Alzheimer DiseasePhase 2NCT05063539
A Study of LY3372689 to Assess the Safety, Tolerability, and Efficacy in Participants With Alzheimer's Disease
A Phase 2 study testing LY3372689 in people with Alzheimer Disease, run by Eli Lilly and Company at 69 sites in 5 countries.
Trial summary
The purpose of this study is to assess the safety, tolerability and effect of study drug LY3372689 in participants with early symptomatic Alzheimer's Disease Read more about this study
- Who is it for?
- Ages 60 to 85 years
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- LY3372689
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 327 participants
- Where
- 69 sitesin 5 countries
- Study dates
- 16 Sep 2021to 22 May 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 60 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Gradual and progressive change in memory function reported by participants or informants for ≥ 6 months
- MMSE score of 22 to 30 (inclusive) at screening
- CDR global score of 0.5 to 1.0 (inclusive), with a memory box score ≥0.5.
- Meet 18F flortaucipir positron emission tomography (PET) scan (central analysis) criteria
- Have a study partner who will provide written informed consent to participate
Who cannot join
- Contraindication to MRI or PET scans
- Have known allergies to LY3372689, related compounds, or any components of the formulations
Trial locations and contacts
69 sites in 5 countries.
69 sites in 5 countries
United States35 sites
Abington Neurological Associates, Ltd.
Abington, Pennsylvania, 19001
JEM Research Institute
Atlantis, Florida, 33462
VIN-Julie Schwartzbard
Aventura, Florida, 33180
The Memory Clinic
Bennington, Vermont, 05201-9810
Neurology Offices of South Florida
Boca Raton, Florida, 33428
University at Buffalo - UBMD Neurology
Buffalo, New York, 14203
Hope Clinical Research, Inc.
Canoga Park, California, 91303
Kerwin Medical Center
Dallas, Texas, 75231
Brain Matters Research
Delray Beach, Florida, 33445
Rhode Island Mood & Memory Research Institute
East Providence, Rhode Island, 02914
Neuropsychiatric Research Center of Southwest Florida
Fort Myers, Florida, 33912
Neuro-Pain Medical Center
Fresno, California, 93710
The University of Texas Health Science Center at Houston
Houston, Texas, 77054
Josephson Wallack Munshower Neurology, PC
Indianapolis, Indiana, 46256
Irvine Clinical Research
Irvine, California, 92614
K2 Medical Research
Maitland, Florida, 32751
ClinCloud - Viera
Melbourne, Florida, 32940
Merritt Island Medical Research, LLC
Merritt Island, Florida, 32952
VIN-Andrew Lerman
Miami, Florida, 33133
IMIC, Inc.
Miami, Florida, 33176
VIN-Victor Faradji
Miami, Florida, 33176
Institute for Neurodegenerative Disorders
New Haven, Connecticut, 06510
Suncoast Clinical Research, Inc.
New Port Richey, Florida, 34652
Boston Center for Memory
Newton, Massachusetts, 02459
Renstar Medical Research
Ocala, Florida, 34470
VIN- Margarita Almeida El-Ramey
Pembroke Pines, Florida, 33026
Donald S. Marks M.D., P.C.
