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

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL628 in Participants With Early Alzheimer's Disease (NCT07328451) is a Phase 1 interventional studying Alzheimer Disease, Early Onset, sponsored by Denali Therapeutics Inc.. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

About This Trial

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.

What Stage of Research Is This?

Phase 1 trials test a new treatment for the first time in humans, focusing on safety, dosing, and how the body processes the drug. For Alzheimer Disease, Early Onset, a Phase 1 study typically enrolls a small number of participants — often healthy volunteers or patients who have exhausted standard treatment options. Phase 1 results determine whether a treatment moves into larger Phase 2 efficacy studies.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

Target enrollment of 68 participants puts this in the typical range for a Phase 2-style efficacy study or a moderate Phase 3 trial in a focused Alzheimer Disease, Early Onset subpopulation. At this scale, the study has enough statistical power to detect a clear treatment effect but is not the largest cohort in the field.

Who May Be Eligible (Plain English)

Key Who May Qualify: - 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) Key Who Should NOT Join This Trial: - 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 Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language

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) Key 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

Treatments Being Tested

DRUG

DNL628

Multiple ascending doses

DRUG

Placebo

Multiple ascending doses

Locations (1)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

Clinical Site(s)

London, United Kingdom

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT07328451), the sponsor (Denali Therapeutics Inc.), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT07328451 clinical trial studying?

Who can participate in NCT07328451?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT07328451?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT07328451. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT07328451. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.