A phase 1, randomized, placebo-controlled, double-blind study to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of DNL151 in healthy volunteers.

Denali Therapeutics Inc.
Study Design: 
The study is a double-blind, randomized, placebo-controlled, single ascending dose (SAD), multiple ascending dose (MAD), and 28-day safety study in healthy volunteers.
Outcome Measures: There are seven primary and two secondary outcome measures. The primary ones are: 1. Incidence of treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs) and discontinuations due to TEAEs; 2. Maximum observed concentration (Cmax) in plasma; 3. Time to maximum observed concentration (Tmax) in plasma; 4. The area under the concentration-time curve from time zero extrapolated to infinity (AUC0-∞) in plasma (SAD only); 5. Area under the concentration-time curve from time zero to the time of last quantifiable concentration (AUC [0-last]) in plasma; 6. The area under the concentration-time curve over a dosing interval (AUC0-T) in plasma (MAD only); 7. Apparent terminal elimination half-life (t1/2) in plasma. The timeframe for the measures above is up to 42 days. Secondary outcome measures are the concentration of DNL151 in CSF (following selected single and multiple doses) up to 13 days from initiation; and the pharmacodynamics of DNL151 in whole blood as measured by the percent change from baseline in pS935, up to 42 days.
This study is a large, classic design phase 1 safety study in healthy volunteers. Inclusion and exclusion criteria are straightforward. The trial has been conducted in parallel with a phase 1b in 25 PwP (NCT04056689), producing data to support progression into the next phase.