RecruitingPhase 1

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

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

Lead sponsor

Denali Therapeutics Inc.

Asset

DNL628

Listed sites

Recruiting sites

Enrollment

estimated

Study population

Alzheimer’s disease

Key I/E criteria

•Alzheimer's disease•Amyloid biomarker required•CDR global 0.5•MMSE 20-30

Primary endpoint

•Incidence and severity of treatment-emergent adverse events (TEAEs) throughout

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Ctis2025-523515-11-00

Org study IDDNLI-K-0001

NCT IDNCT07328451

Timeline

Milestones

Study first posted2026-01-09actual

Study start2026-01-30actual

Last update posted2026-07-01actual

Primary completion2027-02estimated (month precision)

Study completion2027-02estimated (month precision)

Assets

Drug assets

DNL628

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age18 Years

Maximum age75 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

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)

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

Endpoints (9)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Safety / tolerability / PK

Other (unclassified)

Tau biomarkers

1 endpoint

Secondary/protocol endpoint

Change from baseline in total tau and ptau181 as measured in CSF

Time frame:25 weeks

Phosphorylated tau 181 (p-tau181)

change from baseline, improvement

Safety / tolerability / PK

6 endpoints

Primary/protocol endpoint

Incidence and severity of treatment-emergent adverse events (TEAEs) throughout the double-blind period

Time frame:37 weeks

event count, event

Secondary/protocol endpoint

PK parameter: Maximum concentration (Cmax) of DNL628 in plasma

Time frame:37 weeks

concentration, descriptive

Secondary/protocol endpoint

PK Parameter: Time to reach maximum concentration (tmax) of DNL628 in plasma

Time frame:37 weeks

time to event, event

Secondary/protocol endpoint

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

concentration, descriptive

Secondary/protocol endpoint

PK Parameter: AUC from time 0 to the end of the dosing interval (AUCτ) of DNL628 in plasma

Time frame:37 weeks

concentration, descriptive

Secondary/protocol endpoint

PK Parameter: terminal elimination half-life (t1/2) of DNL628 in plasma

Time frame:37 weeks

concentration, descriptive

Other (unclassified)

2 endpoints

Secondary/protocol endpoint/low confidence

PK Parameter: Minimum concentration (Cmin) of DNL628 in plasma

Time frame:37 weeks

concentration, descriptive

Secondary/protocol endpoint/low confidence

PK Parameter: Accumulation ratio of DNL628 in plasma

Time frame:37 weeks

ratio, descriptive

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableno registry results posted yet

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.