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

NCT ID: NCT07328451

Last Updated: 2026-01-14

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 68 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-31
• Study Completion Date: 2027-02-28

Brief 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 biomarker evidence of amyloid positivity.

Conditions

Alzheimer Disease, Early Onset

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Experimental Arm

Group Type: EXPERIMENTAL

DNL628

Intervention Type: DRUG

Multiple ascending doses

Placebo Arm

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Multiple ascending doses

Interventions

DNL628

Multiple ascending doses

Intervention Type: DRUG

Placebo

Multiple ascending doses

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Denali Therapeutics Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Denali Therapeutics

Central Contacts

Clinical Trials at Denali Therapeutics

Role: CONTACT

clinical-trials@dnli.com

Email:

Other Identifiers

2025-523515-11-00

Identifier Type: CTIS

Identifier Source: secondary_id

DNLI-K-0001

Identifier Type: -

Identifier Source: org_study_id