Phase 1/2 Clinical Trial of LY3884963 in Patients With Frontotemporal Dementia With Progranulin Mutations (FTD-GRN)

To join this study, you need to be a man or a woman between 30 and 85 years old. You should have been diagnosed with Frontotemporal Dementia (FTD) that's causing noticeable changes in your behavior, thinking, movement, or language, as assessed by a doctor. Importantly, your FTD must be caused by a specific change in your progranulin (GRN) gene, which will be confirmed by genetic testing.

There are also some general health requirements, such as weighing between 40 kg and 110 kg, and having a body mass index (BMI) between 18 and 34. Any other medicines you're taking should have been stable for at least 8 weeks before starting the study. You'll also need to have up-to-date cancer screenings and a negative test for tuberculosis.

For women, if you're able to have children, you must use highly effective contraception throughout the study. If you're no longer able to have children (e.g., after menopause or certain surgeries), you'll need to meet specific criteria. All participants, or their legal representative, must be able to understand the study and agree to take part by signing a consent form.

If you join this study, you will receive the new medicine, LY3884963, directly into the fluid around your brain and spinal cord (a procedure called intra-cisternal administration). The medicine will be given in increasing doses, starting with a low dose and potentially moving to a medium dose, depending on which group you are in. You might also receive other medicines like methylprednisolone, sirolimus, or prednisone, if needed, as decided by the study doctors.

For the first year, you will have regular visits for check-ups. During these visits, the study team will monitor your safety, using blood tests, scans, and other assessments. They will also look at how your body handles the medicine, called tolerability, and measure levels of important proteins (biomarkers) to see if the medicine is having an effect. They will also assess your FTD symptoms to see if there are any changes.

After the first year, you will continue to be part of the study for another four years. During this longer follow-up period, there will be fewer visits, but the team will still monitor your safety and keep track of certain biomarkers and how your FTD symptoms are progressing. The total length of your participation in this study will be five years.