BMS-986446 (also known as ruvaprisutide or BOS-986) is a monoclonal antibody targeting the microtubule binding region (MTBR) of tau protein. This Phase 2 clinical trial (NCT06268886) evaluates the safety, tolerability, and efficacy of BMS-986446 in patients with early Alzheimer's disease (AD). The trial is sponsored by Bristol Myers Squibb (BMS) and represents a key component of their tau-targeted therapeutic program for AD.
Trial Details
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Overview
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BMS-986446 (also known as ruvaprisutide or BOS-986) is a monoclonal antibody targeting the microtubule binding region (MTBR) of tau protein. This Phase 2 clinical trial (NCT06268886) evaluates the safety, tolerability, and efficacy of BMS-986446 in patients with early Alzheimer's disease (AD). The trial is sponsored by Bristol Myers Squibb (BMS) and represents a key component of their tau-targeted therapeutic program for AD.
Trial Details
| Parameter | Value | |-----------|-------| | NCT Number | NCT06268886 | | Official Title | A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of BMS-986446 in Subjects With Early Alzheimer's Disease | | Sponsor | Bristol Myers Squibb | | Phase | Phase 2 | | Status | Recruiting | | Study Type | Interventional | | Allocation | Randomized | | Intervention Model | Parallel Assignment | | Masking | Double Blind (Participant, Investigator) | | Enrollment | 475 participants (planned) |
Study Population
Inclusion Criteria
Age 55-85 years
Clinical diagnosis of early Alzheimer's disease (MCI due to AD or mild AD dementia)
MMSE score ≥ 20
Positive amyloid biomarker (CSF or PET)
Tau biomarker positivity (elevated p-tau in CSF)
Stable AD medications (if applicable)
Exclusion Criteria
History of other neurodegenerative diseases
Significant cerebrovascular disease
Active psychiatric disorders
Contraindications to MRI or PET imaging
Mechanism of Action
BMS-986446 is an anti-MTBR tau antibody that specifically binds to the microtubule binding region of tau protein, which is the core domain involved in tau aggregation. Unlike N-terminal or mid-domain tau antibodies, anti-MTBR antibodies are designed to:
Block cell-to-cell propagation: Bind to extracellular tau aggregates and prevent their uptake by neighboring neurons
Promote clearance: Engage the immune system to clear tau aggregates via Fc-mediated mechanisms
Prevent seeding: Neutralize tau seeds that initiate aggregation in recipient cells
The MTBR-targeting approach is supported by evidence that this region is critical for tau aggregation and is present in multiple tau species including monomers, oligomers, and fibrils.
Study Design
Randomization (1:1:1:1) ├── Placebo (n=~118) ├── BMS-986446 Low Dose (n=~119) ├── BMS-986446 Medium Dose (n=~119) └── BMS-986446 High Dose (n=~119)