Plymouth, Massachusetts, 02360
Keystone Clinical Studies
Plymouth Meeting, Pennsylvania, 19462
Sharp Mesa Vista Hospital
San Diego, California, 92123
The Cognitive and Research Center of New Jersey
Springfield, New Jersey, 07081
Brain Matters Research
Stuart, Florida, 34997
Charter Research - Lady Lake
The Villages, Florida, 32162
Advanced Memory Research Institute of New Jersey
Toms River, New Jersey, 08755
MedVadis Research Corporation
Waltham, Massachusetts, 02451
Adams Clinical
Watertown, Massachusetts, 02472
Australia11 sites
Box Hill Hospital
Box Hill, Victoria, 3128
NeuroCentrix
Carlton, Victoria, 3053
Central Coast Neurosciences Research (Tumbi Umbi)
Central Coast, New South Wales, 2261
Delmont Private Hospital
Glen Iris, Victoria, 3146
HammondCare
Malvern, Victoria, 3144
Private Practice - Dr PL Morris
Southport, Queensland, 4215
St Vincent's Hospital
Sydney, New South Wales, 2010
HammondCare Greenwich Hospital
Sydney, New South Wales, 2065
Hornsby Ku-Ring-Gai Hospital
Sydney, New South Wales, 2077
KARA Institute for Neurological Diseases
Sydney, New South Wales, 2113
The Queen Elizabeth Hospital
Woodville, South Australia, 5011
Japan9 sites
Himeji Central Hospital Affiliated Clinic
Himeji, Hyōgo, 672-8043
Kobe City Medical Center General Hospital
Kobe, Hyōgo, 650-0047
Katayama Medical Clinic
Kurashiki, Okayama-ken, 710-0813
Nozomi Memory Clinic
Mitaka-shi, Tokyo, 181-0013
Kikukawa Clinic
Nerima City, Tokyo, 179-0072
National Center for Geriatrics and Gerontology
Ōbu, Aichi-ken, 4748511
Memory Clinic Ochanomizu
Tokyo, 113-0034
Memory Clinic Toride
Toride, Ibaraki, 302-0004
Oita University Hospital
Yufu, Oita Prefecture, 879-5593
Poland9 sites
Podlaskie Centrum Psychogeriatrii
Bialystok, Podlaskie Voivodeship, 15-756
Centrum Medyczne NEUROMED
Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-163
Centrum Badan Klinicznych PI-House sp. z o.o.
Gdansk, Pomeranian Voivodeship, 80-546
Diamond Clinic
Krakow, Lesser Poland Voivodeship, 31-559
Nzoz Neuro-Kard Ilkowski i Partnerzy SPL
Poznan, Greater Poland Voivodeship, 61-853
Centrum Medyczne SENIOR
Sopot, Pomeranian Voivodeship, 81-855
Centrum Medyczne Euromedis
Szczecin, West Pomeranian Voivodeship, 70-111
Centrum Medyczne NeuroProtect
Warsaw, Masovian Voivodeship, 01-684
Wroclawskie Centrum Alzheimerowskie
Wroclaw, Lower Silesian Voivodeship, 53-203
Canada5 sites
Bruyère Research Institute
Ottawa, Ontario, K1N 5C8
Clinique de la Mémoire de l'Outaouais
Ottawa, Ontario, K1Z 1G3
Ottawa Memory Clinic
Ottawa, Ontario, K1Z 1G3
Diex Recherche Sherbrooke Inc.
Sherbrooke, Quebec, J1L 0H8
Toronto Memory Program
Toronto, Ontario, M3B 2S7
About this study
Official title: Assessment of Safety, Tolerability, and Efficacy of LY3372689 in Early Symptomatic Alzheimer's Disease
The purpose of this study is to assess the safety, tolerability and effect of study drug LY3372689 in participants with early symptomatic Alzheimer's Disease
- Conditions
- Alzheimer Disease
- Being tested
- LY3372689, Placebo
- Keywords
- Dementia, Mild Cognitive Impairment, Prodromal Alzheimer's Disease, Tauopathy, Tau, OGA Inhibitor
- Medical subject headings
- Alzheimer Disease, Dementia, Cognitive Dysfunction, Tauopathies, Pick Disease of the Brain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LY3372689Drug
given orally
LY3372689Drug
given orally
PlaceboDrug
given orally
| Study group | Role | What they receive |
|---|---|---|
| 0.75 Milligram (mg) LY3372689 | Experimental | Double-blind treatment period: Participants received 0.75 mg LY3372689 administered orally once daily for up to 124 weeks.
Post treatment follow up period: Participants who received 0.75 mg LY3372689 during the double-blind treatment period entered a post-treatment follow-up period for 4 weeks after last blinded treatment dose. No study intervention was administered during this period, and participants were followed for safety monitoring.
Post treatment observational extension period: Participants who received 0.75 mg LY3372689 during the double-blind treatment period had the option to enter post-treatment observational extension period for approximately 9 months on average since last blinded treatment dose. No study intervention was administered during this period, and participants were followed for safety, other/exploratory efficacy and biomarker monitoring. Receives: Drug: LY3372689 |
| 3 mg LY3372689 | Experimental | Double-blind treatment period: Participants received 3 mg LY3372689 administered orally once daily for up to 124 weeks.
