NCT07328451

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
68

participants targeted

Target at P75+ for phase_1

Timeline
9mo left

Started Jan 2026

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress21%
Jan 2026Feb 2027

First Submitted

Initial submission to the registry

December 24, 2025

Completed
16 days until next milestone

First Posted

Study publicly available on registry

January 9, 2026

Completed
21 days until next milestone

Study Start

First participant enrolled

January 30, 2026

Completed
1 year until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2027

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2027

Last Updated

February 23, 2026

Status Verified

February 1, 2026

Enrollment Period

1 year

First QC Date

December 24, 2025

Last Update Submit

February 20, 2026

Conditions

Alzheimer Disease, Early Onset

Keywords

Alzheimer's Disease

Outcome Measures

Primary Outcomes (1)

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

    37 weeks

Secondary Outcomes (8)

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

    37 weeks

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

    37 weeks

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

    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

    37 weeks

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

    37 weeks

  • +3 more secondary outcomes

Study Arms (2)

Experimental Arm

EXPERIMENTAL
Drug: DNL628

Placebo Arm

PLACEBO COMPARATOR
Drug: Placebo

Interventions

DNL628DRUG

Multiple ascending doses

Experimental Arm
PlaceboDRUG

Multiple ascending doses

Placebo Arm

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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)

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Clinical Site(s)

London, WC1N 3BG, United Kingdom

RECRUITING

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

DementiaBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesTauopathiesNeurodegenerative DiseasesNeurocognitive DisordersMental Disorders

Study Officials

  • Medical Monitor

    Denali Therapeutics

    STUDY DIRECTOR

Central Study Contacts

Clinical Trials at Denali Therapeutics

CONTACT

Email:clinical-trials@dnli.com

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Masking Details
Sponsor staff directly interacting with the site (clinical operations and medical monitor) will be blinded but may be unblinded if necessary to ensure participant safety.
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 24, 2025

First Posted

January 9, 2026

Study Start

January 30, 2026

Primary Completion (Estimated)

February 1, 2027

Study Completion (Estimated)

February 1, 2027

Last Updated

February 23, 2026

Record last verified: 2026-02

Data Sharing

IPD Sharing
Will not share

Locations

GB(1)