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

Denali Therapeutics

Status and phase

Not yet enrolling

Phase 1

Conditions

Alzheimer Disease, Early Onset

Treatments

Drug: DNL628

Drug: Placebo

Study type

Interventional

Funder types

Industry

Identifiers

NCT07328451

DNLI-K-0001

2025-523515-11-00 (EU Trial (CTIS) Number)

Details and patient eligibility

About

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.

Enrollment

68 estimated patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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