
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (57)
Clinical Trial Site
Los Angeles, California, 90095, United States
Clinical Trial Site
Orange, California, 92868, United States
Clinical Trial Site
Palo Alto, California, 94304, United States
Clinical Trial Site
Sacramento, California, 95816, United States
Clinical Trial Site
San Francisco, California, 94114, United States
Clinical Trial Site
Aurora, Colorado, 80045, United States
Clinical Trial Site
New Haven, Connecticut, 06510, United States
Clinical Trial Site
Gainesville, Florida, 32608, United States
Clinical Trial Site
Jacksonville, Florida, 32224, United States
Clinical Trial Site
Maitland, Florida, 32751, United States
Clinical Trial Site
Naples, Florida, 34105, United States
Clinical Trial Site
Chicago, Illinois, 60612, United States
Clinical Trial Site
Lexington, Kentucky, 40504, United States
Clinical Trial Site
New Orleans, Louisiana, 70121, United States
Clinical Trial Site
Boston, Massachusetts, 02114, United States
Clinical Trial Site
Plymouth, Massachusetts, 02360, United States
Clinical Trial Site
Rochester, Minnesota, 55905, United States
Clinical Trial Site
St Louis, Missouri, 63110, United States
Clinical Trial Site
Hackensack, New Jersey, 07601, United States
Clinical Trial Site
New York, New York, 10016, United States
Clinical Trial Site
New York, New York, 10029, United States
Clinical Trial Site
New York, New York, 10032, United States
Clinical Trial Site
New York, New York, 10065, United States
Clinical Trial Site
Durham, North Carolina, 27705, United States
Clinical Trial Site
Canton, Ohio, 44718, United States
Clinical Trial Site
Cleveland, Ohio, 44195, United States
Clinical Trial Site
Abington, Pennsylvania, 19001, United States
Clinical Trial Site
Philadelphia, Pennsylvania, 19104, United States
Clinical Trial Site
Pittsburgh, Pennsylvania, 15213, United States
Clinical Trial Site
Dallas, Texas, 75243, United States
Clinical Trial Site
Dallas, Texas, 75390, United States
Clinical Trial Site
Houston, Texas, 77030, United States
Clinical Trial Site
San Antonio, Texas, 78229, United States
Clinical Trial Site
Seattle, Washington, 98104, United States
Clinical Trial Site
Adelaide, 5000, Australia
Clinical Trial Site
Brisbane, 4029, Australia
Clinical Trial Site
Heidelberg, 3084, Australia
Clinical Trial Site
Nedlands, 6009, Australia
Clinical Trial Site
Parkville, 3050, Australia
Clinical Trial Site
Calgary, T2N 4Z6, Canada
Clinical Trial Site
Hamilton, L8L 2X2, Canada
Clinical Trial Site
Kelowna, V1Y 1Z9, Canada
Clinical Trial Site
Moncton, E1C 2Z3, Canada
Clinical Trial Site
Montreal, H3A 2B4, Canada
Clinical Trial Site
Montreal, H3G 1H9, Canada
Clinical Trial Site
Ottawa, K1Z 1G3, Canada
Clinical Trial Site
Toronto, M3B 2S7, Canada
Clinical Trial Site
Victoria, V8R 1J8, Canada
Clinical Trial Site
Amsterdam, 1081 GN, Netherlands
Clinical Trial Site
Leiden, 2333ZA, Netherlands
Clinical Trial Site
Nijmegen, 6525 GA, Netherlands
Clinical Trial Site
Bern, 3010, Switzerland
Clinical Trial Site
Geneva, 1205, Switzerland
Clinical Trial Site
Sankt Gallen, 9007, Switzerland
Clinical Trial Site
Glasgow, G51 4TF, United Kingdom
Clinical Trial Site
London, SE5 8AF, United Kingdom
Clinical Trial Site
London, WC1N 3BG, United Kingdom
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Medical Director
Alnylam Pharmaceuticals
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 19, 2024
First Posted
May 1, 2024
Study Start
May 17, 2024
Primary Completion (Estimated)
August 9, 2027
Study Completion (Estimated)
December 14, 2029
Last Updated
April 24, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
Access to Anonymized individual participant data that support these results is made available 12 months after study completion and not less than 12 months after the product and indication have been approved in the US and/or the EU. Access to data may be declined where there is likelihood a patient could be identified or other feasibility issue, where there is a potential conflict of interest, a planned business activities or an actual or potential competitive risk. Data will be provided contingent upon the approval of a research proposal and the execution of a data sharing agreement. Timeframes for data access may vary and can take up to 6 months or more. Requests for access to data can be submitted via the website www.vivli.org. Questions can also be directed to datasharing@alnylam.com.