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Recruiting NCT07328451

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

Phase I Interventional Alzheimer Disease, Early Onset

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: DNL628, Placebo.
Who it may be relevant to
Registry conditions: Alzheimer Disease, Early Onset. Basic parameters: 18 years — 75 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
Netherlands, United Kingdom
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official 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

Overview

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. Note: In the Netherlands, this study includes an open-label extension.

Interventions

  • Drug DNL628
    Multiple ascending doses
  • Drug Placebo
    Multiple ascending doses

Primary outcome measures

  • Incidence and severity of treatment-emergent adverse events (TEAEs) throughout the double-blind period [Time frame: 37 weeks]
Secondary outcome measures (8)
  • PK parameter: Maximum concentration (Cmax) of DNL628 in plasma [Time frame: 37 weeks]
  • PK Parameter: Time to reach maximum concentration (tmax) of DNL628 in plasma [Time frame: 37 weeks]
  • PK Parameter: Minimum concentration (Cmin) of DNL628 in plasma [Time frame: 37 weeks]
  • PK Parameter: Area under the concentration-time curve (AUC) from time zero to time of last measurable concentration (AUClast) of DNL628 in plasma [Time frame: 37 weeks]
  • PK Parameter: AUC from time 0 to the end of the dosing interval (AUCτ) of DNL628 in plasma [Time frame: 37 weeks]
  • PK Parameter: terminal elimination half-life (t1/2) of DNL628 in plasma [Time frame: 37 weeks]
  • PK Parameter: Accumulation ratio of DNL628 in plasma [Time frame: 37 weeks]
  • Change from baseline in total tau and ptau181 as measured in CSF [Time frame: 25 weeks]

Eligibility criteria

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)

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Randomized
Model
Sequential
Masking
Double blind
Primary purpose
Treatment

Study locations

Netherlands · 3 centers
  • Clinical Site(s) — 's-Hertogenbosch
  • Clinical Site(s) — Amsterdam
  • Clinical Site(s) — Zwolle
United Kingdom · 1 center
  • Clinical Site(s) — London

Identifiers

NCT: NCT07328451 · DNLI-K-0001 · 2025-523515-11-00

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