DNL628 safety, tolerability, and drug behavior in people with early Alzheimer's disease.

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This Phase 1b, multicenter, randomized, placebo-controlled, double-blind multiple ascending dose study will enroll adults with early Alzheimer's disease (mild cognitive impairment or mild AD) who have biomarker evidence of amyloid positivity. Participants will receive ascending doses of DNL628 or matching placebo across multiple cohorts to collect safety, tolerability, pharmacokinetic, and pharmacodynamic data. Key eligibility includes a CDR global score of 0.5–1, MMSE 20–30, and confirmed amyloid positivity, with exclusions for significant psychiatric, neurological, or unstable medical conditions. The primary goals are to define a safe dose range and characterize how the drug is absorbed, distributed, metabolized, and excreted, while secondary analyses will look for PD signals.

Why it matters

Who can join: the full rules

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

Where it's running

• 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

Study contacts

• Study coordinator: Clinical Trials at Denali Therapeutics
• Email: clinical-trials@dnli.com
• Phone: Email:

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.