Alzheimer's DiseasePhase 1NCT07758595
A Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of DNL921 in Healthy Participants and Participants With Alzheimer's Disease
A Phase 1 study testing DNL921 in people with Alzheimer's Disease and Healthy Participants, run by Denali Therapeutics Inc. at 1 site in United Kingdom.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Alzheimer's Disease, Healthy Participants
- What is being tested?
- DNL921
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 178 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 7 Aug 2026to Apr 2030
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
- 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
Show all 12Show fewer
- 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
Who cannot join
- 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
- 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
Show all 10Show fewer
- 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
- Have a positive serum pregnancy test or are currently lactating or breastfeeding
- Have been hospitalized during the 4 weeks prior to screening
- Have had previous anti-amyloid or anti-tau immunotherapy (including active immunization) or have participated in experimental gene therapy or cell therapy at any time
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom1 site, 1 recruiting
- Recruiting
Clinical Site(s)
Manchester
About this study
Official title: A Phase 1/1b, Multicenter, Randomized, Placebo-Controlled, Double-Blind, Single-Dose and Multiple-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL921 in Healthy Participants and Participants With Alzheimer's Disease
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.
Read the detailed description
This clinical trial information was submitted voluntarily under the applicable law and, therefore, certain submission deadlines may not apply. (That is, clinical trial information for this applicable clinical trial was submitted under section 402(j)(4)(A) of the Public Health Service Act and 42 CFR 11.60 and is not subject to the deadlines established by sections 402(j)(2) and (3) of the Public Health Service Act or 42 CFR 11.24 and 11.44.).
- Conditions
- Alzheimer's Disease, Healthy Participants
- Being tested
- DNL921, Placebo
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DNL921Drug
Single or multiple doses
PlaceboDrug
Single or multiple doses matched to experimental treatment
| Study group | Role | What they receive |
|---|---|---|
| Experimental Arm | Experimental | Not described Receives: Drug: DNL921 |
| Placebo Arm | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part A: Incidence and severity of treatment-emergent averse events (TEAEs)
Measured: 46 days
Parts B and C: Incidence and severity of TEAEs in participants with AD
Measured: 242 days
Secondary outcomes (10)
PK Parameter: Maximum concentration (Cmax) of DNL921 in serum
Measured: Up to 242 Days
PK Parameter: Time to reach maximum concentration (tmax) of DNL921 in serum
Measured: 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
Measured: Up to 242 Days
Part A: PK Parameter: AUC from time zero to infinity of DNL921 in serum
Measured: 46 Days
PK Parameter: Elimination half-life (t1/2) of DNL921 in serum
Measured: Up to 242 Days
Parts B and C: PK Parameter: Time to reach minimum concentration (Cmin) of DNL921 in serum
Measured: 242 Days
Parts B and C: PK Parameter: AUC during a dosing interval (AUCtau) of DNL921 in serum
Measured: 242 Days
Parts B and C: PK Parameter: Accumulation ratio of DNL921 in serum
Measured: 242 Days
Parts B and C: Change from baseline in brain amyloid load at Weeks 12 and 28 as measured by amyloid PET scan
Measured: 28 Weeks
Parts B and C: Amyloid clearance at Weeks 12 and 28 as measured by amyloid PET scan
Measured: 28 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Aug 2026
- Study start7 Aug 2026
- Primary completionApr 2030 (estimated)
- Study completionApr 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 178 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Denali Therapeutics Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, Study director, Denali Therapeutics Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07758595
- Sponsor's protocol ID
- DNLI-L-0001
- Status last verified
- Aug 2026
- First submitted
- 6 Aug 2026
- Last updated
- 20 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/1b, Multicenter, Randomized, Placebo-Controlled, Double-Blind, Single-Dose and Multiple-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL921 in Healthy Participants and Participants With Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT07758595
