Senicapoc is a novel intermediate-conductance calcium-activated potassium channel (IKCa3, also known as KCNN4) blocker being evaluated as a potential disease-modifying therapy for Alzheimer's disease. This Phase 2 proof-of-mechanism study is being conducted by the University of California Davis Alzheimer's Disease Research Center to evaluate biological activity and target engagement in patients with mild or prodromal AD.
Trial Details
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Trial Overview
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Senicapoc is a novel intermediate-conductance calcium-activated potassium channel (IKCa3, also known as KCNN4) blocker being evaluated as a potential disease-modifying therapy for Alzheimer's disease. This Phase 2 proof-of-mechanism study is being conducted by the University of California Davis Alzheimer's Disease Research Center to evaluate biological activity and target engagement in patients with mild or prodromal AD.
Trial Details
| Attribute | Value | |-----------|-------| | NCT Number | NCT04804241 | | Phase | Phase 2 | | Sponsor | University of California, Davis | | Collaborators | Alzheimer's Drug Discovery Foundation, Alzheimer's Association, Biossil Inc. | | Status | Recruiting | | Participants | 55 (estimated) | | Study Start Date | March 18, 2022 | | Estimated Completion | June 2026 | | Duration | 52 weeks treatment + 26-week follow-up | | Age Range | 55-85 years | | Diagnosis | Mild or Prodromal Alzheimer's Disease, Amnestic MCI |
Mechanism of Action
IKCa3 (KCNN4) Channel Biology
Senicapoc (also known as TRAM-34) is a potent and selective inhibitor of the intermediate-conductance calcium-activated potassium channel IKCa3 (KCNN4). This channel plays important roles in:
Microglial activation: IKCa3 is expressed in microglia and contributes to pro-inflammatory signaling. Blocking this channel reduces microglial activation and neuroinflammation
Neuroinflammation: The channel is involved in the inflammatory response in the CNS. Inhibition may reduce cytokine production and neuroinflammatory cascades implicated in AD pathogenesis
T-cell function: IKCa3 is important for T-cell activation and proliferation. Modulation may affect immune responses relevant to AD
The therapeutic hypothesis is that IKCa3 blockade will reduce neuroinflammation, a key driver of Alzheimer's disease progression, potentially slowing cognitive decline.
Why Alzheimer's Disease?
Neuroinflammation is increasingly recognized as a central component of Alzheimer's disease pathogenesis. Microglial activation and elevated pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) are found in AD brains and correlate with disease severity. By inhibiting IKCa3, Senicapoc may:
Reduce microglial activation and inflammatory cytokine production
| Location | Status | |----------|--------| | UC Davis Alzheimer's Disease Center, Sacramento, CA | Recruiting | | UC Davis Alzheimer's Disease Center East Bay, Walnut Creek, CA | Recruiting |
Contacts
Principal Investigator: John Olichney, MD (UC Davis)
Site Contact: Martha Forloines, PhD — 916-734-5223 — mrforloines@ucdavis.edu
Clinical Significance
This proof-of-mechanism study is significant for several reasons:
Novel mechanism: IKCa3 blockade represents a different approach from amyloid-targeting therapies
Target engagement: The study includes CSF and serum biomarker measurements to verify biological activity
Disease modification potential: The 78-week total duration (including 26-week post-treatment follow-up) allows assessment of whether effects persist after treatment cessation
Early-stage focus: By targeting mild/prodromal AD, the study addresses a stage where disease-modifying interventions may have the greatest impact
References
[NCT04804241 - Senicapoc in Alzheimer's Disease](https://clinicaltrials.gov/study/NCT04804241)
[UC Davis Alzheimer's Disease Research Center](https://health.ucdavis.edu/alzheimers/)
[Study Information - UC Davis](https://studypages.com/s/a-study-of-senicapoc-in-alzheimers-disease-763405/)