Alzheimer Disease, Early OnsetPhase 1NCT07328451
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL628 in Participants With Early Alzheimer's Disease
A Phase 1 study testing DNL628 in people with Alzheimer Disease, Early Onset, run by Denali Therapeutics Inc. at 4 sites in 2 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Alzheimer Disease, Early Onset
- What is being tested?
- DNL628
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 68 participants
- Where
- 4 sitesin 2 countries
- Study dates
- 30 Jan 2026to Feb 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
4 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
4 sites in 2 countries
Netherlands3 sites, 3 recruiting
- Recruiting
Clinical Site(s)
's-Hertogenbosch
- Recruiting
Clinical Site(s)
Amsterdam
- Recruiting
Clinical Site(s)
Zwolle
About this study
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
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.
- Conditions
- Alzheimer Disease, Early Onset
- Being tested
- DNL628, Placebo
- Keywords
- Alzheimer's Disease
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DNL628Drug
Multiple ascending doses
PlaceboDrug
Multiple ascending doses
| Study group | Role | What they receive |
|---|---|---|
| Experimental Arm | Experimental | Not described Receives: Drug: DNL628 |
| Placebo Arm | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and severity of treatment-emergent adverse events (TEAEs) throughout the double-blind period
Measured: 37 weeks
Secondary outcomes (8)
PK parameter: Maximum concentration (Cmax) of DNL628 in plasma
Measured: 37 weeks
PK Parameter: Time to reach maximum concentration (tmax) of DNL628 in plasma
Measured: 37 weeks
PK Parameter: Minimum concentration (Cmin) of DNL628 in plasma
Measured: 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
Measured: 37 weeks
PK Parameter: AUC from time 0 to the end of the dosing interval (AUCτ) of DNL628 in plasma
Measured: 37 weeks
PK Parameter: terminal elimination half-life (t1/2) of DNL628 in plasma
Measured: 37 weeks
PK Parameter: Accumulation ratio of DNL628 in plasma
Measured: 37 weeks
Change from baseline in total tau and ptau181 as measured in CSF
Measured: 25 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2026
- Study start30 Jan 2026
- Primary completionFeb 2027 (estimated)
- Study completionFeb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer Disease, Early OnsetStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 68 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Denali Therapeutics Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, Study director, Denali Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07328451
- Sponsor's protocol ID
- DNLI-K-0001
- Other IDs
- 2025-523515-11-00, 2025
- Status last verified
- Jun 2026
- First submitted
- 24 Dec 2025
- Last updated
- 1 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT07328451
- Acronym / sponsor ID
- DNLI-K-0001
- Conditions
- Alzheimer Disease, Early Onset
- Keywords
- Alzheimer's Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 68 participants (estimated)
- Lead sponsor
- Denali Therapeutics Inc.Industry (pharma, biotech, devices)
- Study start
- 30 Jan 2026 (actual)
- Primary completion
- Feb 2027 (estimated)
- Study completion
- Feb 2027 (estimated)
- First posted
- 9 Jan 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental Arm | Experimental | Drug: DNL628 |
| Placebo Arm | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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:
Key exclusion criteria (7 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DNL628Multiple ascending doses | Drug | Experimental Arm |
| PlaceboMultiple ascending doses | Drug | Placebo Arm |
Primary outcome
Incidence and severity of treatment-emergent adverse events (TEAEs) throughout the double-blind period
Time frame: 37 weeks
8 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Medical Monitor study director
Denali Therapeutics
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing DNL628 in people with Alzheimer Disease, Early Onset, run by Denali Therapeutics Inc. at 4 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 1 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Netherlands, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Clinical Trials at Denali Therapeutics (Email:, clinical-trials@dnli.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence and severity of treatment-emergent adverse events (TEAEs) throughout the double-blind period (time frame: 37 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jul 2026; AzTrials last refreshed its copy on 6 Nov 2026.