Cerebral Amyloid AngiopathyPhase 2cAPPricorn-1NCT06393712
A Phase 2 Trial of ALN-APP in Patients With Cerebral Amyloid Angiopathy
A Phase 2 study testing ALN-APP in people with Cerebral Amyloid Angiopathy, run by Alnylam Pharmaceuticals at 57 sites in 6 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 30 years and older
- Conditions the study is for
- Cerebral Amyloid Angiopathy
- What is being tested?
- ALN-APP
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 210 participants
- Where
- 57 sitesin 6 countries
- Study dates
- 17 May 2024to 14 Dec 2029
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
57 sites in 6 countries.
57 sites in 6 countries
United States34 sites
Clinical Trial Site
Abington, Pennsylvania, 19001
Clinical Trial Site
Aurora, Colorado, 80045
Clinical Trial Site
Boston, Massachusetts, 02114
Clinical Trial Site
Canton, Ohio, 44718
Clinical Trial Site
Chicago, Illinois, 60612
Clinical Trial Site
Cleveland, Ohio, 44195
Clinical Trial Site
Dallas, Texas, 75243
Clinical Trial Site
Dallas, Texas, 75390
Clinical Trial Site
Durham, North Carolina, 27705
Clinical Trial Site
Gainesville, Florida, 32608
Clinical Trial Site
Hackensack, New Jersey, 07601
Clinical Trial Site
Houston, Texas, 77030
Clinical Trial Site
Jacksonville, Florida, 32224
Clinical Trial Site
Lexington, Kentucky, 40504
Clinical Trial Site
Los Angeles, California, 90095
Clinical Trial Site
Maitland, Florida, 32751
Clinical Trial Site
Naples, Florida, 34105
Clinical Trial Site
New Haven, Connecticut, 06510
Clinical Trial Site
New Orleans, Louisiana, 70121
Clinical Trial Site
New York, New York, 10016
Clinical Trial Site
New York, New York, 10029
Clinical Trial Site
New York, New York, 10032
Clinical Trial Site
New York, New York, 10065
Clinical Trial Site
Orange, California, 92868
Clinical Trial Site
Palo Alto, California, 94304
Clinical Trial Site
Philadelphia, Pennsylvania, 19104
Clinical Trial Site
Pittsburgh, Pennsylvania, 15213
Clinical Trial Site
Plymouth, Massachusetts, 02360
Clinical Trial Site
Rochester, Minnesota, 55905
Clinical Trial Site
Sacramento, California, 95816
Clinical Trial Site
San Antonio, Texas, 78229
Clinical Trial Site
San Francisco, California, 94114
Clinical Trial Site
Seattle, Washington, 98104
Clinical Trial Site
St Louis, Missouri, 63110
Canada9 sites
Clinical Trial Site
Calgary, T2N 4Z6
Clinical Trial Site
Hamilton, L8L 2X2
Clinical Trial Site
Kelowna, V1Y 1Z9
Clinical Trial Site
Moncton, E1C 2Z3
Clinical Trial Site
Montreal, H3A 2B4
Clinical Trial Site
Montreal, H3G 1H9
Clinical Trial Site
Ottawa, K1Z 1G3
Clinical Trial Site
Toronto, M3B 2S7
Clinical Trial Site
Victoria, V8R 1J8
Australia5 sites
Clinical Trial Site
Adelaide, 5000
Clinical Trial Site
Brisbane, 4029
Clinical Trial Site
Heidelberg, 3084
Clinical Trial Site
Nedlands, 6009
Clinical Trial Site
Parkville, 3050
Netherlands3 sites
Clinical Trial Site
Amsterdam, 1081 GN
Clinical Trial Site
Leiden, 2333ZA
Clinical Trial Site
Nijmegen, 6525 GA
Switzerland3 sites
Clinical Trial Site
Bern, 3010
Clinical Trial Site
Geneva, 1205
Clinical Trial Site
Sankt Gallen, 9007
United Kingdom3 sites
Clinical Trial Site
Glasgow, G51 4TF
Clinical Trial Site
London, SE5 8AF
Clinical Trial Site
London, WC1N 3BG
About this study
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)
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.
- Conditions
- Cerebral Amyloid Angiopathy
- Being tested
- Placebo, ALN-APP
- Keywords
- CAA
- Medical subject headings
- Cerebral Amyloid Angiopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Placebo will be administered intrathecally
ALN-APPDrug
Also called mivelsiran
ALN-APP will be administered intrathecally
| Study group | Role | What they receive |
|---|---|---|
| ALN-APP | Experimental | Participants will be administered multiple doses of ALN-APP during the double-blind treatment period and optional open-label extension period. Receives: Drug: ALN-APP |
| Placebo/ALN-APP | Placebo comparator | 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. Receives: Drug: Placebo; Drug: ALN-APP |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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
Measured: 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
Measured: Up to 24 months
Double-blind Treatment Period: Incidence of New Cerebral Hemorrhagic Lesions and White Matter Hyperintensities Assessed on MRI of Brain
Measured: 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
Measured: Up to 24 months
Double-blind Treatment Period: Change from Baseline in Soluble Amyloid Precursor Protein Alpha (sAPPα) Concentration in Cerebrospinal Fluid (CSF)
Measured: Up to 24 months
Double-blind Treatment Period: Change from Baseline in Soluble Amyloid Precursor Protein Beta (sAPPβ) Concentration in CSF
Measured: Up to 24 months
Double-blind Treatment Period and Open-label Extension (OLE) Period: Frequency of Adverse Events
Measured: Up to 48 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2024
- Study start17 May 2024
- Primary completion9 Aug 2027 (estimated)
- Study completion14 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cerebral Amyloid AngiopathyStudies of the same condition, open and under way.
- More trials run by Alnylam PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 210 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alnylam Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Alnylam Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06393712
- Sponsor's protocol ID
- ALN-APP-002
- Other IDs
- 2023-510137-29-00, 2023
- Acronym
- cAPPricorn-1
- Status last verified
- Oct 2026
- First submitted
- 19 Apr 2024
- Last updated
- 20 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.