A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL593 in Healthy Participants and Participants With Frontotemporal Dementia (FTD-GRN)

To join this study, specific requirements must be met. For the first part, healthy men and women (who are past menopause or have had a hysterectomy/sterilisation) between 18 and 55 years old are needed. They also need to have a body mass index (BMI) within a certain range.

For the second part of the study, which involves people with frontotemporal dementia (FTD-GRN), participants must be men or women (who are past menopause, sterilised, or using highly effective contraception) between 18 and 80 years old, with a similar BMI requirement. Importantly, they must have a confirmed GRN genetic mutation, which is linked to this specific form of FTD.

However, some conditions would prevent someone from joining. This includes a history of many serious health issues such as significant heart, lung, kidney, liver, or neurological problems (like a recent stroke or seizures). Also, anyone with a history of most cancers, pregnant or breastfeeding women, or those with significant allergies would not be able to participate. The research team will carefully check everyone's medical history to ensure their safety in the study.

If you take part in this study, what you do will depend on which part you are in. Healthy volunteers in Part A will receive a single dose of the study medicine (DNL593) or a placebo, requiring several visits for health checks and blood tests. Participants in Part B, who have FTD-GRN, will receive multiple doses of DNL593 or a placebo over approximately 25 weeks (about 6 months). This will involve regular visits to the clinic for assessments, including health checks, memory and thinking tests, and blood samples, to monitor the medicine's effects and your general health. There will also be follow-up calls or visits after the main treatment period.

For those who complete Part B and meet certain criteria, there's an optional Part C, where you could continue receiving DNL593 for an additional 18 months. This optional extension would also involve regular clinic visits and health monitoring. The total duration of participation varies depending on the part you are in, and whether you choose to enter the optional extension.