- Acronym / sponsor ID
- DNLI-L-0001
- Conditions
- Alzheimer's Disease, Healthy Participants
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 178 participants (estimated)
- Lead sponsor
- Denali Therapeutics Inc.Industry (pharma, biotech, devices)
- Study start
- 7 Aug 2026 (actual)
- Primary completion
- Apr 2030 (estimated)
- Study completion
- Apr 2030 (estimated)
- First posted
- 11 Aug 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This clinical trial information was submitted voluntarily under the applicable law and, therefore, certain submission deadlines may not apply. (That is, clinical trial information for this applicable clinical trial was submitted under section 402(j)(4)(A) of the Public Health Service Act and 42 CFR 11.60 and is not subject to the deadlines established by sections 402(j)(2) and (3) of the Public Health Service Act or 42 CFR 11.24 and 11.44.).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental Arm | Experimental | Drug: DNL921 |
| Placebo Arm | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
- Are male or female of non-childbearing potential and aged 50 to 75 years at the time of screening
Key exclusion criteria (10 listed)
- 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
- Have other clinically significant neurological or cognitive disorders affecting the CNS, as determined by the investigator, other than AD
- Have specific psychiatric conditions
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DNL921Single or multiple doses | Drug | Experimental Arm |
| PlaceboSingle or multiple doses matched to experimental treatment | Drug | Placebo Arm |
Primary outcome
Part A: Incidence and severity of treatment-emergent averse events (TEAEs)
Time frame: 46 days
Parts B and C: Incidence and severity of TEAEs in participants with AD
Time frame: 242 days
10 secondary outcomes
PK Parameter: Maximum concentration (Cmax) of DNL921 in serum
Time frame: Up to 242 Days
PK Parameter: Time to reach maximum concentration (tmax) of DNL921 in serum
Time frame: 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
Time frame: Up to 242 Days
Part A: PK Parameter: AUC from time zero to infinity of DNL921 in serum
Time frame: 46 Days
PK Parameter: Elimination half-life (t1/2) of DNL921 in serum
Time frame: Up to 242 Days
Parts B and C: PK Parameter: Time to reach minimum concentration (Cmin) of DNL921 in serum
Time frame: 242 Days
Parts B and C: PK Parameter: AUC during a dosing interval (AUCtau) of DNL921 in serum
Time frame: 242 Days
Parts B and C: PK Parameter: Accumulation ratio of DNL921 in serum
Time frame: 242 Days
Parts B and C: Change from baseline in brain amyloid load at Weeks 12 and 28 as measured by amyloid PET scan
Time frame: 28 Weeks
Parts B and C: Amyloid clearance at Weeks 12 and 28 as measured by amyloid PET scan
Time frame: 28 Weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2026.
- Individual participant dataSharing planned: No
Related trials for Alzheimer's Disease
RecruitingPhase 2
Neuroplasticity Enhancement From Cognitive Training Reinforced by Psilocybin
Alzheimer's Disease
Not yet recruiting
Acupressure as Long-term Intervention to Slow the Progression of Early/Mild Alzheimer's Disease
Alzheimer's Disease
RecruitingObservational study
Effectiveness and Safety of Disease-Modifying Therapy for Alzheimer's Disease: A Multicenter Retrospective Study
Alzheimer's Disease (AD)
RecruitingPhase 3
A Phase 3 Study to Evaluate the Safety and Efficacy of KarXT + KarX-EC for the Treatment of Agitation Associated With Alzheimer's Disease (ADAGIO-1)
Alzheimer Disease
RecruitingPhase 3
A Study of Trontinemab in Cognitively Unimpaired Individuals at Risk for Progression to Symptomatic Alzheimer's Disease
Alzheimer's Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Medical Monitor study director
Denali Therapeutics Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing DNL921 in people with Alzheimer's Disease and Healthy Participants, run by Denali Therapeutics Inc. at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 20 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Clinical Trials at Denali Therapeutics (Email:, clinical-trials@dnli.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part A: Incidence and severity of treatment-emergent averse events (TEAEs) (time frame: 46 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2026.