Clinical trial NCT06393712: A Phase 2 Trial of ALN-APP in Patients With Cerebral Amyloid Angiopathy
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Cerebral Amyloid Angiopathy
Keywords: CAA
Lead sponsor: Alnylam Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2024-05-01
Enrollment: 200
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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)
timeFrame: Up to 24 months
Secondary outcomes:
measure: 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
timeFrame: Up to 24 months
measure: 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
timeFrame: Up to 24 months
measure: Double-blind Treatment Period: Incidence of New Cerebral Hemorrhagic Lesions and White Matter Hyperintensities Assessed on MRI of Brain
timeFrame: Up to 24 months
measure: 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
timeFrame: Up to 24 months
measure: Double-blind Treatment Period: Change from Baseline in Soluble Amyloid Precursor Protein Alpha (sAPPα) Concentration in Cerebrospinal Fluid (CSF)
timeFrame: Up to 24 months
measure: Double-blind Treatment Period: Change from Baseline in Soluble Amyloid Precursor Protein Beta (sAPPβ) Concentration in CSF
timeFrame: Up to 24 months
measure: Double-blind Treatment Period and Open-label Extension (OLE) Period: Frequency of Adverse Events
timeFrame: Up to 48 months
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: Clinical Trial Site
state: California
city: San Francisco
country: United States
facility: Clinical Trial Site
state: California
city: Jacksonville
country: United States
facility: Clinical Trial Site
state: Florida
city: Maitland
country: United States
facility: Clinical Trial Site
state: Florida
city: Naples
country: United States
facility: Clinical Trial Site
state: Florida
city: Lexington
country: United States
facility: Clinical Trial Site
state: Kentucky
city: New Orleans
country: United States
facility: Clinical Trial Site
state: Louisiana
city: Boston
country: United States
facility: Clinical Trial Site
state: Massachusetts
city: Plymouth
country: United States
facility: Clinical Trial Site
state: Massachusetts
city: Rochester
country: United States
facility: Clinical Trial Site
state: Minnesota
city: Saint Louis
country: United States
facility: Clinical Trial Site
state: Missouri
city: New York
country: United States
facility: Clinical Trial Site
state: New York
city: New York
country: United States
facility: Clinical Trial Site
state: New York
city: New York
country: United States
facility: Clinical Trial Site
state: New York
city: Canton
country: United States
facility: Clinical Trial Site
state: Ohio
city: Cleveland
country: United States
facility: Clinical Trial Site
state: Ohio
city: Abington
country: United States
facility: Clinical Trial Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Clinical Trial Site
state: Pennsylvania
city: Dallas
country: United States
facility: Clinical Trial Site
state: Texas
city: Houston
country: United States
facility: Clinical Trial Site
state: Texas
city: Heidelberg
country: Australia
facility: Clinical Trial Site
city: Herston
country: Australia
facility: Clinical Trial Site
city: Nedlands
country: Australia
facility: Clinical Trial Site
city: Parkville
country: Australia
facility: Clinical Trial Site
city: Calgary
country: Canada
facility: Clinical Trial Site
state: Alberta
city: Richmond
country: Canada
facility: Clinical Trial Site
state: British Columbia
city: Moncton
country: Canada
facility: Clinical Trial Site
state: New Brunswick
city: Hamilton
country: Canada
facility: Clinical Trial Site
state: Ontario
city: Ottawa
country: Canada
facility: Clinical Trial Site
state: Ontario
city: Toronto
country: Canada
facility: Clinical Trial Site
state: Ontario
city: Richmond
country: Canada
facility: Clinical Trial Site
city: Amsterdam
country: Netherlands
facility: Clinical Trial Site
city: Leiden
country: Netherlands
facility: Clinical Trial Site
city: Nijmegen
country: Netherlands
facility: Clinical Trial Site
city: Bern
country: Switzerland
facility: Clinical Trial Site
city: Geneve
country: Switzerland
facility: Clinical Trial Site
city: Denmark Hill
country: United Kingdom
facility: Clinical Trial Site
city: Glasgow
country: United Kingdom
facility: Clinical Trial Site
city: London
country: United Kingdom
facility: Clinical Trial Site
Study officials:
affiliation: Alnylam Pharmaceuticals
name: Medical Director
role: STUDY_DIRECTOR
References: