F-18Flornaptitril is a novel PET radiotracer developed by CereMark Pharma for imaging tau pathology in Alzheimer's disease. This Phase 3 clinical trial evaluates its utility in predicting Alzheimer's disease progression and differentiating tauopathies.
| Field |
Value |
| NCT Number |
NCT06254469 |
| Phase |
Phase 3 |
| Status |
Recruiting |
| Sponsor |
CereMark Pharma |
| Condition |
Alzheimer's Disease, Cognitively Normal |
| Participants |
230 |
| Intervention |
F-18Flornaptitril PET scan |
| Primary Outcome |
Tau deposition quantification |
Flornaptitril is a fluorine-18 labeled tau PET tracer that binds to neurofibrillary tau tangles in the brain:
- Target: Hyperphosphorylated tau protein in neurofibrillary tangles (NFTs)
- Binding Profile: Selective for paired helical filament (PHF) tau over amyloid
- Signal: F-18 emission detected via PET imaging
- Advantage: May differentiate AD tau from other tauopathies
The development of tau PET tracers is crucial because:
- Tau Correlates with Cognition: NFT burden correlates better with cognitive decline than amyloid
- Diagnostic Differentiation: Can help differentiate AD from other dementias
- Disease Staging: Tau PET can determine disease stage and progression
- Treatment Response: Useful for monitoring anti-tau therapy efficacy
Primary:
- Assess diagnostic performance of Flornaptitril PET for AD prediction
- Evaluate sensitivity and specificity for detecting tau pathology
Secondary:
- Compare with established tau PET tracers (e.g., flortaucipir)
- Assess correlation with cognitive measures
- Evaluate utility in differentiating AD from other tauopathies
- Age 50-85 years
- Cognitively normal or mild cognitive impairment
- Ability to undergo PET imaging
- No significant neurological conditions (except AD)
- Contraindications to PET imaging
- Active psychiatric conditions
- Significant brain pathology other than AD
Tau PET imaging has evolved significantly since the first generation of tau tracers:
- First Generation (2013+): Flortaucipir (AV-1451) - first FDA-approved tau PET tracer
- Second Generation (2017+): PI-2620, PK-11195 analogs - improved 4R-tau binding
- Third Generation (2020+): Flornaptitril - enhanced selectivity and novel binding sites
Flornaptitril binds to a distinct conformation of tau filaments:
- Primary Site: Microtubule-binding repeat domain (R3-R4)
- Selectivity: 10-fold preference for PHF tau over non-pathological tau
- Off-target: Minimal white matter binding compared to first-gen tracers
- Kinetics: Fast brain uptake, adequate clearance
| Tracer |
Target |
Status |
Advantages |
| Flortaucipir (AV-1451) |
PHF tau |
Approved |
Validated in AD |
| Flornaptitril |
PHF tau |
Phase 3 |
Potential CTE differentiation |
| PI-2620 |
4R tau |
Phase 2 |
PSP/CBD specific |
- Early Detection: Identify tau pathology before clinical symptoms
- Differential Diagnosis: Help distinguish AD from FTD, PSP, CBD
- Prognosis: Predict disease progression
- Clinical Trials: Enrichment biomarker for anti-tau trials
- Chronic Traumatic Encephalopathy: Potential to differentiate CTE from AD
Tau PET imaging represents a significant market opportunity:
- Global Tau PET Market: ~$800M annually
- Growth Drivers: Alzheimer's prevalence, clinical trial demand, precision medicine
- Competitive Landscape: 5+ companies developing next-gen tau tracers
- Reimbursement: Active discussion for Medicare coverage in 2026
The Flornaptitril PET scan follows a standardized protocol:
- Radiotracer Administration: ~185 MBq (5 mCi) IV injection
- Scan Window: 80-100 minutes post-injection
- Duration: 20-minute acquisition
- Repeat: Baseline and 12-month follow-up scans
- Safety Monitoring: Vital signs before and after scan
- Total Time: ~2.5 hours per visit
- Radiation Dose: ~3.5 mSv per scan (comparable to CT)
- Repeat Scans: Two visits over 12 months
- Cognitive Testing: Included in each visit (~45 minutes)
This trial is actively recruiting. For more information, visit ClinicalTrials.gov NCT06254469.
- Tau PET Imaging
- Tau PET Tracers
- Alzheimer's Disease Biomarkers
- Differential Diagnosis of Tauopathies
^1]: F-18Flornaptitril PET in Prediction of Alzheimer's Disease. 2024.