ALN-APP for Cerebral Amyloid Angiopathy
(cAPPricorn-1 Trial)
Recruiting in Palo Alto (17 mi)
+11 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Alnylam Pharmaceuticals
Must not be taking: Amyloid antibodies
Disqualifiers: Alzheimer's, Cognitive impairment, ICH, others
Prior Safety Data
Trial Summary
What is the purpose of this trial?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.
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.
How is the drug ALN-APP different from other treatments for cerebral amyloid angiopathy?
ALN-APP is unique because it targets the underlying cause of cerebral amyloid angiopathy by potentially reducing the accumulation of amyloid-beta in the brain's blood vessels, whereas other treatments primarily address symptoms or complications like inflammation or bleeding.
12345Eligibility Criteria
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.
+1 more
Trial Timeline
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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: ALN-APPExperimental Treatment1 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-APPPlacebo Group2 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Clinical Trial SiteNew York, NY
Clinical Trial SitePlymouth, MA
Clinical Trial SiteAbington, PA
Clinical Trial SiteOttawa, Canada
More Trial Locations
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Who Is Running the Clinical Trial?
Alnylam PharmaceuticalsLead Sponsor
References
Cerebral amyloid angiopathy associated with inflammation: A systematic review of clinical and imaging features and outcome. [2019]Background Cerebral amyloid angiopathy associated with inflammation is an increasingly recognized condition, characterized by an inflammatory response to the vascular deposits of β-amyloid within the brain that are the hallmark of cerebral amyloid angiopathy. Two main patterns of this inflammatory response have been identified to date: one involving a perivascular inflammatory cell infiltrate (cerebral amyloid angiopathy-related inflammation); the other a transmural vasculitic process (A-beta related angiitis). Unlike cerebral amyloid angiopathy itself, which predisposes to intracerebral hemorrhage and has no known treatment, cerebral amyloid angiopathy associated with inflammation typically presents in diverse ways and diagnosis may be challenging and delayed. Aims We sought to summarize the clinical features, imaging appearances and available data on outcome and treatment responses, using information derived from a systematic review of pathologically proven cases of cerebral amyloid angiopathy associated with inflammation. Summary of review We identified 213 distinct pathologically proven cases of cerebral amyloid angiopathy-related inflammation/A-beta related angiitis, from 104 publications. The clinical presentation, imaging features, pathology, treatment, and outcomes of cerebral amyloid angiopathy associated with inflammation are described. Conclusions Cerebral amyloid angiopathy associated with inflammation is an important and increasingly recognized clinical condition, which affects the older patient population and presents most commonly with cognitive decline, seizures, and headaches. Future research is required to develop and validate diagnostic criteria and determine optimum treatment strategies.
Inflammatory Cerebral Amyloid Angiopathy: A Broad Clinical Spectrum. [2023]Cerebral amyloid angiopathy (CAA) is a common central nervous system (CNS) vasculopathy, which in some cases is associated with subacute encephalopathy, seizures, headaches, or strokes due to vascular inflammation directed against vascular amyloid accumulation. The pathological subtypes of inflammatory CAA include CAA-related inflammation (CAAri) with mostly perivascular lymphocytic infiltrates, or amyloid-beta (Aβ)-related angiitis (ABRA) with transmural granulomatous inflammation. CAAri and ABRA probably represent part of the spectrum of CNS vasculopathies, intermediate between CAA and primary CNS vasculitis, and they are closely related to Aβ-related imaging abnormalities and other manifestations of an inflammatory response directed against Aβ in the leptomeninges and cerebral parenchyma. As treatment strategies in Alzheimer's disease shift toward potentially effective antiamyloid immunotherapy, the incidence rate of inflammatory CAA (which is probably an underrecognized condition) is likely to increase. Its clinical features are varied and include subacute encephalopathy, behavioral symptoms, headaches, seizures, and focal neurological deficits, which necessitate a high degree of suspicion for this disorder that often responds to treatment. The recent definition of the typical clinical and radiological syndrome has increased its recognition and may eliminate the need for invasive histological sampling in at least some affected patients. Here we review the pathophysiology, clinical spectrum, and approach to diagnosis, and discuss illustrative cases that highlight the wide range of clinical presentations.
Course of cerebral amyloid angiopathy-related inflammation. [2016]A subset of patients with cerebral amyloid angiopathy (CAA) present with cognitive symptoms, seizures, headaches, T2-hyperintense MRI lesions, and neuropathologic evidence of CAA-associated vascular inflammation.
Atypical Clinical Manifestations of Cerebral Amyloid Angiopathy. [2020]Cerebral amyloid angiopathy is a vasculopathy caused by β-amyloid deposition in cerebral arterioles and capillaries. It is closely linked to Alzheimer's disease and predisposes elderly patients to intracerebral hemorrhage, transient focal neurological episodes, and cognitive impairment. Because of a predilection for symptomatic hemorrhage, particularly in the frontal lobes, cerebral amyloid angiopathy may also cause a dysexecutive syndrome.
Emerging concepts in sporadic cerebral amyloid angiopathy. [2022]Sporadic cerebral amyloid angiopathy is a common, well-defined small vessel disease and a largely untreatable cause of intracerebral haemorrhage and contributor to age-related cognitive decline. The term 'cerebral amyloid angiopathy' now encompasses not only a specific cerebrovascular pathological finding, but also different clinical syndromes (both acute and progressive), brain parenchymal lesions seen on neuroimaging and a set of diagnostic criteria-the Boston criteria, which have resulted in increasingly detected disease during life. Over the past few years, it has become clear that, at the pathophysiological level, cerebral amyloid angiopathy appears to be in part a protein elimination failure angiopathy and that this dysfunction is a feed-forward process, which potentially leads to worsening vascular amyloid-β accumulation, activation of vascular injury pathways and impaired vascular physiology. From a clinical standpoint, cerebral amyloid angiopathy is characterized by individual focal lesions (microbleeds, cortical superficial siderosis, microinfarcts) and large-scale alterations (white matter hyperintensities, structural connectivity, cortical thickness), both cortical and subcortical. This review provides an interdisciplinary critical outlook on various emerging and changing concepts in the field, illustrating mechanisms associated with amyloid cerebrovascular pathology and neurological dysfunction.