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NCT Number: NCT06393712

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

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.

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Key information

Conditions

Cerebral Amyloid Angiopathy Amyloidosis Brain Diseases Cardiovascular Diseases Central Nervous System Diseases Cerebral Arterial Diseases Cerebrovascular Disorders Intracranial Arterial Diseases Metabolic Diseases Nervous System Diseases Nutritional and Metabolic Diseases Proteostasis Deficiencies Vascular Diseases

Age range

30 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Clinical Trial Site, Adelaide, Australia

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Placebo

Drug

Placebo will be administered intrathecally

ALN-APP

Drug

ALN-APP will be administered intrathecally

Other names: mivelsiran

Primary outcomes

  1. 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)

    Time frame: Up to 24 months

Secondary outcomes

  1. 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

    Time frame: Up to 24 months

  2. 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

    Time frame: Up to 24 months

  3. Double-blind Treatment Period: Incidence of New Cerebral Hemorrhagic Lesions and White Matter Hyperintensities Assessed on MRI of Brain

    Time frame: Up to 24 months

  4. 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

    Time frame: Up to 24 months

  5. Double-blind Treatment Period: Change from Baseline in Soluble Amyloid Precursor Protein Alpha (sAPPα) Concentration in Cerebrospinal Fluid (CSF)

    Time frame: Up to 24 months

  6. Double-blind Treatment Period: Change from Baseline in Soluble Amyloid Precursor Protein Beta (sAPPβ) Concentration in CSF

    Time frame: Up to 24 months

  7. Double-blind Treatment Period and Open-label Extension (OLE) Period: Frequency of Adverse Events

    Time frame: Up to 48 months

Study contacts

Contact information is provided by the study sponsor or research team.

Alnylam Clinical Trial Information Line

CONTACT

[email protected]

1-877-ALNYLAM

Alnylam Clinical Trial Information Line

CONTACT

[email protected]

1-877-256-9526

Sponsors and collaborators

Lead sponsor

Alnylam Pharmaceuticals

Industry

Registry information

Official study 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)

Acronym: cAPPricorn-1

Important dates

Study start
2024
Primary completion
2027
Study completion
2029
First posted
May 1, 2024
Registry last updated
Jul 15, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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