RecruitingPhase 1NCT07328451

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL628 in Participants With Early Alzheimer's Disease

A Phase 1b, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL628 in Participants With Early Alzheimer's Disease

Sponsor

Denali Therapeutics Inc.

Enrollment

68 participants

Start Date

Jan 30, 2026

Study Type

INTERVENTIONAL

Conditions

Alzheimer Disease, Early Onset

Summary

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.

Eligibility

Min Age: 18 YearsMax Age: 75 Years

Inclusion Criteria6

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)

Exclusion Criteria7

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