Post treatment follow up period: Participants who received 3 mg LY3372689 during the double-blind treatment period entered a post-treatment follow-up period for 4 weeks after last blinded treatment dose. No study intervention was administered during this period, and participants were followed for safety monitoring.
Post treatment observational extension period: Participants who received 3 mg LY3372689 during the double-blind treatment period had the option to enter post-treatment observational extension period for approximately 9 months on average since last blinded treatment dose. No study intervention was administered during this period, and participants were followed for safety, other/exploratory efficacy and biomarker monitoring. Receives: Drug: LY3372689 |
| Placebo | Placebo comparator | Double-blind treatment period: Participants received placebo administered orally once daily for up to 124 weeks.
Post treatment follow up period: Participants who received placebo during the double-blind treatment period entered a post-treatment follow-up period for 4 weeks after last blinded treatment dose. No study intervention was administered during this period, and participants were followed for safety monitoring.
Post treatment observational extension period: Participants who received placebo during the double-blind treatment period had the option to enter post-treatment observational extension period for approximately 9 months on average since last blinded treatment dose. No study intervention was administered during this period, and participants were followed for safety, other/exploratory efficacy and biomarker monitoring. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline to End Time Point in Integrated Alzheimer's Disease Rating Scale (iADRS) (Intermediate (Low-medium) Tau Population)
iADRS is a simple linear combination of scores from 13-item alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog13) and the Alzheimer's disease cooperative study-instrumental activities of daily living scale (ADCS-iADL). It is used to assess whether LY3372689 slows down the cognitive and functional decline associated with early symptomatic Alzheimer's Disease, compared to placebo. The iADRS score ranges from 0 to 144 with lower scores indicating worse performance and higher score better performance. Change from baseline was calculated using Bayesian disease progression model (DPM) adjusted for age at baseline, AChEI/Memantine use at baseline, pooled investigator. Data presented are posterior mean with 95% credible interval.
Measured: Baseline, Week 100
Secondary outcomes (14)
Change From Baseline to End Time Point in iADRS (Overall Population)
iADRS is a simple linear combination of scores from 13-item alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog13) and the Alzheimer's disease cooperative study-instrumental activities of daily living scale (ADCS-iADL). It is used to assess whether LY3372689 slows down the cognitive and functional decline associated with early symptomatic Alzheimer's Disease, compared to placebo. The iADRS score ranges from 0 to 144 with lower scores indicating worse performance and higher score better performance. Change from baseline was calculated using Bayesian disease progression model (DPM) adjusted for age at baseline, baseline tau PET category, AChEI/Memantine use at baseline, pooled investigator. Data presented are posterior mean with 95% credible interval.
Measured: Baseline, Week 100
Change From Baseline to End Time Point in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) (Intermediate (Low-medium) Tau Population)
CDR-SB is a semi-structured interview of participants and their caregivers. Participant's cognitive status is rated across 6 domains of functioning, including memory, orientation, judgment/problem solving, community affairs, home/hobbies, and personal care. Severity score are assigned for each of 6 domains; Total score (SB) ranges from 0 to 18. Higher scores indicate greater disease severity. LS Mean change from baseline was calculated using natural cubic spline with 2 degrees of freedom (NCS2) adjusted for fixed effects of NCS basis expansion terms (two terms), NCS basis expansion term-by-treatment interaction, visit (in weeks), investigator site (pooled), age at baseline, AChEI/Memantine use at baseline.
Measured: Baseline, Week 76
Change From Baseline to End Time Point in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) (Overall Population)
CDR-SB is a semi-structured interview of participants and their caregivers. Participant's cognitive status is rated across 6 domains of functioning, including memory, orientation, judgment/problem solving, community affairs, home/hobbies, and personal care. Severity score assigned for each of 6 domains; Total score (SB) ranges from 0 to 18. Higher scores indicate greater disease severity. LS Mean change from baseline was calculated using natural cubic spline with 2 degrees of freedom (NCS2) adjusted for fixed effects of NCS basis expansion terms (two terms), NCS basis expansion term-by-treatment interaction, visit (in weeks), investigator site (pooled), age at baseline, baseline tau PET category, AChEI/Memantine use at baseline.
