ALN-APP for Cerebral Amyloid Angiopathy

(cAPPricorn-1 Trial)

Recruiting at 47 trial locations

Overseen By Alnylam Clinical Trial Information Line

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Alnylam Pharmaceuticals

Must not be taking: Amyloid antibodies

Disqualifiers: Alzheimer's, Cognitive impairment, ICH, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ALN-APP for individuals with cerebral amyloid angiopathy (CAA), a condition where protein deposits affect brain blood vessels. The trial aims to assess how ALN-APP impacts CAA progression and to ensure its safety and tolerability for patients. Participants will receive either ALN-APP or a placebo (a substance with no active drug) during a double-blind period and can later opt to continue with ALN-APP in an open-label extension. Individuals with sporadic or Dutch-type CAA who have had the condition for some time might be suitable for this study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have recently received an investigational agent or have been treated with an amyloid-targeting antibody, you may not be eligible to participate.

Is there any evidence suggesting that ALN-APP is likely to be safe for humans?

Studies have shown that ALN-APP has been generally well-tolerated in early testing for Alzheimer's disease and cerebral amyloid angiopathy (CAA). In earlier research, patients received gradually increasing doses of ALN-APP. These studies found the treatment safe, with no serious side effects linked to the drug. The most common side effects were mild, such as headache and nausea. These findings suggest that ALN-APP may be safe for further testing in people with CAA. However, as this treatment remains under study, ongoing research will continue to assess its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for CAA?

Researchers are excited about ALN-APP for Cerebral Amyloid Angiopathy because it represents a novel approach to treating this condition. Unlike standard treatments that primarily manage symptoms, ALN-APP targets the root cause by interfering with amyloid protein production in the brain. This treatment uses RNA interference technology, a cutting-edge mechanism that reduces the production of amyloid precursor protein, which could potentially slow disease progression. This innovative method offers hope for more effective management of the disease compared to current options.

What evidence suggests that ALN-APP might be an effective treatment for cerebral amyloid angiopathy?

Research has shown that ALN-APP, which participants in this trial may receive, has shown promise in early trials for conditions like cerebral amyloid angiopathy (CAA) and Alzheimer's disease. Interim results from earlier studies suggest it may help reduce amyloid-beta, a protein that accumulates in the brain and is linked to these diseases. Lowering amyloid-beta could slow the progression of CAA, which affects blood vessels in the brain. Although more data from ongoing studies is needed, ALN-APP targets a key factor in CAA's development, offering hope for those affected by this condition. ^{1 2 3 6 7}

Who Is on the Research Team?

Medical Director

Principal Investigator

Alnylam Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for adults aged 50 or older with probable Cerebral Amyloid Angiopathy (CAA) as per Boston Criteria, or those 30 and above with a known E693Q amyloid precursor protein gene mutation linked to Dutch-type CAA. It's not suitable for individuals who don't meet these specific conditions.

Inclusion Criteria

I have been diagnosed with cerebral amyloid angiopathy according to the Boston Criteria.

I am 50 years old or older.

I am 30 years old or older.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive multiple doses of ALN-APP or placebo during the double-blind treatment period

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-6 months

Open-label extension (optional)

Participants may opt into continuation of treatment with ALN-APP long-term

18 months

What Are the Treatments Tested in This Trial?

Interventions

• ALN-APP

Trial Overview The study tests the effects of ALN-APP on slowing down CAA disease progression compared to a placebo. Participants will be randomly assigned to receive either ALN-APP or placebo over a period of up to 50 months, including an optional extension phase.

How Is the Trial Designed?

Group I: ALN-APP Experimental Treatment 1 Intervention

Participants will be administered multiple doses of ALN-APP during the double-blind treatment period and optional open-label extension period.

Group II: Placebo/ALN-APP Placebo Group 2 Interventions

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.

Who Is Running the Clinical Trial?

Alnylam Pharmaceuticals

Lead Sponsor

Trials

81

Recruited

16,100+

Dr. Yvonne Greenstreet

Alnylam Pharmaceuticals

Chief Executive Officer since 2021

MD from the University of Leeds, MBA from INSEAD

Dr. Pushkal Garg

Alnylam Pharmaceuticals

Chief Medical Officer since 2016

MD from Columbia University

Published Research Related to This Trial

In a study of 14 patients with cerebral amyloid angiopathy (CAA) related inflammation, MRI scans showed specific patterns of T2-hyperintense lesions that correlated with clinical symptoms, indicating the importance of imaging in diagnosis and monitoring.

