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

NCT07758595 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: DNLI-L-0001
• Study Type: interventional
• Target: 178
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a Phase 1/1b, multicenter, randomized, placebo-controlled, double-blind study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single and multiple doses of DNL921 in healthy participants and participants with Alzheimer's disease (AD). The principal aim of this study is to obtain safety and tolerability data. This information, together with PK and PD data, will inform dose selection and design of future studies.

Conditions

Alzheimer's Disease; Healthy Participants

Outcome Measures

Primary Outcomes (2)

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

  46 days

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

  242 days

Secondary Outcomes (10)

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

  Up to 242 Days

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

  Up to 242 Days

• PK Parameter: Area under the concentration-time curve (AUC) from time zero to time of last measurable concentration (AUClast) of DNL921 in serum

  Up to 242 Days

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

  46 Days

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

  Up to 242 Days

Study Arms (2)

Group 1

EXPERIMENTAL

DNL921

Drug: DNL921

Group 2

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

DNL921 DRUG

Single or multiple doses

Group 1

Placebo DRUG

Single or multiple doses matched to experimental treatment

Group 2

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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
• 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

Sponsors & Collaborators

• Denali Therapeutics Inc.: lead

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Medical Monitor

  Denali Therapeutics Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2026
• First Posted: August 11, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): April 1, 2030
• Study Completion (Estimated): April 1, 2030
• Last Updated: August 11, 2026

Record last verified: 2026-08