Status: Recruiting
Phase: Phase 3
Sponsor: CereMark Pharma
Estimated Enrollment: 230 participants
Study Start: 2025
Estimated Completion: 2028
This Phase 3 clinical trial evaluates F-18Flornaptitril, a novel tau positron emission tomography (PET) tracer, for its ability to predict Alzheimer's disease (AD) progression and differentiate chronic traumatic encephalopathy (CTE) from AD.
¶ Background and Rationale
Current tau PET tracers have significant limitations:
- Limited specificity: Many tracers cannot distinguish between different tauopathies
- Off-target binding: Binding to non-tau structures can confound results
- CTE detection gap: No validated tau PET tracer exists for CTE diagnosis
F-18Flornaptitril is a second-generation tau PET radioligand developed by CereMark Pharma with the following potential advantages:
- High tau selectivity: Specific binding to hyperphosphorylated tau aggregates
- Reduced off-target binding: Minimized binding to melanin and monoamine oxidase
- CTE differentiation: Designed to detect tau pathology patterns unique to CTE
- Early detection capability: Ability to detect tau pathology in pre-symptomatic stages
| Parameter |
Value |
| Design |
Multi-center, cross-sectional imaging study |
| Allocation |
N/A (imaging study) |
| Intervention |
F-18Flornaptitril PET scan |
| Primary Outcome |
Diagnostic accuracy for AD vs. non-AD |
| Secondary Outcomes |
CTE vs. AD differentiation, sensitivity, specificity |
- Participants with suspected Alzheimer's disease
- Participants with suspected CTE
- Cognitively normal controls
- Age range: 50-85 years
- Radiotracer administration: Intravenous injection of F-18Flornaptitril (185-370 MBq)
- Dynamic imaging: 0-90 minutes post-injection
- Standardized uptake value ratio (SUVR): Regional tau deposition quantification
- MRI co-registration: High-resolution T1-weighted MRI for anatomical localization
Alzheimer's disease is characterized by accumulation of hyperphosphorylated tau protein in neurofibrillary tangles (NFTs). Tau PET imaging enables:
- In vivo visualization of tau burden
- Disease staging and progression monitoring
- Correlation with cognitive decline
- Assessment of treatment response
¶ CTE and Tau Pathology
Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive traumatic brain injury. CTE tau pathology has distinct patterns from AD:
- Location: Predominant involvement of cortical sulcal depths
- Pattern: Perivascular distribution of NFTs
- Tau isoform: Primarily 3R/4R tau aggregates
Differentiating CTE from AD is clinically important but challenging. F-18Flornaptitril aims to provide a non-invasive diagnostic tool.
- Age 50-85 years
- Clinical diagnosis of AD, suspected CTE, or cognitively normal
- Capable of undergoing PET/MRI imaging
- Able to provide informed consent
- Willing to participate in follow-up assessments
- Contraindications to PET/MRI imaging
- Active neurological conditions other than AD/CTE
- Severe medical conditions
- Pregnancy or breastfeeding
- Recent participation in other radiotracer studies
- Diagnostic accuracy: Sensitivity and specificity of F-18Flornaptitril for AD detection
- SUVR quantification: Regional tau burden measurement
- CTE-AD differentiation: Ability to distinguish CTE tau patterns from AD
- Cognitive correlation: Association between PET signal and cognitive performance
- Biomarker correlation: Correlation with CSF and blood tau biomarkers
- Longitudinal assessment: Change in tau signal over time
- Adverse events monitoring
- Radiation dosimetry assessment
- Vital signs and laboratory values
- Earlier AD diagnosis before significant cognitive decline
- Differentiation of CTE from AD and other dementias
- Objective biomarker for disease staging
- Understanding tau propagation in vivo
- Supporting clinical trial enrollment for anti-tau therapies
- Biomarker development for disease-modifying treatments