DNL628 safety, tolerability, and drug behavior in people 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
This trial will test DNL628 versus placebo in people with early Alzheimer's disease to see if it is safe, well tolerated, and how the body handles the drug.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 68 (estimated) |
| Ages | 18 Years to 75 Years |
| Sex | All |
| Sponsor | Denali Therapeutics Inc. Industry-sponsored |
| Drugs / interventions | immunotherapy |
| Locations | 1 site (London) |
| Trial ID | NCT07328451 on ClinicalTrials.gov |
What this trial studies
This Phase 1b, multicenter, randomized, placebo-controlled, double-blind multiple ascending dose study will enroll adults with early Alzheimer's disease (mild cognitive impairment or mild AD) who have biomarker evidence of amyloid positivity. Participants will receive ascending doses of DNL628 or matching placebo across multiple cohorts to collect safety, tolerability, pharmacokinetic, and pharmacodynamic data. Key eligibility includes a CDR global score of 0.5–1, MMSE 20–30, and confirmed amyloid positivity, with exclusions for significant psychiatric, neurological, or unstable medical conditions. The primary goals are to define a safe dose range and characterize how the drug is absorbed, distributed, metabolized, and excreted, while secondary analyses will look for PD signals.
Who should consider this trial
Good fit: Ideal candidates are adults with early Alzheimer's disease (MCI or mild AD) who are amyloid-positive, have CDR 0.5–1 and MMSE 20–30, meet BMI and weight criteria, and have no unstable medical or psychiatric conditions.
Not a fit: People with advanced AD, non-amyloid dementias, unstable or poorly controlled medical or psychiatric conditions, or those outside the BMI/weight eligibility are unlikely to benefit from participating.
Why it matters
Potential benefit: If successful, DNL628 could advance as a well-tolerated therapy that informs later trials aiming to slow or modify early Alzheimer's disease.
How similar studies have performed: Early-phase safety and PK/PD trials of targeted therapies in early Alzheimer's have been conducted with mixed results, so this approach is experimental but grounded in prior work.
Eligibility criteria
Show full inclusion / exclusion criteria
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
Where this trial is running
London
- Clinical Site(s) — London, United Kingdom (Recruiting)
Study contacts
- Study coordinator: Clinical Trials at Denali Therapeutics
- Email: clinical-trials@dnli.com
- Phone: Email:
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.