The presence of the APOE epsilon4/epsilon4 genotype was found in 76.9% of patients with CAA-related inflammation, suggesting a strong genetic link that could influence treatment strategies and risk assessment for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Course of cerebral amyloid angiopathy-related inflammation. Kinnecom, C., Lev, MH., Wendell, L., et al.[2016]

Cerebral amyloid angiopathy (CAA) is linked to Alzheimer's disease and can lead to serious issues like intracerebral hemorrhage and cognitive impairment, particularly affecting elderly patients.

This case series highlights that CAA can present with atypical dementia syndromes, such as logopenic variant primary progressive aphasia and normal pressure hydrocephalus, complicating its diagnosis and emphasizing the need for careful evaluation in patients with dementia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atypical Clinical Manifestations of Cerebral Amyloid Angiopathy. Akers, C., Acosta, LMY., Considine, C., et al.[2020]

Cerebral amyloid angiopathy (CAA) is a significant cause of intracerebral hemorrhage and cognitive decline in older adults, characterized by specific brain lesions and diagnostic criteria that have led to increased detection of the disease.

At a biological level, CAA is linked to a failure in protein elimination, which exacerbates amyloid-β accumulation and vascular injury, highlighting the need for further research into potential treatments and interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging concepts in sporadic cerebral amyloid angiopathy. Charidimou, A., Boulouis, G., Gurol, ME., et al.[2022]

Cerebral amyloid angiopathy associated with inflammation is a significant condition in older adults, often presenting with cognitive decline, seizures, and headaches, and is characterized by an inflammatory response to β-amyloid deposits in the brain.

A systematic review identified 213 pathologically proven cases, highlighting the need for improved diagnostic criteria and treatment strategies, as current management options are limited and the condition can be challenging to diagnose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerebral amyloid angiopathy associated with inflammation: A systematic review of clinical and imaging features and outcome. Corovic, A., Kelly, S., Markus, HS.[2019]

Cerebral amyloid angiopathy (CAA) can lead to serious neurological issues like seizures and strokes due to inflammation caused by amyloid buildup in blood vessels, and its inflammatory subtypes (CAA-related inflammation and amyloid-beta-related angiitis) are part of a spectrum of central nervous system vasculopathies.

As treatments for Alzheimer's disease evolve towards anti-amyloid therapies, the recognition of inflammatory CAA is expected to rise, highlighting the importance of awareness and diagnosis, which may now be achieved without invasive procedures in some cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inflammatory Cerebral Amyloid Angiopathy: A Broad Clinical Spectrum. de Souza, A., Tasker, K.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06393712

NCT06393712 | A Phase 2 Trial of ALN-APP in Patients ... 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, ...

2. investors.alnylam.com investors.alnylam.com/press-release?id=27761

Alnylam Pharmaceuticals Press Release | Oct 25, 2023 Alnylam reports additional positive interim Phase 1 results for ALN-APP, in development for Alzheimer's disease and cerebral amyloid angiopathy.

3. mayo.edu mayo.edu/research/clinical-trials/cls-20575115

A Phase 2 Trial of ALN-APP in Patients With Cerebral ... 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 ...

4. neurologylive.com neurologylive.com/view/phase-2-cappricorn-study-assess-rna-therapeutic-mivelsiran-cerebral-amyloid-angiopathy

Phase 2 cAPPricorn Study to Assess RNA Therapeutic ... The cAPPricorn-1 Phase 2 trial will assess mivelsiran's efficacy in CAA, focusing on reducing the annualized rate of new cerebral microbleeds over 24 months.

5. frontiersin.org frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2025.1632252/full

Cerebral amyloid angiopathy: a narrative review Cerebral amyloid angiopathy (CAA) is a cerebrovascular disorder characterized by the accumulation of amyloid-beta (Aβ) in the walls of cerebral vessels.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12479547/

Cerebral amyloid angiopathy: a narrative review - PMC Cerebral amyloid angiopathy (CAA) is a common cerebrovascular disorder characterized by the deposition and accumulation of amyloid-beta (Aβ) ...

7. alz-journals.onlinelibrary.wiley.com alz-journals.onlinelibrary.wiley.com/doi/abs/10.1002/alz.084521

Single ascending dose results from an ongoing Phase 1 study ... We report additional safety, pharmacodynamic, and biomarker data from the double-blind, placebo-controlled, single ascending dose part of the ...