Alzheimer DiseasePhase 1NCT06297590
A First-In-Human Study of LY3954068 in Participants With Early Symptomatic Alzheimer's Disease
A Phase 1 study testing LY3954068 and Flortaucipir F18 in people with Alzheimer Disease, run by Eli Lilly and Company at 10 sites in 3 countries.
Trial summary
The main purpose of this study is to evaluate the safety of LY3954068 in participants with early symptomatic Alzheimer's Disease (AD). The study will also investigate how much LY3954068 gets into the bloodstream and will test the effects of LY3954068 on markers of AD. The study will be comprised of two parts, A and B. Read more about this study
- Who is it for?
- Ages 50 to 85 years
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- LY3954068 and Flortaucipir F18
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 10 sitesin 3 countries
- Study dates
- 15 Aug 2024to Feb 2027
- 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 50 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Have a body mass index (BMI) within the range 18 to 40 kilograms per square meter (kg/m²), inclusive, at screening.
- Have gradual and progressive change in memory function for greater than or equal to (≥) 6 months as reported by the participant or informant.
- Have a mini mental state examination (MMSE) score of 18 to 30 at screening.
- Have a clinical dementia rating (CDR) global score of 0.5 to 1.0, with a memory box score ≥ 0.5 at screening.
- Meet flortaucipir F18 positron emission tomography (PET) criteria, as defined in the TAUVID™ FDA label (TAUVID™ prescribing information, 2024), demonstrating evidence of tau pathology.
- Males who agree to follow contraceptive requirements, or women not of childbearing potential (WNOCBP).
- Participants must have up to 2 study partners who are with contact with the participant at least 10 hours per week and one of whom can attend study appointments.
Who cannot join
- Has current serious or unstable illnesses including cardiovascular, hepatic, renal, gastroenterological, respiratory, endocrinologic, neurologic (other than Alzheimer's Disease), psychiatric, immunologic, or hematologic disease and other conditions that, in the investigator's opinion, could interfere with the analyses in this study; or has a life expectancy of less than (<)24 months.
- Have a sensitivity to flortaucipir F18.
- Have contraindication to magnetic resonance imaging (MRI), including claustrophobia or the presence of contraindicated metal (ferromagnetic) implants/cardiac pacemaker.
- Have a current exposure to an amyloid targeted therapy (ATT). Prior exposure to ATTs greater than 1 year from the last dose may be permitted at the discretion of the investigator and in consultation with the sponsor.
- Have previous exposure to any Investigational Medicinal Product administered intrathecal (IT) or previous exposure to any anti-tau therapy.
- Have a history of clinically significant back pain, back pathology and/or back injury (for example, degenerative disease, spinal deformity or spinal surgery) that may predispose to complications or technical difficulty with lumbar puncture.
Trial locations and contacts
10 sites in 3 countries. Contact the study team or a site near you to ask about taking part.
Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or contact
Physicians interested in becoming principal investigators please contact contact
10 sites in 3 countries
United States6 sites, 6 recruiting
- Not yet recruiting
Massachusetts General Hospital (MGH)
Charlestown, Massachusetts, 02129
617-643-5607
Steven Arnold
- Recruiting
CenExel iResearch, LLC (CenExel iRA)
Decatur, Georgia, 30030
404-537-1281
Kimball Johnson
- Recruiting
Duke University
Durham, North Carolina, 27710
919-684-5196
Shruti Raja
- Recruiting
K2 Medical Research, LLC
Maitland, Florida, 32751
407-500-5252
Brandon Lenox
- Recruiting
Charter Research, LLC
The Villages, Florida, 32162
352-775-1000
Jeffrey Norton
- Recruiting
CenExel AMRI
Toms River, New Jersey, 08755
732-341-9500
Arun Singh
United Kingdom3 sites, 3 recruiting
- Recruiting
National Hospital for Neurology and Neurosurgery (UCLH)
London, WC1N 3BG
0203 448 3011
Catherine Mummery
- Recruiting
Royal Hallamshire Hospital
Sheffield, S10 2JF
0114 2713339
Daniel Blackburn
- Recruiting
University Hospital Southampton
Southampton, SO16 6YD
2381204989
Christopher Kipps
Japan1 site, 1 recruiting
- Recruiting
The University of Tokyo Hospital
Bunkyō City, 113-8655
81120023812
Yoshiki Niimi
About this study
Official title: A Single- and Multiple-Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY3954068 in Patients With Early Symptomatic Alzheimer's Disease
The main purpose of this study is to evaluate the safety of LY3954068 in participants with early symptomatic Alzheimer's Disease (AD). The study will also investigate how much LY3954068 gets into the bloodstream and will test the effects of LY3954068 on markers of AD.
The study will be comprised of two parts, A and B. Each enrolled participant in Part A will receive a single dose of LY3954068 or placebo (no active drug) given into the spinal fluid. Each participant in Part B will receive 2 doses of either LY3954068 or placebo administered into the spinal fluid. Participants will have the opportunity to join an optional bridging period to a separate potential study where participants would receive LY3954068.
