DNLI-K-0001

• Research type

  Research Study

• Full title

  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

• IRAS ID

  1012999

• Contact name

  Clinical Trials Group .

• Contact email

  clinical-trials@dnli.com

• Sponsor organisation

  Denali Therapeutics Inc.

• Eudract number

  2025-523515-11

• Research summary

  Alzheimer’s Disease (AD) is defined by accumulation of abnormal proteins in the brain. One of these proteins is called tau. Having too much tau may play a role in memory loss and other problems in people with AD. Denali Therapeutics Inc. is developing a novel therapy for AD named DNL628. DNL628 is given via an injection into a vein. After it enters the blood, its specific delivery system helps it enter the brain. DNL628 carries a special piece of genetic material, called antisense oligonucleotide or ASO. In the brain, ASO removes the instruction or message (called mRNA) that a body uses to create tau protein and that is produced by the gene that codes for tau. The ASO does not interact with your DNA. By removing the instruction to create tau protein, it may help lower tau levels. DNL628 is an investigational drug and it is still unknown whether it works against AD.
  In this study, multiple administrations of DNL628 will be tested against placebo over several cohorts. Each cohort will receive a single dose level only. Study assessments will include blood draws, lumbar punctures, ECGs, MRIs, PET scans, memory tests and physical examinations. The main aim is to evaluate if DNL628 in increasing doses causes side effects. Furthermore, the study will investigate how quickly DNL628 enters the blood and how fast the body removes it. Lastly, the study will investigate if DNL628 influences the levels of tau in the brain and other proteins that are related to AD. After completion of each cohort, an open label extension may be offered by the Sponsor, but will require a further protocol amendment and separate consent.

• REC name

  London - West London & GTAC Research Ethics Committee

• REC reference

  25/LO/0685

• Date of REC Opinion

  9 Dec 2025

• REC opinion

  Further Information Favourable Opinion