A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL593 in Healthy Participants and Participants With Frontotemporal Dementia (FTD-GRN) [sponsored by Denali Therapeutics, Inc.]

Summary: 

DNL593 is an experimental treatment that was designed to restore normal levels of the progranulin protein (PGRN) in the brain. The study will collect data to evaluate how safe DNL593 is, as well as how well the body handles it (pharmacokinetics), what it does in the body (pharmacodynamics), and whether people can handle taking it without too many side effects (tolerability). The study is set up as a randomized, placebo-controlled study which means that participants will either receive the experimental treatment DNL593 or a placebo (something that looks like the experimental treatment but has no experimental medicine in it). It is also double blind which means that participants will not know if they received DNL593 or a placebo and the study doctor will not know either. Only the researchers analyzing the data will have that information.

Who is eligible?

• Men and women aged 18 to 80 years
• Women who can no longer have children (sterilized or post-menopausal) or who are using select highly effective birth control methods
• Body mass index between 18 and 32 
• Does not currently have a positive pregnancy test and is not currently breastfeeding
• Has not been diagnosed with any major disorder (neurologic, psychiatric, cardiac, etc)
• Does not have a history of stroke or cognitive impairment (other than due to FTD), seizure (within 5 years of screening), head trauma or loss of consciousness (within 2 years of screening)
• Carries a pathogenic progranulin gene (GRN) variant
• Has a symptom related to FTD with a Clinical Dementia Rating® plus National Alzheimer's Coordinating Center frontotemporal lobar degeneration global score ≥ 0.5
• Is not required to have a clinical diagnosis of FTD

Interested individuals meeting the above requirements should contact the study coordinator for additional requirements and exclusions if interested in participating.

What will happen during the study?

This study will randomly assign participants into the experimental group where participants will receive the experimental treatment or the placebo group where participants will receive a placebo, something that looks like the experimental treatment but has no medicine in it. Both the experimental treatment and placebo will be given through an intravenous infusion (needle in the arm). Participants will receive multiple doses over the course of the study.

​​What are they measuring to evaluate the experimental treatment?

• Side effects and reactions to the experimental treatment
• Changes in vital signs like blood pressure, heart rate, body temperature, etc.
• Changes in electrocardiogram (ECG) which measures heart function
• Changes in physical or neurological exam
• Changes in suicide rating scale
• How long the experimental treatment stays in the blood and spinal fluid

How long will participants be involved in the study?

Study participants will be monitored for 25 weeks.

Individuals who complete 25 weeks in either the treatment or placebo groups will be eligible to receive an additional 18 months of treatment in an optional open label extension. In the open label extension, all participants will receive the experimental medicine; there is no placebo group in the open label extension.