The study will last up to approximately 45 weeks for Part A, and 100 weeks for Part B, including the screening period.
- Conditions
- Alzheimer Disease
- Being tested
- LY3954068, Placebo, Flortaucipir F18
- Keywords
- Dementia, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Tauopathies, Tau, Neurodegenerative Diseases, Neurocognitive Disorders, Mental Disorders, Mild Cognitive Impairment
- Medical subject headings
- Alzheimer Disease, Dementia, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Tauopathies, Pick Disease of the Brain, Neurodegenerative Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LY3954068Drug
Administered IT
PlaceboDrug
Administered IT
Flortaucipir F18Drug
Administered intravenously (IV) prior to Positron Emission Tomography (PET) scan
| Study group | Role | What they receive |
|---|---|---|
| LY3954068 (Part A) | Experimental | Single ascending dose of LY3954068 administered intrathecally (IT) Receives: Drug: LY3954068; Drug: Flortaucipir F18 |
| Placebo (Part A) | Placebo comparator | Single ascending dose of placebo administered IT Receives: Drug: Placebo; Drug: Flortaucipir F18 |
| LY3954068 (Part B) | Experimental | Multiple ascending dose of LY3954068 administered IT Receives: Drug: LY3954068; Drug: Flortaucipir F18 |
| Placebo (Part B) | Placebo comparator | Multiple ascending dose of placebo administered IT Receives: Drug: Placebo; Drug: Flortaucipir F18 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part A: Number of participants with one or more Adverse Event (s) (AEs), Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event(s) (SAEs) considered by the investigator to be related to study drug administration
A summary of AEs, TEAEs, SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the reported adverse events module
Measured: Baseline up to Week 24 and Week 72 (for optional bridging period participants)
Part B: Number of participants with one or more Adverse Event (s) (AEs), Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event(s) (SAEs) considered by the investigator to be related to study drug administration
A summary of AEs, TEAEs, SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the reported adverse events module
Measured: Baseline up to Week 52
Secondary outcomes (8)
Part A: Pharmacokinetics (PK): Maximum Observed Concentration (Cmax)
To evaluate plasma concentration of LY3954068
Measured: Day 1 up to Week 24
Part B: PK: Cmax
To evaluate plasma concentration of LY3954068
Measured: Day -1 up to Week 52
Part A: PK: Area Under the Concentration Versus Time Curve (AUC)
To evaluate plasma concentration of LY3954068
Measured: Day 1 up to Week 24
Part B: PK: AUC
To evaluate plasma concentration of LY3954068
Measured: Day -1 up to Week 52
Part A: PK: Cerebrospinal Fluid (CSF) concentration of LY3954068
To evaluate CSF concentration of LY3954068
Measured: Day 3 up to Week 24
Part B: PK: CSF concentration of LY3954068
To evaluate CSF concentration of LY3954068
Measured: Day 3 up to Week 52
Part A: Pharmacodynamics (PD): Change from Baseline of CSF tau
To evaluate the effect of LY3954068 on CSF tau
Measured: Baseline up to Week 24
Part B: PD: Change from Baseline of CSF tau
To evaluate the effect of LY3954068 on CSF tau
Measured: Baseline up to Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2024
- Study start15 Aug 2024
- Primary completionFeb 2027 (estimated)
- Study completionFeb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
- 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Eli Lilly and Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST), Study director, Eli Lilly and Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06297590
- Sponsor's protocol ID
- 18795
- Other IDs
- J4T-MC-OLAA, 2024-510604-37-00, U1111-1302-6222
- Status last verified
- Aug 2026
- First submitted
- 1 Mar 2024
- Last updated
- 24 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single- and Multiple-Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY3954068 in Patients With Early Symptomatic Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT06297590
- Acronym / sponsor ID
- 18795
- Conditions
- Alzheimer Disease
- Keywords
- Dementia, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Tauopathies, Tau, Neurodegenerative Diseases, Neurocognitive Disorders
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- Eli Lilly and CompanyIndustry (pharma, biotech, devices)
- Study start
- 15 Aug 2024 (actual)
- Primary completion
- Feb 2027 (estimated)
- Study completion
- Feb 2027 (estimated)
- First posted
- 7 Mar 2024 (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.
The main purpose of this study is to evaluate the safety of LY3954068 in participants with early symptomatic Alzheimer's Disease (AD). The study will also investigate how much LY3954068 gets into the bloodstream and will test the effects of LY3954068 on markers of AD.
The study will be comprised of two parts, A and B. Each enrolled participant in Part A will receive a single dose of LY3954068 or placebo (no active drug) given into the spinal fluid. Each participant in Part B will receive 2 doses of either LY3954068 or placebo administered into the spinal fluid. Participants will have the opportunity to join an optional bridging period to a separate potential study where participants would receive LY3954068.
