Trial ID: [NCT06808984](https://clinicaltrials.gov/study/NCT06808984)
Sponsor: Celgene (Bristol Myers Squibb)
Status: Recruiting
Phase: Phase 2
Participants: 120
Overview
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BMS-986368 is a Phase 2 clinical trial conducted by Celgene (Bristol Myers Squibb) investigating a novel therapeutic approach for agitation in Alzheimer's disease. The trial is currently recruiting participants, representing Celgene/BMS's continued investment in neuropsychiatric symptoms of dementia.
...Trial ID: [NCT06808984](https://clinicaltrials.gov/study/NCT06808984)
Sponsor: Celgene (Bristol Myers Squibb)
Status: Recruiting
Phase: Phase 2
Participants: 120
Overview
Mermaid diagram (expand to render)
BMS-986368 is a Phase 2 clinical trial conducted by Celgene (Bristol Myers Squibb) investigating a novel therapeutic approach for agitation in Alzheimer's disease. The trial is currently recruiting participants, representing Celgene/BMS's continued investment in neuropsychiatric symptoms of dementia.
Agitation is one of the most common and challenging behavioral and psychological symptoms of dementia (BPSD), affecting up to 70% of patients during the disease course["@cerejeira2012"]. It encompasses a spectrum of behaviors including restlessness, aggression, disinhibition, and pacing that significantly impact quality of life for both patients and caregivers.
Trial Design
| Parameter | Value |
|-----------|-------|
| Phase | Phase 2 |
| Status | Recruiting |
| Enrollment | 120 participants |
| Sponsor | Celgene (Bristol Myers Squibb) |
| Condition | Agitation in Alzheimer's Disease |
| Study Type | Interventional |
| Allocation | Randomized |
Mechanism of Action
While the specific molecular mechanism of BMS-986368 has not been publicly disclosed, the therapeutic approach likely targets one or more of the key pathways implicated in Alzheimer's-related agitation:
Neuroinflammation Hypothesis
Neuroinflammation is increasingly recognized as a central contributor to behavioral symptoms in Alzheimer's disease. Key mechanisms include:
- Microglial activation: Chronic microglial activation produces pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) that can alter neuronal function and contribute to behavioral changes
- Cytokine effects on neurotransmission: Inflammatory cytokines can modulate dopamine, serotonin, and glutamate signaling in brain regions involved in emotional regulation
- Blood-brain barrier permeability: Neuroinflammation may increase BBB permeability, allowing peripheral inflammatory signals to affect CNS function
Neurotransmitter Modulation
Agitation in AD involves dysregulation of multiple neurotransmitter systems:
- Dopamine: Involved in motivational behavior and response to environmental stimuli. Dopaminergic dysfunction may contribute to apathy and agitation
- Serotonin: Critical for mood regulation and impulse control. Serotonergic deficits are associated with irritability and aggression
- GABA: The primary inhibitory neurotransmitter. GABAergic dysfunction may lead to disinhibition and excess motor activity
- Noradrenaline: Involved in arousal and attention. Locus coeruleus degeneration in AD may contribute to attentional deficits and agitation
Novel CNS Targets
Celgene/BMS has historically focused on innovative approaches to CNS disorders:
- Epigenetic modifiers: Histone deacetylase (HDAC) inhibitors and other chromatin-modifying enzymes
- Cell cycle regulators: Compounds targeting aberrant cell cycle re-entry in neurons
- RNA splicing modulators: Agents targeting alternative splicing events implicated in neurodegeneration
- Immunomodulatory approaches: Novel anti-inflammatory strategies for neuroprotection
Background
Burden of Agitation in Alzheimer's Disease
Agitation represents one of the most significant unmet needs in Alzheimer's disease management[@lyketsos2011]:
- Prevalence: Affects 40-70% of Alzheimer's patients during the disease course
- Impact on caregivers: Agitation is the primary driver of caregiver burnout and institutionalization
- Economic burden: Associated with $10,000-15,000 annually in excess healthcare costs per patient
- Treatment challenges: Current pharmacoptions have limited efficacy and significant side effect profiles
Current Treatment Landscape
| Treatment | Limitations |
|-----------|-------------|
| Atypical antipsychotics | Increased mortality, stroke, cognitive decline |
| Typical antipsychotics | Extrapyramidal symptoms, TD risk |
| Benzodiazepines | Falls, cognitive worsening, dependence |
| Mood stabilizers | Variable efficacy, toxicity concerns |
| Non-pharmacological | Limited efficacy in moderate-severe agitation |
This therapeutic gap underscores the need for novel agents like BMS-986368 that target underlying disease mechanisms rather than simply suppressing symptoms[@geda2013].