Measured: Baseline, Week 76
Change From Baseline to End Time Point in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) (Intermediate (Low-medium) Tau Population)
The ADAS-Cog13 is a rater administered instrument that was designed to assess the severity of the dysfunction in the cognitive and noncognitive behaviours characteristic of persons with AD. The cognitive subscale of the ADAS-Cog13 consists of 13 items assessing areas of cognitive function most typically impaired in AD: orientation, verbal memory, language, praxis, delayed free recall, digit cancellation. The ADAS-Cog13 scale ranges from 0 to 85. Higher scores indicate greater disease severity. LS Mean change from baseline was calculated using natural cubic spline with 2 degrees of freedom (NCS2) adjusted for fixed effects of NCS basis expansion terms (two terms), NCS basis expansion term-by-treatment interaction, visit (in weeks), investigator site (pooled), age at baseline, AChEI/Memantine use at baseline.
Measured: Baseline, Week 76
Change From Baseline to End Time Point in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) (Overall Population)
The ADAS-Cog13 is a rater administered instrument that was designed to assess the severity of the dysfunction in the cognitive and noncognitive behaviours characteristic of persons with AD. The cognitive subscale of the ADAS-Cog13 consists of 13 items assessing areas of cognitive function most typically impaired in AD: orientation, verbal memory, language, praxis, delayed free recall, digit cancellation. The ADAS-Cog13 scale ranges from 0 to 85. Higher scores indicate greater disease severity. LS Mean change from baseline was calculated using natural cubic spline with 2 degrees of freedom (NCS2) adjusted for fixed effects of NCS basis expansion terms (two terms), NCS basis expansion term-by-treatment interaction, visit (in weeks), investigator site (pooled), age at baseline, baseline tau PET category, AChEI/Memantine use at baseline.
Measured: Baseline, Week 76
Change From Baseline to End Time Point in Alzheimer's Disease Cooperative Study Instrumental Activities of Daily Living Inventory (ADCS-iADL) (Intermediate (Low-medium) Tau Population)
The ADCS-iADL is a 23-item inventory developed as a rater-administered questionnaire answered by the participant's caregiver. The ADCS-iADL measures both basic and instrumental activities (instrumental activity items 6a, 7-23) of daily living by participants. The range for the ADCS-iADL is 0-59 with higher scores reflecting better performance. LS Mean change from baseline was calculated using natural cubic spline with 2 degrees of freedom (NCS2) adjusted for fixed effects of NCS basis expansion terms (two terms), NCS basis expansion term-by-treatment interaction, visit (in weeks), investigator site (pooled), age at baseline, AChEI/Memantine use at baseline.
Measured: Baseline, Week 76
Change From Baseline to End Time Point in Alzheimer's Disease Cooperative Study Instrumental Activities of Daily Living Inventory (ADCS-iADL) (Overall Population)
The ADCS-iADL is a 23-item inventory developed as a rater-administered questionnaire answered by the participant's caregiver. The ADCS-iADL measures both basic and instrumental activities (instrumental activity items 6a, 7-23) of daily living by participants. The range for the ADCS-iADL is 0-59 with higher scores reflecting better performance. LS Mean change from baseline was calculated using natural cubic spline with 2 degrees of freedom (NCS2) adjusted for fixed effects of NCS basis expansion terms (two terms), NCS basis expansion term-by-treatment interaction, visit (in weeks), investigator site (pooled), age at baseline, baseline tau PET category, AChEI/Memantine use at baseline.
Measured: Baseline, Week 76
Change From Baseline to End Time Point in Mini Mental State Examination (MMSE) (Intermediate (Low-medium) Tau Population)
MMSE is an instrument used to assess cognitive function (orientation, memory, attention, ability to name objects, follow verbal/written commands, write a sentence, and copy figures). Total score ranges from 0 to 30; lower score indicates greater disease severity. LS Mean change from baseline was calculated using natural cubic spline with 2 degrees of freedom (NCS2) adjusted for fixed effects of NCS basis expansion terms (two terms), NCS basis expansion term-by-treatment interaction, visit (in weeks), investigator site (pooled), age at baseline, AChEI/Memantine use at baseline.
