RecruitingPhase 1

A Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of DNL921 in Healthy Participants and Participants With Alzheimer's Disease

A Phase 1/1b, Multicenter, Randomized, Placebo-Controlled, Double-Blind, Single-Dose and Multiple-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL921 in Healthy Participants and Participants With Alzheimer's Disease

Lead sponsor

Denali Therapeutics Inc.

Asset

DNL921

Listed sites

Recruiting sites

Enrollment

178

estimated

Study population

Alzheimer’s disease

Key I/E criterion

•Healthy volunteers

Primary endpoints

•Part•Parts B and C

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

Org study IDDNLI-L-0001

NCT IDNCT07758595

Timeline

Milestones

Study start2026-08-07actual

Study first posted2026-08-11actual

Last update posted2026-08-20actual

Primary completion2030-04estimated (month precision)

Study completion2030-04estimated (month precision)

Assets

Drug assets

DNL921

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age18 Years

Maximum age75 Years

SexAll

Healthy volunteersAccepted

Inclusion criteria

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

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

Endpoints (12)

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)

Amyloid biomarkers

2 endpoints

Secondary/protocol endpoint

Parts B and C: Change from baseline in brain amyloid load at Weeks 12 and 28 as measured by amyloid PET scan

Time frame:28 Weeks

change from baseline, improvement

Secondary/protocol endpoint

Parts B and C: Amyloid clearance at Weeks 12 and 28 as measured by amyloid PET scan

Time frame:28 Weeks

descriptive

Safety / tolerability / PK

6 endpoints

Secondary/protocol endpoint

PK Parameter: Maximum concentration (Cmax) of DNL921 in serum

Time frame:Up to 242 Days

concentration, descriptive

Secondary/protocol endpoint

PK Parameter: Time to reach maximum concentration (tmax) of DNL921 in serum

Time frame:Up to 242 Days

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 DNL921 in serum

Time frame:Up to 242 Days

concentration, descriptive

Secondary/protocol endpoint

Part A: PK Parameter: AUC from time zero to infinity of DNL921 in serum

Time frame:46 Days

concentration, descriptive

Secondary/protocol endpoint

PK Parameter: Elimination half-life (t1/2) of DNL921 in serum

Time frame:Up to 242 Days

concentration, descriptive

Secondary/protocol endpoint

Parts B and C: PK Parameter: AUC during a dosing interval (AUCtau) of DNL921 in serum

Time frame:242 Days

concentration, descriptive

Other (unclassified)

4 endpoints

Primary/protocol endpoint/low confidence

Part A: Incidence and severity of treatment-emergent averse events (TEAEs)

Time frame:46 days

event count, event

Primary/protocol endpoint/low confidence

Parts B and C: Incidence and severity of TEAEs in participants with AD

Time frame:242 days

event count, event

Secondary/protocol endpoint/low confidence

Parts B and C: PK Parameter: Time to reach minimum concentration (Cmin) of DNL921 in serum

Time frame:242 Days

time to event, event

Secondary/protocol endpoint/low confidence

Parts B and C: PK Parameter: Accumulation ratio of DNL921 in serum

Time frame:242 Days

ratio, descriptive

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateNovember 5, 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 November 5, 2026 snapshot.