cAPPricorn-1 - A study to assess the safety and tolerability of ALN-APP in patients with cerebral amyloid angiopathy (CAA)
Summary description of the study
Currently, there are no medications for the treatment of CAA. Physicians are focusing on improving diagnosis, as well as treating and controlling symptoms. In this study, cAPPricorn-1, researchers will test a new investigational drug called ALN-APP. Initial results have shown that it can lower APP levels, which may help prevent the formation of amyloid-beta. This study will investigate the effect of ALN-APP in participants who suffer from either Dutch-type CAA (D-CAA) or sporadic CAA (sCAA).
(BASEC)
Intervention under investigation
The study will be conducted in two parts: the first part is the so-called double-blind phase, which will last 24 months, and the second part is an optional open-label extension phase that will last 18 months. In a double-blind study, neither the participant nor the study physician knows whether the participant is receiving ALN-APP or a placebo that looks like the investigational drug but contains no medication. In the open part of this study, all participants will receive ALN-APP, and they and their doctors will know that they are receiving it.
Patients who meet all study requirements may participate in the study. When a participant enrolls in the study, they will participate in the double-blind phase for up to 24 months, during which they will receive either ALN-APP or placebo. Participants who choose to take part in the open-label extension phase will continue to be treated with ALN-APP for up to 18 months, followed by 12 months of safety monitoring after the last dose. Participants may take part in the study for up to 50 months.
Participants who do not take part in the open-label extension phase will be monitored for safety for 12 months after their last dose in the double-blind phase.
During the study, participants will undergo laboratory tests, imaging studies (e.g., magnetic resonance imaging (MRI)), physical examinations, and cognitive function tests. Researchers will also collect information on adverse events that a participant may experience during the study.
Participants will receive either ALN-APP or placebo via injection in the lower back every 6 months until month 18 in the double-blind phase and every 6 months from month 24 to month 36 in the optional open-label extension phase in the cerebrospinal fluid.
(BASEC)
Disease under investigation
Cerebral amyloid angiopathy (CAA) is a condition that affects the blood vessels in the brain. A protein called amyloid beta accumulates in the walls of the blood vessels and causes damage over time. This can lead to bleeding in the brain, including strokes. Symptoms of CAA may include memory loss and problems with thinking. CAA can also cause sudden episodes of numbness, weakness, and other temporary symptoms. Amyloid beta is the product of a larger protein, the amyloid precursor protein (APP). The cause of amyloid-beta accumulation can vary. In people with Dutch-type CAA, it is caused by a mutation in the APP gene that is passed down within families. In most cases, CAA is sporadic (not inherited) and occurs in older individuals.
(BASEC)
The list is not exhaustive. Patients with sCAA • 50 years or older • Patient is likely to have CAA according to the Boston criteria version 2.0 Patients with D-CAA • 30 years or older • Patient has a known E693Q amyloid precursor protein (APP) gene mutation for Dutch-type CAA (BASEC)
Exclusion criteria
The list is not exhaustive. • Moderate or severe stage of Alzheimer's disease (AD) or significant cognitive impairment (CI) • Patient has previously had a clinical intracerebral hemorrhage (ICH) that occurred less than 90 days prior to the expected randomization into the study • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 times upper limit of normal (ULN) at screening • Estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73 m2 at screening • Patient has recently received an investigational drug • Patient has been treated with an amyloid-targeting antibody (BASEC)
Trial sites
Bern, Geneva
(BASEC)
Sponsor
Alnylam Pharmaceuticals, Inc. IQVIA AG, Branch Basel
(BASEC)
Contact
Contact Person Switzerland
Prof. Dr. med. David Seiffge
+41 31 664 05 09
david.seiffge@clutterinsel.chInselspital Bern, Universitätsklinik für Neurologie
(BASEC)
General Information
Alnylam Pharmaceuticals
1-877-ALNYLAM
clinicaltrials@alnylam.comjennifer.houser@regmarole.com(ICTRP)
Name of the authorising ethics committee (for multicentre studies, only the lead committee)
Ethics Committee Bern
(BASEC)
Date of authorisation
14.11.2024
(BASEC)
ICTRP Trial ID
NCT06393712 (ICTRP)
Official title (approved by ethics committee)
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) (BASEC)
Academic 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) (ICTRP)
Public title
A Phase 2 Trial of ALN-APP in Patients With Cerebral Amyloid Angiopathy (ICTRP)
Disease under investigation
Cerebral Amyloid Angiopathy (ICTRP)
Intervention under investigation
Drug: PlaceboDrug: ALN-APP (ICTRP)
Type of trial
Interventional (ICTRP)
Trial design
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor). (ICTRP)
Inclusion/Exclusion 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) >3upper
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 (ICTRP)
not available
Primary and secondary end points
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) (ICTRP)
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;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;Double-blind Treatment Period: Incidence of New Cerebral Hemorrhagic Lesions and White Matter Hyperintensities Assessed on MRI of Brain;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;Double-blind Treatment Period: Change from Baseline in Soluble Amyloid Precursor Protein Alpha (sAPPa) Concentration in Cerebrospinal Fluid (CSF);Double-blind Treatment Period: Change from Baseline in Soluble Amyloid Precursor Protein Beta (sAPP�) Concentration in CSF;Double-blind Treatment Period and Open-label Extension (OLE) Period: Frequency of Adverse Events (ICTRP)
Registration date
not available
Incorporation of the first participant
not available
Secondary sponsors
not available
Additional contacts
Medical DirectorAlnylam Clinical Trial Information Line, clinicaltrials@alnylam.com, 1-877-ALNYLAM, Alnylam Pharmaceuticals (ICTRP)
Secondary trial IDs
2023-510137-29-00, ALN-APP-002 (ICTRP)
Results-Individual Participant Data (IPD)
not available
Further information on the trial
https://clinicaltrials.gov/study/NCT06393712 (ICTRP)
Results of the trial
Results summary
not available
Link to the results in the primary register
not available