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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
75 Years
Healthy volunteers
No
Key Inclusion Criteria:
* BMI of ≥18 to \< 32 kg/m2 and body weight of ≥45 kg
* Have a diagnosis of probable AD dementia based on NIA AA 2011 criteria, including amnestic or nonamnestic presentation at screening
* Have supportive evidence of AD pathology via historical records or laboratory testing at screening for amyloid positivity
* Have AD severity defined as the following at screening:
* A Clinical Dementia Rating global score of 0.5 or 1
* A Mini-Mental State Examination score of 20 to 30 (inclusive)
Key Exclusion Criteria:
* Have clinically significant neurological or cognitive disorders affecting the CNS other than AD, as determined by the investigator
* Have clinically significant psychiatric conditions
* Have any history of unstable or poorly controlled endocrine, pulmonary, cardiovascular, gastrointestinal, hepatic, hematological, or other significant medical condition that, in the opinion of the investigator, may interfere with the completion or interpretation of study assessment
* Have had a malignancy within 5 years before screening, except fully resected basal cell carcinoma or other malignancies (such as prostate cancer) at low risk of recurrence, depending on investigator and medical monitor agreement
* Have had previous anti amyloid or anti tau immunotherapy (including active immunization)
* Note: ADAD participants who have participated in previous passive anti-amyloid immunotherapy \> 6 months previously will be allowed, contingent on investigator and Sponsor agreement
* Have had previous exposure to gene therapy
Primary outcome measure(s)
Incidence and severity of treatment-emergent adverse events (TEAEs) throughout the double-blind period — 37 weeks
Trial sites (4)
Facility
City
Region
Status
Clinical Site(s)
's-Hertogenbosch
Netherlands
Recruiting
Clinical Site(s)
Amsterdam
Netherlands
Recruiting
Clinical Site(s)
Zwolle
Netherlands
Recruiting
Clinical Site(s)
London
United Kingdom
Recruiting
Official registry record
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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