DNL921 safety and pharmacology in healthy adults and people with 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 is a Phase 1/1b, multicenter, randomized, placebo-controlled, double-blind study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple doses of DNL921 in healthy participants and in individuals with Alzheimer's disease. The primary goal is to gather safety data and characterize how the drug is processed in the body, which will guide dose selection for future research. Results from PK/PD assessments will inform design decisions for subsequent studies. The trial uses a placebo control and rigorous blinding to reduce bias while evaluating potential differences between healthy and AD participants.

Why it matters

Who can join: the full rules

Key Inclusion Criteria (Healthy Participants):

* Are male or female of non-childbearing potential and are aged 18 through 60 years at the time of screening
* Have a BMI of 18 through 32 kg/m2 and a body weight of at least 50 kg
* For female participants: Are of non-childbearing potential
* For male participants: Are surgically sterile by bilateral orchidectomy, or are abstinent, or agree to use two acceptable forms of contraception

Key Exclusion Criteria (Healthy Participants):

* Have any history of clinically significant neurological, psychiatric, endocrine, pulmonary, cardiovascular, gastrointestinal, hepatic, pancreatic, renal, metabolic, hematological, immunological, or allergic disease, or other major disorders
* Have a positive serum pregnancy test or are currently lactating or breastfeeding
* Have been hospitalized during the 4 weeks prior to screening

Key Inclusion Criteria (Participants with AD):

* Are male or female of non-childbearing potential and aged 50 to 75 years at the time of screening
* Have a BMI between 18 and 32 kg/m2 and a body weight of at least 45 kg
* Have a diagnosis of probable mild to moderate AD dementia based on NIA AA 2011 criteria, including amnestic or nonamnestic presentation at screening or prodromal AD (consistent with the NIA-AA diagnostic criteria and guidelines for mild cognitive impairment due to AD)
* Have supportive evidence of AD pathology by the following:

  * Plasma ptau217/Abeta42 positive
  * Positive amyloid PET scan
* For female participants: Are of non-childbearing potential
* For male participants: Are surgically sterile by bilateral orchidectomy, or are abstinent, or agree to use two acceptable forms of contraception

Key Exclusion Criteria (Participants with AD):

* Have other clinically significant neurological or cognitive disorders affecting the CNS, as determined by the investigator, other than AD
* Have specific 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 treated with curative intent (such as prostate cancer) at low risk of recurrence
* Have a positive serum pregnancy test or are currently lactating or breastfeeding
* Have been hospitalized during the 4 weeks prior to screening
* Have had previous anti-amyloid or anti-tau immunotherapy (including active immunization) or have participated in experimental gene therapy or cell therapy at any time

Where it's running

• Clinical Site(s)
  Manchester, 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.