AD - Alzheimer's Disease, MCI
Conditions
Keywords
tau-PET, [18F]Flortaucipir, Phase I, ELI-101, ELI-101-001, AD, Alzheimer's disease, MCI
Brief summary
This is a non randomized, open-label Phase I study in Chinese participants. The goal of this clinical trial is to evaluate the safety and tolerability of a radioactive imaging agent called \[18F\]Flortaucipir Injection, which is used during a PET scan. The study will also measure how the agent moves through the body (pharmacokinetics), where it goes (biodistribution), the amount of radiation exposure (radiation dosimetry), and how well it may help detect signs of disease (preliminary diagnostic efficacy).
Interventions
DRUG[18F]Flortaucipir Injection
A radioactive diagnostic agent intended for brain positron emission tomography (PET) imaging in adult patients with cognitive impairment who are being evaluated for Alzheimer's disease (AD), to estimate the density and distribution of aggregated tau neurofibrillary tangles (NFTs).
Sponsors
Eli Radiopharma
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
* Signed informed consent form (ICF). * Male or female aged 50-85 years. * Education level sufficient to cooperate with neuropsychological testing and obtain reliable results. * Meet the following criteria related to cognitive impairment: 1. CN: No history of cognitive impairment, Aβ-PET negative, MRI without clinically significant neurodegenerative changes. 2. MCI: Meet core criteria for AD-related MCI, Aβ-PET positive, MRI showing neurodegenerative changes. 3. AD: Meet core criteria for probable AD dementia, Aβ-PET positive, MRI showing neurodegenerative changes. * Fertile individuals: No plan for reproduction, sperm/egg donation within 6 months after signing ICF and until 6 months after study drug administration; and agreement to use highly effective contraception (including partner).
Exclusion criteria
* Pregnant (positive pregnancy test at screening or before administration) or breastfeeding women. * Major surgery within 1 month prior to screening, or planned surgery during the study period. * Known allergy to radioactive radiation, alcohol, \[18F\]Flortaucipir injection, or its excipients, or other severe allergic reactions. * Cognitive impairment due to causes other than AD. * Clinically significant infarction or probable multi-infarct dementia. * Current clinically significant psychiatric illness (e.g., major depression, schizophrenia). * History of epilepsy or seizures (except febrile seizures in childhood). * Inability to tolerate PET/MRI or presence of contraindications to PET/MRI. * Other neurodegenerative diseases or dementias other than AD dementia. * Any other condition that, in the investigator's opinion, makes the subject unsuitable for the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence and Severity of Treatment-Emergent Adverse Events (TEAEs) | 6 days post-injection |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) - Total Radioactivity and Parent Compound | Up to 360 mins | Cmax is defined as the highest observed plasma concentration of total radioactivity (measured by gamma counting) and of the unmetabolized parent \[18F\]Flortaucipir |
| Time to Reach Cmax (Tmax) - Total Radioactivity and Parent Compound | Up to 360 mins | Tmax is the time (in minutes) at which the maximum plasma concentration (Cmax) occurs, recorded as the midpoint of the sampling interval during which the maximum is observed. |
| Terminal Half-Life (t½) of Unmetabolized Parent Compound | Up to 360 mins | — |
| Area Under the Plasma Concentration-Time Curve (AUC0-t and AUC0-∞) of Unmetabolized Parent Compound | Up to 360 mins | AUC0-t is calculated using the linear trapezoidal rule from time 0 to the last measurable concentration. AUC0-∞ is extrapolated as AUC0-t + Ct/λz, where Ct is the last quantifiable concentration and λz is the terminal elimination rate constant. |
| Percentage of Unmetabolized Parent Compound in Plasma | Up to 360 mins | — |
| Urinary Radioactive Excretion Rate | 0-60, 60-120, 120-240, 240-360 mins post-injection | Rate of radioactivity excreted in urine, expressed as percentage of injected dose per hour (%ID/h). Measured by gamma counting of collected urine aliquots over specified intervals. |
| Cumulative Urinary Excretion of Radioactivity | Up to 360 mins post-injection | Total cumulative percentage of the injected radioactive dose recovered in urine over time. Calculated as the sum of radioactivity excreted at each collection interval. |
| Percentage of Unmetabolized Parent Compound and Metabolites in Urine | Up to 360 mins post-injection | Relative proportion of total urinary radioactivity that corresponds to the intact \[18F\]Flortaucipir and its known radioactive metabolites. |
| Organ/Tissue Radioactivity Uptake - Percent Injected Dose (%ID) | Up to 240 mins post-injection | Percentage of the injected radioactive dose (%ID) present in each target organ or tissue (e.g., brain, liver, kidneys, lungs, bone marrow, etc.) at specified imaging time points. |
| Mean Standardized Uptake Value (SUVmean) in Target Organs/Tissues | Up to 240 mins post-injection | SUVmean is defined as the mean tissue radioactivity concentration (decay-corrected) normalized by injected dose per body weight. |
| Residence Time (Source Organ Time-Integrated Activity) | Up to 240 mins post-injection | Residence time (also known as time-integrated activity coefficient) for each source organ, expressed as hours (or minutes). |
| Absorbed Dose to Target Organs/Tissues | Up to 240 mins post-injection | Absorbed dose (mGy) to each target organ/tissue (e.g., brain, liver, kidneys, urinary bladder wall, lungs, red marrow, heart wall, spleen, thyroid, etc.) per unit administered activity (mGy/MBq). |
| Effective Dose (Whole-Body) | Up to 240 mins post-injection | — |
| Visual Read Positivity Rate - Overall and by Subject Subgroup | At 80 mins post-injection | Proportion of subjects with a positive PET scan based on visual assessment (blinded, independent readers) using a predefined read criterion |
| Standardized Uptake Value Ratio (SUVR) - Composite Region | At 80 mins post-injection | SUVR is calculated as the mean standardized uptake value (SUV) in a composite target region of interest |
Countries
China
Outcome results
None listed