A study testing trontinemab compared to placebo in patients with early Alzheimer's disease including mild cognitive impairment and mild dementia

Initial assessment and baseline measurements

At the start of the study, your cognitive function will be assessed using several standardized tests. These include the Mini-Mental State Examination, which evaluates memory and thinking skills, the Clinical Dementia Rating, which assesses the severity of cognitive symptoms, and the Repeatable Battery for the Assessment of Neuropsychological Status, which measures memory abilities.

A brain scan called an amyloid PET scan will be performed to measure the level of amyloid protein in your brain. Amyloid is a protein that accumulates in the brains of people with Alzheimer's disease.

Blood samples will be collected to measure specific biomarkers, including p-tau217 and glial fibrillar acidic protein. These are substances in the blood that can indicate disease activity.

Physical examinations, including neurological assessments, will be conducted. Your vital signs such as blood pressure and heart rate will be measured, and an electrocardiogram will be performed to check your heart's electrical activity.

Laboratory tests will be performed on your blood samples to assess your general health.

A mental health assessment using the Columbia-Suicide Severity Rating Scale will be completed to evaluate your emotional well-being.

These baseline measurements will serve as reference points to compare changes throughout the study.

Treatment assignment and medication administration

You will be randomly assigned to receive either trontinemab or placebo. A placebo is an inactive substance that looks identical to the actual medication but contains no active treatment. Neither you nor the study staff will know which treatment you are receiving.

The assigned medication will be administered through an intravenous infusion, which means it will be given directly into a vein through a needle, typically in your arm.

The infusion will be given at regular intervals throughout the study period. The exact frequency and dosage will be determined by the study protocol.

Regular monitoring visits through Week 72

Throughout the 72-week treatment period, you will attend scheduled visits at the study site.

During these visits, your cognitive function will be regularly assessed using various tests including the Alzheimer's Disease Assessment Scale-Cognition 13, which evaluates memory, language, and thinking abilities.

Your ability to perform daily activities will be evaluated using the Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory. This assessment measures both basic daily tasks and more complex activities such as managing finances or using household appliances.

The Clinical Dementia Rating, Sum of Boxes will be used to track changes in your cognitive and functional abilities across multiple areas.

The Integrated Alzheimer's Disease Rating Scale will be used to provide a comprehensive assessment of your condition.

Physical examinations, vital signs measurements, and electrocardiograms will be performed regularly to monitor your overall health.

Blood samples will be collected at scheduled intervals to monitor blood biomarkers and to check for the presence of anti-drug antibodies, which are proteins your immune system might produce in response to the medication.

Laboratory tests will be conducted regularly to monitor your general health and detect any potential side effects.

Mental health assessments using the Columbia-Suicide Severity Rating Scale will be repeated periodically.

Brain imaging assessments

During the study, magnetic resonance imaging scans of your brain will be performed at specific intervals. These scans will monitor for ARIA-E and ARIA-H, which are imaging findings that can occur with amyloid-lowering treatments. ARIA-E refers to fluid accumulation in the brain, while ARIA-H refers to small areas of bleeding in the brain.

Additional amyloid PET scans will be performed at scheduled time points to measure changes in the amount of amyloid protein in your brain.

If you are selected for a subset group, tau PET scans may be performed to measure the level of tau protein in your brain. Tau is another protein that accumulates abnormally in Alzheimer's disease.

For the PET scans, you will receive an injection of a radioactive tracer substance. Different tracers may be used depending on the type of scan: florbetapir, flutemetamol, florbetaben, or florquinitau. These substances are given as an intravenous injection and allow the scanner to visualize specific proteins in your brain.

Cerebrospinal fluid collection

If you are selected for a subset group, samples of cerebrospinal fluid may be collected at baseline and at Week 72. Cerebrospinal fluid is the liquid that surrounds your brain and spinal cord.

The fluid will be analyzed to measure biomarkers including phosphorylated tau 181, neurogranin, and amyloid-beta 42. These substances provide information about disease processes occurring in the brain.

Safety monitoring throughout the study

Throughout the entire study period, any side effects or health problems you experience will be recorded and assessed. This includes both minor symptoms and more serious health events.

Special attention will be given to monitoring for infusion-related reactions, which are symptoms that can occur during or shortly after receiving the intravenous medication. These may include symptoms such as fever, chills, or discomfort.

The brain imaging scans will be carefully reviewed to detect and monitor any ARIA-E or ARIA-H findings.

Your overall health status will be continuously monitored through regular assessments and laboratory tests.

Final assessment at Week 72

At Week 72, comprehensive final assessments will be performed, similar to those conducted at baseline.

All cognitive tests will be repeated to measure changes from the beginning of the study, including the Clinical Dementia Rating, Sum of Boxes, Alzheimer's Disease Assessment Scale-Cognition 13, activities of daily living assessments, and other cognitive measures.

Final blood samples will be collected to measure biomarkers.

A final amyloid PET scan will be performed to assess changes in brain amyloid levels.

If you are in the subset group, a final tau PET scan and cerebrospinal fluid collection may be performed.

Final physical examinations, vital signs measurements, electrocardiogram, and laboratory tests will be completed.

A final mental health assessment will be conducted.

These final measurements will be compared to your baseline results to determine the effects of the treatment over the 72-week period.