This Phase 2 clinical trial evaluates the safety and tolerability of combining xanomeline and trospium (X/T) with Lecanemab in participants with Alzheimer's disease who are currently receiving Lecanemab monotherapy. The trial represents a novel combination therapy approach, pairing an existing anti-amyloid antibody with a muscarinic receptor agonist to potentially enhance cognitive benefits through complementary mechanisms.
Xanomeline is a selective M1/M4 muscarinic acetylcholine receptor agonist that has demonstrated cognitive benefits in previous trials[1]. Trospium chloride is a muscarinic antagonist that does not cross the blood-brain barrier, used to reduce peripheral cholinergic side effects. Lecanemab (BAN2401) is an anti-amyloid-beta protofibril antibody that has shown efficacy in clearing amyloid plaques and slowing cognitive decline in the Clarity AD trial[2].
| Parameter | Value |
|---|---|
| NCT Number | NCT07212062 |
| Trial Title | A Phase II, Randomized, Double-Blind, Placebo Controlled Study to Evaluate the Safety and Tolerability of X/T+X-EC vs. Placebo in Participants With Alzheimer's Disease Currently Treated With Lecanemab |
| Phase | Phase 2 |
| Status | Not Yet Recruiting |
| Enrollment | 60 participants |
| Sponsor | Neurology Office of South Florida |
| Collaborator | Bristol-Myers Squibb |
| Study Type | Interventional |
| Design | Randomized, Parallel Group, Quadruple-Blind |
| Start Date | December 1, 2025 (Estimated) |
| End Date | April 1, 2028 (Estimated) |
This is a quadruple-blind, placebo-controlled, randomized trial evaluating the safety and tolerability of adding Xanomeline/Trospium (X/T) to existing Lecanemab therapy. Participants currently receiving Lecanemab will be randomized to receive either:
The quadruple-blind design means that participants, investigators, care providers, and outcome assessors are all blinded to treatment assignment.
Lecanemab is a humanized IgG1 monoclonal antibody that selectively binds to amyloid-beta (Aβ) protofibrils, the soluble oligomeric forms of Aβ believed to be more neurotoxic than plaques[2:1]. By targeting protofibrils, Lecanemab reduces amyloid plaque burden in the brain, which is hypothesized to slow disease progression.
Xanomeline is a selective M1 and M4 muscarinic acetylcholine receptor agonist. Cholinergic signaling through these receptors is critical for learning, memory, and attention[3]. In Alzheimer's disease, cholinergic neurons are lost, leading to cognitive deficits. M1 agonists like xanomeline can:
The rationale for combining Lecanemab with Xanomeline includes:
Safety and Tolerability (through Week 28):
Efficacy:
| Product | Description | Dose |
|---|---|---|
| Xanomeline | Selective M1/M4 muscarinic receptor agonist | Oral capsules, dose escalation protocol |
| Trospium Chloride | Peripheral muscarinic antagonist (reduces peripheral side effects) | Oral capsules |
| Lecanemab | Anti-Aβ protofibril antibody | 10 mg/kg IV every 2 weeks |
Principal Investigator: Brian Costell, MD
Institution: Neurology Office of South Florida
Contact:
Number of Sites: 3 United States locations (specific locations not publicly listed)
This trial represents an important step in Alzheimer's disease therapeutic development:
If successful, this combination approach could establish a new paradigm for AD treatment, demonstrating that combining disease-modifying and symptomatic therapies can provide enhanced benefits.
Kaur, G., et al. Xanomeline-Trospium (KARXT): a novel muscarinic receptor agonist for schizophrenia. Journal of Medicinal Chemistry. 2023. ↩︎
van Dyck, C.H., et al. Lecanemab in Early Alzheimer's Disease. The New England Journal of Medicine. 2023. ↩︎ ↩︎
Gray, J.A., et al. Muscarinic receptor agonists as therapeutic targets in Alzheimer's disease. Neuropharmacology. 2023. ↩︎