Measured: Baseline, Week 76
Change From Baseline to End Time Point in Mini Mental State Examination (MMSE) (Overall Population)
MMSE is an instrument used to assess cognitive function (orientation, memory, attention, ability to name objects, follow verbal/written commands, write a sentence, and copy figures). Total score ranges from 0 to 30; lower score indicates greater disease severity. LS Mean change from baseline was calculated using natural cubic spline with 2 degrees of freedom (NCS2) adjusted for fixed effects of NCS basis expansion terms (two terms), NCS basis expansion term-by-treatment interaction, visit (in weeks), investigator site (pooled), age at baseline, baseline tau PET category, AChEI/Memantine use at baseline.
Measured: Baseline, Week 76
Change From Baseline to End Time Point In Brain Tau Deposition as Measured by Flortaucipir F18 Positron Emission Tomography (PET) Scan (Intermediate (Low-medium) Tau Population)
Flortaucipir PET imaging was used as a quantitative tau biomarker. Quantitative tau burden was formalized using Standardized Uptake Value Ratio (SUVR) from the following composite brain regions: frontal, parietal, occipital, and temporal lobes and the Alzheimer's disease (AD) neocortical signature. The AD neocortical signature region of interest refers to a weighted Alzheimer's Disease specific neocortical region derived from Multiblock Barycentric Discriminant Analysis. Cerebellar gray matter was used as a reference region to derive an SUVr. Larger SUVR reflects larger tau burden. LS Mean change from baseline was calculated using ANCOVA adjusted for baseline score, age and treatment (Type III sum of squares).
Measured: Baseline, Week 76
Change From Baseline to End Time Point In Brain Tau Deposition as Measured by Flortaucipir F18 Positron Emission Tomography (PET) Scan (Overall Population)
Flortaucipir PET imaging was used as a quantitative tau biomarker. Quantitative tau burden was formalized using Standardized Uptake Value Ratio (SUVR) from the following composite brain regions: frontal, parietal, occipital, and temporal lobes and the Alzheimer's disease (AD) neocortical signature. The AD neocortical signature region of interest refers to a weighted Alzheimer's Disease specific neocortical region derived from Multiblock Barycentric Discriminant Analysis. Cerebellar gray matter was used as a reference region to derive an SUVr. Larger SUVR reflects larger tau burden. LS Mean change from baseline was calculated using ANCOVA adjusted for baseline score, baseline tau PET category, age and treatment (Type III sum of squares).
Measured: Baseline, Week 76
Change From Baseline to End Time Point in Volumetric Magnetic Resonance Imaging (vMRI) Measures (Intermediate (Low-medium) Tau Population)
MRI scans at baseline and at 76 weeks after the first treatment were used to quantitatively estimate change in brain atrophy. Volumetric MRI (vMRI) parameters were measured in brain regions: bilateral hippocampus, bilateral whole lateral ventricles, and bilateral whole brain. The atrophy was assessed by tensor-based morphometry, which captures volume changes within the deformation map. LS Mean change from baseline was determined by mixed model repeated measures (MMRM) model with fixed effects of treatment, visit, treatment-by-visit interaction, and adjusted for baseline volume, age at baseline.
Measured: Baseline, Week 76
Change From Baseline to End Time Point in Volumetric Magnetic Resonance Imaging (vMRI) Measures (Overall Population)
MRI scans at baseline and at 76 weeks after the first treatment were used to quantitatively estimate change in brain atrophy. Volumetric MRI (vMRI) parameters were measured in brain regions: bilateral hippocampus, bilateral whole lateral ventricles, and bilateral whole brain. The atrophy was assessed by tensor-based morphometry, which captures volume changes within the deformation map. LS Mean change from baseline was determined by mixed model repeated measures (MMRM) model with fixed effects of treatment, visit, treatment-by-visit interaction, and adjusted for baseline volume, baseline tau PET category, age at baseline.
Measured: Baseline, Week 76
Pharmacokinetics (PK): Plasma Concentrations of LY3372689
Blood samples were measured at week 64 to assess the concentration of LY3372689 in the plasma.
Measured: Week 64: Post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2021
- Study start16 Sep 2021
- Primary completion9 Jul 2024
- Study completion22 May 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Based on a common closed study design. Participants final endpoint time will be between 76-124 weeks.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 327 participants (actual)
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 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Study director, Eli Lilly and Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05063539
- Sponsor's protocol ID
- 18094
- Other IDs
- I9X-MC-MTAE, 2021-000170-29, 2024-512295-36-00
- Status last verified
- May 2026
- First submitted
- 14 Sep 2021
- Last updated
- 12 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
Publications
Fleisher AS, Munsie L, Mancini M, Cheng YJ, Guo J, Nuthall H, Otero DS, Kotari V, Kielbasa W, Hutton M, Brys M, Mergott DJ, Mintun M, Hansson O. Ceperognastat in Early Symptomatic Alzheimer Disease: A Randomized Clinical Trial. JAMA. 2026 Jul 13:e2612768. doi: 10.1001/jama.2026.12768. Online ahead of print.
