This is a Phase 1b, multicenter, randomized, placebo-controlled, double-blind, multiple ascending dose (MAD) study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of DNL628 in participants with early Alzheimer's disease (AD), defined as mild cognitive impairment, or mild AD with biomarker evidence of amyloid positivity. Note: In the Netherlands, this study includes an open-label extension.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
68
Multiple ascending doses
Multiple ascending doses
Clinical Site(s)
's-Hertogenbosch, Netherlands
RECRUITINGClinical Site(s)
Amsterdam, Netherlands
RECRUITINGClinical Site(s)
Zwolle, Netherlands
RECRUITINGClinical Site(s)
London, United Kingdom
RECRUITINGIncidence and severity of treatment-emergent adverse events (TEAEs) throughout the double-blind period
Time frame: 37 weeks
PK parameter: Maximum concentration (Cmax) of DNL628 in plasma
Time frame: 37 weeks
PK Parameter: Time to reach maximum concentration (tmax) of DNL628 in plasma
Time frame: 37 weeks
PK Parameter: Minimum concentration (Cmin) of DNL628 in plasma
Time frame: 37 weeks
PK Parameter: Area under the concentration-time curve (AUC) from time zero to time of last measurable concentration (AUClast) of DNL628 in plasma
Time frame: 37 weeks
PK Parameter: AUC from time 0 to the end of the dosing interval (AUCτ) of DNL628 in plasma
Time frame: 37 weeks
PK Parameter: terminal elimination half-life (t1/2) of DNL628 in plasma
Time frame: 37 weeks
PK Parameter: Accumulation ratio of DNL628 in plasma
Time frame: 37 weeks
Change from baseline in total tau and ptau181 as measured in CSF
Time frame: 25 weeks
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