A Phase 2 Trial of ALN-APP in Patients With Cerebral Amyloid Angiopathy (cAPPricorn-1)

May 12, 2026 updated by: Alnylam Pharmaceuticals

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)

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 Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

200

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Australia
      • Adelaide, Australia, 5000
        • Recruiting
        • Clinical Trial Site
      • Brisbane, Australia, 4029
        • Recruiting
        • Clinical Trial Site
      • Heidelberg, Australia, 3084
        • Recruiting
        • Clinical Trial Site
      • Nedlands, Australia, 6009
        • Recruiting
        • Clinical Trial Site
      • Parkville, Australia, 3050
        • Recruiting
        • Clinical Trial Site
  • Canada
      • Calgary, Canada, T2N 4Z6
        • Recruiting
        • Clinical Trial Site
      • Hamilton, Canada, L8L 2X2
        • Recruiting
        • Clinical Trial Site
      • Kelowna, Canada, V1Y 1Z9
        • Recruiting
        • Clinical Trial Site
      • Moncton, Canada, E1C 2Z3
        • Recruiting
        • Clinical Trial Site
      • Montreal, Canada, H3G 1H9
        • Recruiting
        • Clinical Trial Site
      • Montreal, Canada, H3A 2B4
        • Recruiting
        • Clinical Trial Site
      • Ottawa, Canada, K1Z 1G3
        • Recruiting
        • Clinical Trial Site
      • Toronto, Canada, M3B 2S7
        • Recruiting
        • Clinical Trial Site
      • Victoria, Canada, V8R 1J8
        • Recruiting
        • Clinical Trial Site
  • Netherlands
      • Amsterdam, Netherlands, 1081 GN
        • Recruiting
        • Clinical Trial Site
      • Leiden, Netherlands, 2333ZA
        • Recruiting
        • Clinical Trial Site
      • Nijmegen, Netherlands, 6525 GA
        • Recruiting
        • Clinical Trial Site
  • Switzerland
      • Bern, Switzerland, 3010
        • Recruiting
        • Clinical Trial Site
      • Geneva, Switzerland, 1205
        • Recruiting
        • Clinical Trial Site
      • Sankt Gallen, Switzerland, 9007
        • Terminated
        • Clinical Trial Site
  • United Kingdom
      • Glasgow, United Kingdom, G51 4TF
        • Recruiting
        • Clinical Trial Site
      • London, United Kingdom, SE5 8AF
        • Active, not recruiting
        • Clinical Trial Site
      • London, United Kingdom, WC1N 3BG
        • Active, not recruiting
        • Clinical Trial Site
  • United States
    • California
      • Los Angeles, California, United States, 90095
        • Active, not recruiting
        • Clinical Trial Site
      • Orange, California, United States, 92868
        • Active, not recruiting
        • Clinical Trial Site
      • Palo Alto, California, United States, 94304
        • Active, not recruiting
        • Clinical Trial Site
      • Sacramento, California, United States, 95816
        • Active, not recruiting
        • Clinical Trial Site
      • San Francisco, California, United States, 94114
        • Active, not recruiting
        • Clinical Trial Site
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Active, not recruiting
        • Clinical Trial Site
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Active, not recruiting
        • Clinical Trial Site
    • Florida
      • Gainesville, Florida, United States, 32608
        • Active, not recruiting
        • Clinical Trial Site
      • Jacksonville, Florida, United States, 32224
        • Active, not recruiting
        • Clinical Trial Site
      • Maitland, Florida, United States, 32751
        • Active, not recruiting
        • Clinical Trial Site
      • Naples, Florida, United States, 34105
        • Active, not recruiting
        • Clinical Trial Site
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Active, not recruiting
        • Clinical Trial Site
    • Kentucky
      • Lexington, Kentucky, United States, 40504
        • Active, not recruiting
        • Clinical Trial Site
    • Louisiana
      • New Orleans, Louisiana, United States, 70121
        • Active, not recruiting
        • Clinical Trial Site
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Active, not recruiting
        • Clinical Trial Site
      • Plymouth, Massachusetts, United States, 02360
        • Active, not recruiting
        • Clinical Trial Site
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Active, not recruiting
        • Clinical Trial Site
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Active, not recruiting
        • Clinical Trial Site
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Active, not recruiting
        • Clinical Trial Site
    • New York
      • New York, New York, United States, 10032
        • Active, not recruiting
        • Clinical Trial Site
      • New York, New York, United States, 10065
        • Active, not recruiting
        • Clinical Trial Site
      • New York, New York, United States, 10016
        • Active, not recruiting
        • Clinical Trial Site
      • New York, New York, United States, 10029
        • Active, not recruiting
        • Clinical Trial Site
    • North Carolina
      • Durham, North Carolina, United States, 27705
        • Active, not recruiting
        • Clinical Trial Site
    • Ohio
      • Canton, Ohio, United States, 44718
        • Active, not recruiting
        • Clinical Trial Site
      • Cleveland, Ohio, United States, 44195
        • Active, not recruiting
        • Clinical Trial Site
    • Pennsylvania
      • Abington, Pennsylvania, United States, 19001
        • Active, not recruiting
        • Clinical Trial Site
      • Philadelphia, Pennsylvania, United States, 19104
        • Active, not recruiting
        • Clinical Trial Site
      • Pittsburgh, Pennsylvania, United States, 15213
        • Active, not recruiting
        • Clinical Trial Site
    • Texas
      • Dallas, Texas, United States, 75390
        • Active, not recruiting
        • Clinical Trial Site
      • Dallas, Texas, United States, 75243
        • Active, not recruiting
        • Clinical Trial Site
      • Houston, Texas, United States, 77030
        • Active, not recruiting
        • Clinical Trial Site
      • San Antonio, Texas, United States, 78229
        • Active, not recruiting
        • Clinical Trial Site
    • Washington
      • Seattle, Washington, United States, 98104
        • Active, not recruiting
        • Clinical Trial Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ALN-APP
Participants will be administered multiple doses of ALN-APP during the double-blind treatment period and optional open-label extension period.
Drug: ALN-APP
ALN-APP will be administered intrathecally
Other Names:
  • mivelsiran
Placebo Comparator: Placebo/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.
Drug: ALN-APP
ALN-APP will be administered intrathecally
Other Names:
  • mivelsiran
Drug: Placebo
Placebo will be administered intrathecally

What is the study measuring?

Primary Outcome Measures

Outcome 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)
Time Frame: Up to 24 months
Up to 24 months

Secondary Outcome Measures

Outcome 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
Time Frame: Up to 24 months
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
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
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
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
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
Up to 24 months
Double-blind Treatment Period and Open-label Extension (OLE) Period: Frequency of Adverse Events
Time Frame: Up to 48 months
Up to 48 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alnylam Pharmaceuticals

Investigators

  • Study Director: Medical Director, Alnylam Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 17, 2024

Primary Completion (Estimated)

August 9, 2027

Study Completion (Estimated)

December 14, 2029

Study Registration Dates

First Submitted

April 19, 2024

First Submitted That Met QC Criteria

April 26, 2024

First Posted (Actual)

May 1, 2024

Study Record Updates

Last Update Posted (Actual)

May 14, 2026

Last Update Submitted That Met QC Criteria

May 12, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ALN-APP-002
  • 2023-510137-29-00 (Ctis)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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