Executive Summary
flowchart TD
clinical_trials_nct07212062_x_["X/T + X-EC + Lecanemab Phase 2 NCT07212062 Alzh"]
clinical_trials_nct07212062_x_["Executive"]
clinical_trials_nct07212062_x_ -->|"related to"| clinical_trials_nct07212062_x_
style clinical_trials_nct07212062_x_ fill:#81c784,stroke:#333,color:#000
clinical_trials_nct07212062_x_["Summary"]
clinical_trials_nct07212062_x_ -->|"related to"| clinical_trials_nct07212062_x_
style clinical_trials_nct07212062_x_ fill:#81c784,stroke:#333,color:#000
clinical_trials_nct07212062_x_["Phase"]
clinical_trials_nct07212062_x_ -->|"related to"| clinical_trials_nct07212062_x_
style clinical_trials_nct07212062_x_ fill:#81c784,stroke:#333,color:#000
clinical_trials_nct07212062_x_["trial"]
clinical_trials_nct07212062_x_ -->|"related to"| clinical_trials_nct07212062_x_
style clinical_trials_nct07212062_x_ fill:#81c784,stroke:#333,color:#000
style clinical_trials_nct07212062_x_ fill:#4fc3f7,stroke:#333,color:#000
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.
...Executive Summary
Mermaid diagram (expand to render)
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["@karxt_mechanism"]. 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["@lecanemab_clarity"].
Trial Overview
| 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) |
Study Design
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:
- Arm A (Active): Xanomeline and Trospium Chloride Capsules + Lecanemab 10 mg/kg IV every 2 weeks
- Arm B (Placebo): Placebo capsules + Lecanemab 10 mg/kg IV every 2 weeks
The quadruple-blind design means that participants, investigators, care providers, and outcome assessors are all blinded to treatment assignment.
Mechanism Rationale
Lecanemab (Anti-Amyloid Therapy)
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[@lecanemab_clarity]. By targeting protofibrils, Lecanemab reduces amyloid plaque burden in the brain, which is hypothesized to slow disease progression.
Xanomeline (Muscarinic Agonist)
Xanomeline is a selective M1 and M4 muscarinic acetylcholine receptor agonist. Cholinergic signaling through these receptors is critical for learning, memory, and attention[@muscarinic_adrenergic]. In Alzheimer's disease, cholinergic neurons are lost, leading to cognitive deficits. M1 agonists like xanomeline can:
- Enhance postsynaptic cholinergic signaling
- Improve cognitive function through hippocampal and cortical circuits
- Potentially reduce amyloid processing via M1 receptor activation
Why Combination Therapy?
The rationale for combining Lecanemab with Xanomeline includes:
Complementary Mechanisms: Lecanemab addresses the upstream amyloid pathology while Xanomeline enhances downstream cholinergic signaling
Symptomatic + Disease-Modifying: Combining a disease-modifying antibody with a symptomatic cognitive enhancer
Proven Safety Profile: Both compounds have established safety profiles in separate trials
Rationale for Continuing Lecanemab: Participants continue receiving Lecanemab throughout the trial to maintain amyloid clearance while adding cognitive enhancementEligibility Criteria
Inclusion Requirements
- Age 60–85 years
- Confirmed Alzheimer's disease diagnosis meeting NIA-AA criteria
- Currently receiving Lecanemab treatment (completed ≥14 infusions)
- Mini-Mental State Examination (MMSE) score of 16–24 (mild to moderate dementia)
- Body Mass Index (BMI) 18–35 kg/m²
- Has a reliable caregiver/study partner with ≥10 hours/week contact
- Stable dose of permitted AD medications (if applicable) for ≥12 weeks
Exclusion Criteria
- History of suicidal behavior or active psychiatric disorders
- Significant cardiovascular, pulmonary, renal, or hepatic disease
- History of stroke within 12 months
- Cerebral amyloid angiopathy (CAA)
- Epilepsy or history of seizures
- Central nervous system neoplasm
- Pregnancy or breastfeeding
- Prior exposure to Xanomeline/Trospium (X/T)
- Apolipoprotein E (ApoE) e4 homozygotes (increased risk of ARIA)
Outcomes
Primary Outcome
Safety and Tolerability (through Week 28):
- Incidence of adverse events (AEs)
- Incidence of serious adverse events (SAEs)
- Discontinuation rates due to AEs
- Amyloid-related imaging abnormalities (ARIA) on MRI
Secondary Outcome
Efficacy:
- Quality of Life in Alzheimer's Disease (QoL-AD) score change from Baseline to Week 24
Investigational Products
| 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:
- Phone: 561-487-1027
- Email: CostellResearch@fcneurology.net
Number of Sites: 3 United States locations (specific locations not publicly listed)
Clinical Significance
This trial represents an important step in Alzheimer's disease therapeutic development:
First Combination Trial: This appears to be one of the first trials combining an anti-amyloid antibody with a muscarinic agonist
Building on Established Frameworks: Uses participants already on Lecanemab, minimizing risk by maintaining disease-modifying therapy
Dual-Target Approach: Addresses both amyloid pathology and cholinergic dysfunction simultaneouslyIf successful, this combination approach could establish a new paradigm for AD treatment, demonstrating that combining disease-modifying and symptomatic therapies can provide enhanced benefits.
Related Pages
- [Lecanemab](/entities/lecanemab)
- [Lecanemab Clarity AD](/clinical-trials/lecanemab-clarity-ad)
- [Combination Therapy for Neurodegeneration](/therapeutics/combination-therapy-neurodegeneration)
- [Muscarinic Receptor Signaling in AD](/mechanisms/gpcr-signaling)
- [Alzheimer's Disease Clinical Trials](/clinical-trials/alzheimers-disease)
Pathway Diagram
The following diagram shows the key molecular relationships involving X/T + X-EC + Lecanemab Phase 2 (NCT07212062) — Alzheimer's Disease discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)