🧠 Donanemab Amyloid Removal Trial Simulator

Recognizing Pyroglutamate-Modified Amyloid Plaque

Donanemab binds a modified amyloid epitope specific to established plaque.

• N3pG-Aβ: Target epitope (placeholder — pyroglutamate form)
• IgG1: Antibody class (placeholder — humanized mAb)
• IV infusion: Route (placeholder — monthly dosing)
• High: Plaque specificity (placeholder — mature plaque only)

Antibody-plaque recognition mechanism

Placeholder: donanemab targets pyroglutamate-modified amyloid on plaque surfaces.

Amyloid Plaque Removal Over the Trial Course

Plaque burden falls month over month as antibody exposure accumulates.

• 4 weeks: Dosing interval (placeholder — IV infusion)
• 18 months: Trial duration (placeholder — TRAILBLAZER-style)
• Progressive: Burden decline (placeholder — dose-dependent)
• MRI checks: ARIA monitoring (placeholder — safety surveillance)

Plaque clearance trajectory

Placeholder: microglia-mediated clearance reduces plaque volume over successive visits.

PET-Based Clearance Confirmation

Amyloid PET scans quantify Centiloid burden to confirm clearance.

• Amyloid PET: Imaging modality (placeholder — florbetapir tracer)
• <24.1 CL: Clearance threshold (placeholder — illustrative cutoff)
• Periodic: Scan cadence (placeholder — every few months)
• Centiloid: Readout unit (placeholder — standardized scale)

Interpreting the PET clearance signal

Placeholder: Centiloid values below threshold indicate amyloid-negative status.

Treatment Discontinuation Once Cleared

Dosing is stopped for participants who reach confirmed clearance.

• Threshold-based: Discontinuation rule (placeholder — stop on clearance)
• If burden returns: Re-treatment (placeholder — monitored)
• Limit exposure: Rationale (placeholder — reduce ARIA risk)
• Novel: Design feature (placeholder — vs. fixed dosing)

Fixed-duration dosing design

Placeholder: clearance-triggered discontinuation distinguishes this trial design.

Trial Cognitive Outcome Measurement

Cognitive and functional scales measure whether clearance slows decline.

• iADRS: Primary endpoint (placeholder — integrated scale)
• CDR-SB: Secondary endpoint (placeholder — functional decline)
• vs. placebo: Comparison (placeholder — slowed decline)
• Early AD: Population (placeholder — biomarker-confirmed)

Linking clearance to clinical benefit

Placeholder: cognitive trend compared between cleared and ongoing-decline groups.

Placeholder highlight: amyloid clearance associates with modestly slowed cognitive decline.