Clinical Development
Celgene/BMS Neuroscience Program
Celgene (acquired by Bristol Myers Squibb in 2019) has a robust neuroscience research program focusing on:
- Neurodegenerative diseases: Alzheimer's, Parkinson's, ALS, multiple sclerosis
- Neuropsychiatric disorders: Depression, anxiety, schizophrenia
- Pain: Chronic pain conditions including neuropathic pain
Key areas of investigation include:
- Inflammatory and immune mechanisms in CNS disorders
- Novel small molecule approaches to modulate neural function
- Cell-based therapies for neurological conditions
Drug Development Pipeline
BMS-986368 represents one of several CNS candidates in the Celgene/BMS pipeline:
| Compound | Target | Indication | Stage |
|----------|--------|------------|-------|
| BMS-986368 | undisclosed | AD Agitation | Phase 2 |
| Various | HDAC | Neurodegeneration | Preclinical |
| Multiple | Immune modulators | MS, ALS | Various |
Study Endpoints
While specific endpoints are detailed on ClinicalTrials.gov, Phase 2 trials typically evaluate:
Primary Endpoints
- Safety and tolerability
- Dose-limiting toxicities
- Maximum tolerated dose
Secondary Endpoints
- Preliminary efficacy signals using validated agitation scales
- Pharmacokinetic parameters
- Target engagement biomarkers
Assessment Instruments
Commonly used measures for agitation trials include:
- Cohen-Mansfield Agitation Inventory (CMAI): Gold standard for agitation measurement
- Neuropsychiatric Inventory (NPI): Assesses behavioral symptoms including agitation
- ADAS-Cog: Cognitive function assessment
- CGI-C: Clinical Global Impression of Change
Safety Considerations
Given the patient population, special safety considerations include:
- Cardiovascular monitoring: Elderly patients with AD are at increased CV risk
- Cognitive effects: Assessment of any worsening of cognition
- Fall risk: Monitor for increased sedation or orthostatic changes
- Drug interactions: Many AD patients take multiple concomitant medications
- Mortality surveillance: Increased awareness following FDA black box warnings for antipsychotics in dementia
Clinical Significance
The development of BMS-986368 is significant for several reasons:
Novel mechanism: Represents a potentially new approach to treating agitation beyond existing neurotransmitter-targeting drugs
Disease modification potential: May address underlying causes of agitation rather than just symptoms
Unmet need: Agitation remains one of the most difficult-to-treat symptoms in AD
Pipeline diversification: Expands Celgene/BMS CNS portfolio beyond oncology rootsRelated Pages
- [Agitation in Alzheimer's Disease](/diseases/alzheimers-disease)
- [Behavioral and Psychological Symptoms of Dementia](/mechanisms/bpsd-neurobiology)
- [Neuroinflammation in Alzheimer's Disease](/mechanisms/neuroinflammation-alzheimers)
- [Other Agitation Trials](/clinical-trials/?tag=agitation)
- [Celgene/BMS Pipeline](/clinical-trials/drug-pipeline)
External Links
- [ClinicalTrials.gov: NCT06808984](https://clinicaltrials.gov/study/NCT06808984)
- [BMS Research & Development Pipeline](https://www.bms.com/research-and-development/pipeline.html)
- [Celgene (BMS) Neuroscience](https://www.bms.com/research-and-development.html)
References
[Cerejeira J, Lagarto L, Mukaetova-Ladinska EB, Behavioral and psychological symptoms of dementia (2012)](https://pubmed.ncbi.nlm.nih.gov/22586428/)
[Lyketsos CG, Carrillo MC, Ryan JM, et al, Neuropsychiatric symptoms in Alzheimer's disease (2011)](https://doi.org/10.1016/j.jalz.2011.01.003)
[Geda YE, Schneider LS, Gitlin LN, et al, Neuropsychiatric symptoms in Alzheimer's disease (2013)](https://doi.org/10.1038/mp.2013.96)
[Celgene/BMS Neuroscience Pipeline](https://www.bms.com/research-and-development/pipeline.html)