What is the aim of the study?

This study is testing a new investigational medicine called LY3954068 for people with Alzheimer’s disease.

LY3954068 is an investigational treatment that is intended to help the body make less of a protein called tau. Tau helps support brain cells, but in Alzheimer’s disease, too much tau can clump together and cause damage which may lead to memory and thinking problems. This medicine is designed to lower the amount of tau so that these harmful clumps form more slowly, which may help slow the disease.

The study aims to understand:
- If LY3954068 is safe for people with Alzheimer’s disease and to see how well people can tolerate it.
- How LY3954068 works inside the body, including what it does and how the body handles it after it is given.

The LY3954068 or placebo is given as an injection into the space around the spine so it can reach the brain more directly.

This study is a double-blind placebo-controlled trial and people in the study will be put into their treatment groups at random. This means:
- Some people will get LY3954068
- Some people will get a placebo (a dummy treatment that has no medicine in it).
- Neither the participant, nor their study doctor will know who is getting which treatment during the first part of the study. This helps make the results fair.

Find more information about why studies use blinding, randomisation and placebo controls.

The study is made up of two parts, A and B.
- Each participant in Part A will receive 1 dose of LY3954068 or placebo (no active drug) given into the spinal fluid.
- Each participant in Part B will receive multiple doses of either LY3954068 or placebo administered into the spinal fluid.
- Participants will also potentially have an opportunity to join a separate study where participants would receive LY3954068.

LY3954068 is an experimental medicine. This means health authorities (like the U.S. Food and Drug Administration and European Medicines Agency) have not approved LY3954068 for the treatment of Alzheimer’s disease.

The study also uses a drug called Flortaucipir F18 to monitor changes in the brain linked to Alzheimer’s disease. Flortaucipir F18 is a special type of medicine that gives off a very small amount of radiation. Medicines like this are called radiopharmaceuticals. Doctors use them before scans to help take clear pictures inside the body. Everyone in the study will have Flortaucipir F18 before their positron emission tomography (PET) scans. 

What will participants be asked to do during the study?

During the study, participants will:
- Have some laboratory tests, such as blood, urine or spinal fluid tests. These tests help doctors check for any new side effects, such as symptoms or health changes that might happen after receiving the study medicines or placebo.

- Have brain scans called PET scans and magnetic resonance imaging (MRI) scans. These scans take detailed pictures of the brain to help doctors check brain health and safety.

- Complete tests that look at memory, thinking, and emotional wellbeing.

The study will last up to approximately 45 weeks for Part A, and, 100 weeks for Part B, including the screening period.

If participants would like more details about the tests, procedures, or number of visits, the study team can provide full information.