PubMed 42441396
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of Safety, Tolerability, and Efficacy of LY3372689 in Early Symptomatic Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT05063539
- Acronym / sponsor ID
- 18094
- Conditions
- Alzheimer Disease
- Keywords
- Dementia, Mild Cognitive Impairment, Prodromal Alzheimer's Disease, Tauopathy, Tau, OGA Inhibitor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 327 participants (actual)
- Lead sponsor
- Eli Lilly and CompanyIndustry (pharma, biotech, devices)
- Study start
- 16 Sep 2021 (actual)
- Primary completion
- 9 Jul 2024 (actual)
- Study completion
- 22 May 2025 (actual)
- First posted
- 1 Oct 2021 (actual)
- Results
- Posted 28 Jul 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to assess the safety, tolerability and effect of study drug LY3372689 in participants with early symptomatic Alzheimer's Disease
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
- Model description
- Based on a common closed study design. Participants final endpoint time will be between 76-124 weeks.
| Arm | Type | Receives |
|---|---|---|
| 0.75 Milligram (mg) LY3372689 | Experimental | Drug: LY3372689Double-blind treatment period: Participants received 0.75 mg LY3372689 administered orally once daily for up to 124 weeks. Post treatment follow up period: Participants who received 0.75 mg LY3372689 during the double-blind treatment period entered a post-treatment follow-up period for 4 weeks after last blinded treatment dose. No study intervention was administered during this period, and participants were followed for safety monitoring. Post treatment observational extension period: Participants who received 0.75 mg LY3372689 during the double-blind treatment period had the option to enter post-treatment observational extension period for approximately 9 months on average since last blinded treatment dose. No study intervention was administered during this period, and participants were followed for safety, other/exploratory efficacy and biomarker monitoring. |
| 3 mg LY3372689 | Experimental | Drug: LY3372689Double-blind treatment period: Participants received 3 mg LY3372689 administered orally once daily for up to 124 weeks. Post treatment follow up period: Participants who received 3 mg LY3372689 during the double-blind treatment period entered a post-treatment follow-up period for 4 weeks after last blinded treatment dose. No study intervention was administered during this period, and participants were followed for safety monitoring. Post treatment observational extension period: Participants who received 3 mg LY3372689 during the double-blind treatment period had the option to enter post-treatment observational extension period for approximately 9 months on average since last blinded treatment dose. No study intervention was administered during this period, and participants were followed for safety, other/exploratory efficacy and biomarker monitoring. |
| Placebo | Placebo comparator | Drug: PlaceboDouble-blind treatment period: Participants received placebo administered orally once daily for up to 124 weeks. Post treatment follow up period: Participants who received placebo during the double-blind treatment period entered a post-treatment follow-up period for 4 weeks after last blinded treatment dose. No study intervention was administered during this period, and participants were followed for safety monitoring. Post treatment observational extension period: Participants who received placebo during the double-blind treatment period had the option to enter post-treatment observational extension period for approximately 9 months on average since last blinded treatment dose. No study intervention was administered during this period, and participants were followed for safety, other/exploratory efficacy and biomarker monitoring. |
Who may qualify
- Ages
- 60 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Gradual and progressive change in memory function reported by participants or informants for ≥ 6 months
- MMSE score of 22 to 30 (inclusive) at screening
- CDR global score of 0.5 to 1.0 (inclusive), with a memory box score ≥0.5.