The study will last up to approximately 45 weeks for Part A, and 100 weeks for Part B, including the screening period.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| LY3954068 (Part A) | Experimental | Drug: LY3954068, Drug: Flortaucipir F18Single ascending dose of LY3954068 administered intrathecally (IT) |
| Placebo (Part A) | Placebo comparator | Drug: Placebo, Drug: Flortaucipir F18Single ascending dose of placebo administered IT |
| LY3954068 (Part B) | Experimental | Drug: LY3954068, Drug: Flortaucipir F18Multiple ascending dose of LY3954068 administered IT |
| Placebo (Part B) | Placebo comparator | Drug: Placebo, Drug: Flortaucipir F18Multiple ascending dose of placebo administered IT |
Who may qualify
- Ages
- 50 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Have a body mass index (BMI) within the range 18 to 40 kilograms per square meter (kg/m²), inclusive, at screening.
- Have gradual and progressive change in memory function for greater than or equal to (≥) 6 months as reported by the participant or informant.
- Have a mini mental state examination (MMSE) score of 18 to 30 at screening.
- Have a clinical dementia rating (CDR) global score of 0.5 to 1.0, with a memory box score ≥ 0.5 at screening.
- Meet flortaucipir F18 positron emission tomography (PET) criteria, as defined in the TAUVID™ FDA label (TAUVID™ prescribing information, 2024), demonstrating evidence of tau pathology.
Key exclusion criteria (6 listed)
- Has current serious or unstable illnesses including cardiovascular, hepatic, renal, gastroenterological, respiratory, endocrinologic, neurologic (other than Alzheimer's Disease), psychiatric, immunologic, or hematologic disease and other conditions that, in the investigator's opinion, could interfere with the analyses in this study; or has a life expectancy of less than (<)24 months.
- Have a sensitivity to flortaucipir F18.
- Have contraindication to magnetic resonance imaging (MRI), including claustrophobia or the presence of contraindicated metal (ferromagnetic) implants/cardiac pacemaker.
- Have a current exposure to an amyloid targeted therapy (ATT). Prior exposure to ATTs greater than 1 year from the last dose may be permitted at the discretion of the investigator and in consultation with the sponsor.
- Have previous exposure to any Investigational Medicinal Product administered intrathecal (IT) or previous exposure to any anti-tau therapy.
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 |
|---|---|---|
| LY3954068Administered IT | Drug | LY3954068 (Part A), LY3954068 (Part B) |
| PlaceboAdministered IT | Drug | Placebo (Part A), Placebo (Part B) |
| Flortaucipir F18Administered intravenously (IV) prior to Positron Emission Tomography (PET) scan | Drug | LY3954068 (Part A), LY3954068 (Part B), Placebo (Part A), Placebo (Part B) |
Primary outcome
Part A: Number of participants with one or more Adverse Event (s) (AEs), Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event(s) (SAEs) considered by the investigator to be related to study drug administration
Time frame: Baseline up to Week 24 and Week 72 (for optional bridging period participants)
A summary of AEs, TEAEs, SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the reported adverse events module
Part B: Number of participants with one or more Adverse Event (s) (AEs), Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event(s) (SAEs) considered by the investigator to be related to study drug administration
Time frame: Baseline up to Week 52
A summary of AEs, TEAEs, SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the reported adverse events module
8 secondary outcomes
Part A: Pharmacokinetics (PK): Maximum Observed Concentration (Cmax)
Time frame: Day 1 up to Week 24
Part B: PK: Cmax
Time frame: Day -1 up to Week 52
Part A: PK: Area Under the Concentration Versus Time Curve (AUC)
Time frame: Day 1 up to Week 24
Part B: PK: AUC
Time frame: Day -1 up to Week 52
Part A: PK: Cerebrospinal Fluid (CSF) concentration of LY3954068
Time frame: Day 3 up to Week 24
Part B: PK: CSF concentration of LY3954068
Time frame: Day 3 up to Week 52
Part A: Pharmacodynamics (PD): Change from Baseline of CSF tau
Time frame: Baseline up to Week 24
Part B: PD: Change from Baseline of CSF tau
Time frame: Baseline up to Week 52
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 24 Aug 2026.
- A First-In-Human Study of LY3954068 in Participants With Early Symptomatic Alzheimer's DiseaseLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or contact
Physicians interested in becoming principal investigators please contact contact
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST) study director
Eli Lilly and Company
10 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing LY3954068 and Flortaucipir F18 in people with Alzheimer Disease, run by Eli Lilly and Company at 10 sites in 3 countries.
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 7 inclusion and 6 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 24 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 10 sites in United States, United Kingdom, Japan. 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 Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or (1-317-615-4559, LillyTrials@Lilly.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part A: Number of participants with one or more Adverse Event (s) (AEs), Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event(s) (SAEs) considered by the investigator to be related to study drug administration (time frame: Baseline up to Week 24 and Week 72 (for optional bridging period participants)). 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 24 Aug 2026.