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

Cerebral Amyloid Angiopathy Clinical Trial

— cAPPricorn-1  

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06393712
• Other study ID #: ALN-APP-002
• Secondary ID: 2023-510137-29-0
• Status: Recruiting
• Phase: Phase 2
• Start date: May 2024
• Est. completion date: November 2029

Study information

• Verified date: May 2024
• Source: Alnylam Pharmaceuticals
• Contact: Alnylam Clinical Trial Information Line
• Phone: 1-877-ALNYLAM
• Email: clinicaltrials[@]alnylam.com
• Is FDA regulated: No
• Study type: Interventional

Clinical 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). 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: November 2029
• Est. primary completion date: July 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Amyloidosis
• Cerebral Amyloid Angiopathy

Intervention

Drug:
• Placebo
Placebo will be administered intrathecally
• ALN-APP
ALN-APP will be administered intrathecally

Locations

Country	Name	City	State
Canada	Clinical Trial Site	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Alnylam Pharmaceuticals

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)		Up to 24 months
Secondary	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		Up to 24 months
Secondary	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		Up to 24 months
Secondary	Double-blind Treatment Period: Incidence of New Cerebral Hemorrhagic Lesions and White Matter Hyperintensities Assessed on MRI of Brain		Up to 24 months
Secondary	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		Up to 24 months
Secondary	Double-blind Treatment Period: Change from Baseline in Soluble Amyloid Precursor Protein Alpha (sAPPa) Concentration in Cerebrospinal Fluid (CSF)		Up to 24 months
Secondary	Double-blind Treatment Period: Change from Baseline in Soluble Amyloid Precursor Protein Beta (sAPPß) Concentration in CSF		Up to 24 months
Secondary	Double-blind Treatment Period and Open-label Extension (OLE) Period: Frequency of Adverse Events		Up to 48 months