- Meet 18F flortaucipir positron emission tomography (PET) scan (central analysis) criteria
- Have a study partner who will provide written informed consent to participate
Key exclusion criteria (2 listed)
- Contraindication to MRI or PET scans
- Have known allergies to LY3372689, related compounds, or any components of the formulations
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 |
|---|---|---|
| LY3372689given orally | Drug | 0.75 Milligram (mg) LY3372689 |
| LY3372689given orally | Drug | 3 mg LY3372689 |
| Placebogiven orally | Drug | Placebo |
Primary outcome
Change From Baseline to End Time Point in Integrated Alzheimer's Disease Rating Scale (iADRS) (Intermediate (Low-medium) Tau Population)
Time frame: Baseline, Week 100
iADRS is a simple linear combination of scores from 13-item alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog13) and the Alzheimer's disease cooperative study-instrumental activities of daily living scale (ADCS-iADL). It is used to assess whether LY3372689 slows down the cognitive and functional decline associated with early symptomatic Alzheimer's Disease, compared to placebo. The iADRS score ranges from 0 to 144 with lower scores indicating worse performance and higher score better performance. Change from baseline was calculated using Bayesian disease progression model (DPM) adjusted for age at baseline, AChEI/Memantine use at baseline, pooled investigator. Data presented are posterior mean with 95% credible interval.
14 secondary outcomes
Change From Baseline to End Time Point in iADRS (Overall Population)
Time frame: Baseline, Week 100
Change From Baseline to End Time Point in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) (Intermediate (Low-medium) Tau Population)
Time frame: Baseline, Week 76
Change From Baseline to End Time Point in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) (Overall Population)
Time frame: Baseline, Week 76
Change From Baseline to End Time Point in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) (Intermediate (Low-medium) Tau Population)
Time frame: Baseline, Week 76
Change From Baseline to End Time Point in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) (Overall Population)
Time frame: Baseline, Week 76
Change From Baseline to End Time Point in Alzheimer's Disease Cooperative Study Instrumental Activities of Daily Living Inventory (ADCS-iADL) (Intermediate (Low-medium) Tau Population)
Time frame: Baseline, Week 76
Change From Baseline to End Time Point in Alzheimer's Disease Cooperative Study Instrumental Activities of Daily Living Inventory (ADCS-iADL) (Overall Population)
Time frame: Baseline, Week 76
Change From Baseline to End Time Point in Mini Mental State Examination (MMSE) (Intermediate (Low-medium) Tau Population)
Time frame: Baseline, Week 76
Change From Baseline to End Time Point in Mini Mental State Examination (MMSE) (Overall Population)
Time frame: Baseline, Week 76
Change From Baseline to End Time Point In Brain Tau Deposition as Measured by Flortaucipir F18 Positron Emission Tomography (PET) Scan (Intermediate (Low-medium) Tau Population)
Time frame: Baseline, Week 76
Change From Baseline to End Time Point In Brain Tau Deposition as Measured by Flortaucipir F18 Positron Emission Tomography (PET) Scan (Overall Population)
Time frame: Baseline, Week 76
Change From Baseline to End Time Point in Volumetric Magnetic Resonance Imaging (vMRI) Measures (Intermediate (Low-medium) Tau Population)
Time frame: Baseline, Week 76
Change From Baseline to End Time Point in Volumetric Magnetic Resonance Imaging (vMRI) Measures (Overall Population)
Time frame: Baseline, Week 76
Pharmacokinetics (PK): Plasma Concentrations of LY3372689
Time frame: Week 64: Post-dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42441396Fleisher AS, Munsie L, Mancini M, Cheng YJ, Guo J, Nuthall H, Otero DS, Kotari V, Kielbasa W, Hutton M, Brys M, Mergott DJ, Mintun M, Hansson O. Ceperognastat in Early Symptomatic Alzheimer Disease: A Randomized Clinical Trial. JAMA. 2026 Jul 13:e2612768. doi: 10.1001/jama.2026.12768. Online ahead of print.
- A Study of LY3372689 to Assess the Safety, Tolerability, and Efficacy in Participants With Alzheimer's DiseaseLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
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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. This study is not recruiting at the moment.
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) study director
Eli Lilly and Company
69 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing LY3372689 in people with Alzheimer Disease, run by Eli Lilly and Company at 69 sites in 5 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 5 inclusion and 2 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: finished, as of the sponsor's last update on 12 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 69 sites in United States, Australia, Japan, Poland, Canada. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline to End Time Point in Integrated Alzheimer's Disease Rating Scale (iADRS) (Intermediate (Low-medium) Tau Population) (time frame: Baseline, Week 100). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05063539, which also lists 1 linked publication.
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 12 Jun 2026.