Study of Trontinemab Compared to Placebo for Patients with Early Symptomatic Alzheimer's Disease

Initial screening and confirmation

Your vision and hearing will be assessed to ensure they are adequate for completing the tests required during the study.

Your ability to perform memory and thinking tests will be evaluated. This includes a test called Mini-Mental State Examination, where your score must be 22 or higher.

Your overall cognitive function will be assessed using the Clinical Dementia Rating scale, which should show a score of 0.5 or 1.0.

A memory test called Repeatable Battery for the Assessment of Neuropsychological Status will be performed. Your delayed memory score must be 85 or lower to qualify.

Confirmation of Alzheimer's disease pathology will be required through either a PET scan (a brain imaging test that shows amyloid protein deposits) or a cerebrospinal fluid test (a sample of fluid from around your spine).

A study partner must be available to participate with you throughout the study. This person should know you well and can provide information about your daily activities and symptoms.

Randomization and treatment assignment

You will be randomly assigned to receive either trontinemab (the study medication) or placebo (an inactive substance that looks like the study medication but contains no active ingredient).

Neither you nor the study staff will know which treatment you are receiving. This is called a double-blind study design.

Treatment phase

You will receive your assigned treatment through an intravenous infusion (a slow injection into a vein) or intravenous bolus injection (a quick injection into a vein).

The treatment will continue for 72 weeks (approximately 18 months).

The exact dosage and frequency of administration will be determined by the study protocol.

Regular monitoring visits

Throughout the 72-week treatment period, you will attend regular visits for monitoring and assessments.

At these visits, your thinking abilities and memory will be tested using several assessments, including the Alzheimer's Disease Assessment Scale-Cognition 13, which evaluates various aspects of cognitive function.

Your ability to perform daily activities will be assessed using the Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory.

Your overall cognitive and functional status will be evaluated using the integrated Alzheimer's Disease Rating Scale.

The Mini-Mental State Examination will be repeated to track changes in your mental state.

The Clinical Dementia Rating assessment will be performed to monitor any progression in your condition.

Safety monitoring

Blood samples will be collected regularly to check for any changes in laboratory values and to measure specific proteins in your blood, including phosphorylated tau-217 and glial fibrillar acidic protein.

Your vital signs (such as blood pressure, heart rate, and temperature) will be measured at each visit.

Physical examinations, including neurological assessments, will be performed regularly.

An electrocardiogram (a test that records the electrical activity of your heart) will be performed periodically.

You will be asked questions from the Columbia-Suicide Severity Rating Scale to monitor your mental health and safety.

Any side effects or health problems you experience will be recorded and evaluated throughout the study.

Brain imaging assessments

Regular MRI scans (magnetic resonance imaging) will be performed to monitor for specific changes in your brain, including amyloid-related imaging abnormalities. These abnormalities can include swelling or fluid accumulation (ARIA-E) or small areas of bleeding (ARIA-H).

Amyloid PET scans will be conducted to measure the amount of amyloid protein in your brain. These scans use small amounts of radioactive tracers, including substances called florbetapir, flutemetamol, or florbetaben, which are injected into a vein.

If you are selected for a subset group, tau PET scans will be performed to measure tau protein levels in your brain using a tracer called florquinitau.

Cerebrospinal fluid collection (subset of participants)

If you are selected for a subset group, samples of cerebrospinal fluid will be collected at certain time points.

These samples will be analyzed to measure specific biomarkers, including phosphorylated tau-181, neurogranin, and amyloid-beta 42, which help track disease progression.

Monitoring for infusion reactions

During and after each infusion, you will be monitored for any infusion-related reactions, which are side effects that can occur during or shortly after receiving the medication through a vein.

The type, frequency, severity, and timing of any such reactions will be recorded.

Antibody testing

Blood samples will be collected to check if your body develops anti-drug antibodies (proteins produced by your immune system in response to the study medication).

The presence and levels of these antibodies will be measured throughout the study and compared to baseline levels.

Final assessments at week 72

At the end of the 72-week treatment period, all cognitive, functional, and safety assessments will be repeated.

Final brain imaging scans will be performed to measure changes in amyloid and tau protein levels.

Blood and possibly cerebrospinal fluid samples will be collected for final biomarker measurements.

A comprehensive evaluation of your overall health and any side effects experienced during the study will be conducted.