Alzheimer Disease
Conditions
Brief summary
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple oral doses of DNL747 in subjects with Alzheimer's disease when administered for 29 days in a cross-over design
Detailed description
This is a Phase 1b randomized, placebo-controlled, double-blind, crossover study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of DNL747 in subjects with Alzheimer's disease (AD)
Interventions
DRUGDNL747
DNL747
DRUGPlacebo
Placebo
Sponsors
Denali Therapeutics Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
55 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Women of non-childbearing potential and men, aged 55-85 years * AD diagnosis based on the 2011 National Institute on Aging-Alzheimer's Association Guidelines * Supportive evidence for diagnosis of AD based upon positive CSF Aβ42 test, or documented history of positive amyloid-specific PET scan * Screening MMSE score of 16-26 points * Screening CDR Global Score of 0.5-1.0 * Availability of a person (caregiver) who, in the investigator's judgment, has frequent and sufficient contact with the participant and is able to provide accurate information regarding the participant's cognitive and functional abilities, agrees to provide information at clinic visits that require input for scale completion, assists the participant with compliance for at-home study treatment administration, and signs the necessary consent form (note: the caregiver is not required to stay in the unit) * Approved AD treatments (acetylcholinesterase inhibitors ± memantine) and other prescription medications must be stable for ≥1 month prior to screening and anticipated to be stable over the duration of the study Key
Exclusion criteria
* Clinical history within 2 years of the screening visit or current evidence of any neurological or neurodegenerative disorder other than AD that is associated with transient or sustained alterations in cognition * Magnetic resonance imaging (MRI) at screening (or within 1 year of screening visit) consistent with any neurological or neurodegenerative disorder other than AD that is associated with transient or sustained alterations in cognition
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Subjects with Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Randomization - Day 86 |
| Number of Subjects with clinically significant neurological examination abnormalities | Randomization - Day 86 |
| Number of Subjects with laboratory test abnormalities | Randomization - Day 86 |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetic terminal disposition rate constant (λz) with the respective t1/2 of DNL747 | Randomization - Day 86 |
| Pharmacokinetic measure of maximum observed plasma concentration (Cmax) of DNL747 | Randomization - Day 86 |
| Pharmacodynamic measure of pS166 in PBMCs | Randomization - Day 86 |
| Pharmacokinetic measure of CSF concentrations of DNL747 | Randomization - Day 86 |
| Pharmacokinetic measure of time to reach maximum observed plasma concentration (Tmax) of DNL747 | Randomization - Day 86 |
| Pharmacokinetic measure of area under the plasma drug concentration-time curve (AUC) of DNL747 | Randomization - Day 86 |
Countries
Netherlands, United States
Outcome results
None listed