← Trials/Trial dossier/NCT05063539

CompletedPhase 2Results posted

A Study of LY3372689 to Assess the Safety, Tolerability, and Efficacy in Participants With Alzheimer's Disease

Assessment of Safety, Tolerability, and Efficacy of LY3372689 in Early Symptomatic Alzheimer's Disease

Lead sponsor

Eli Lilly and Company

Asset

LY3372689

Listed sites

Recruiting sites

Enrollment

327

actual

Study population

Alzheimer’s disease

Key I/E criteria

•CDR global 0.5-1•MMSE 22-30•Study partner/caregiver required•MRI contraindications excluded

Primary endpoint

•ADAS-Cog

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Org study ID18094

Eudract number2021-000170-29

Ctis2024-512295-36-00

Secondary IDI9X-MC-MTAEEli Lilly and Company

NCT IDNCT05063539

Timeline

Milestones

Study start2021-09-16actual

Study first posted2021-10-01actual

Primary completion2024-07-09actual

Study completion2025-05-22actual

Results first posted2025-07-28actual

Last update posted2026-06-12actual

Assets

Drug assets

LY3372689

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age60 Years

Maximum age85 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•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

Exclusion criteria

•Contraindication to MRI or PET scans

•Have known allergies to LY3372689, related compounds, or any components of the formulations

Endpoints (30)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Global cognition

Function / daily living

Tau biomarkers

Neuroimaging

Safety / tolerability / PK

Global cognition

12 endpoints

Secondary/protocol endpoint

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

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline to End Time Point in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) (Overall Population)

Time frame:Baseline, Week 76

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Secondary/registry result

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

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), score on a scale	Standard error
0.75mg LY3372689n=84 Participants	0.91	0.23
3 mg LY3372689n=80 Participants	2.14	0.24
Placebon=84 Participants	1.05	0.22

LS Mean Difference-0.1495% CI-0.763 - 0.488p0.665NCS2

LS Mean Difference1.0995% CI0.435 - 1.736p0.001NCS2

Secondary/protocol endpoint

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

ADAS-Cog

change from baseline, improvement

Secondary/registry result

Change From Baseline to End Time Point in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) (Overall Population)

Time frame:Baseline, Week 76

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), score on a scale	Standard error
0.75mg LY3372689n=106 Participants	1.54	0.25
3 mg LY3372689n=101 Participants	2.81	0.27
Placebon=106 Participants	1.48	0.25

LS Mean Difference0.0595% CI-0.641 - 0.749p0.878NCS2

LS Mean Difference1.3395% CI0.615 - 2.050p<0.001NCS2

Secondary/protocol endpoint

Change From Baseline to End Time Point in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) (Overall Population)

Time frame:Baseline, Week 76

ADAS-Cog

change from baseline, improvement

Secondary/registry result

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

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), score on a scale	Standard error
0.75mg LY3372689n=84 Participants	4.00	0.70
3 mg LY3372689n=80 Participants	4.91	0.76
Placebon=84 Participants	5.14	0.69

LS Mean Difference-1.1395% CI-3.073 - 0.811p0.252NCS2

LS Mean Difference-0.2395% CI-2.252 - 1.797p0.825NCS2

Secondary/registry result

Change From Baseline to End Time Point in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) (Overall Population)

Time frame:Baseline, Week 76

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), score on a scale	Standard error
0.75mg LY3372689n=106 Participants	5.58	0.78
3 mg LY3372689n=102 Participants	7.61	0.83
Placebon=106 Participants	5.95	0.76

LS Mean Difference-0.3795% CI-2.527 - 1.779p0.733NCS2

LS Mean Difference1.6695% CI-0.565 - 3.877p0.143NCS2

Secondary/protocol endpoint

Change From Baseline to End Time Point in Mini Mental State Examination (MMSE) (Intermediate (Low-medium) Tau Population)

Time frame:Baseline, Week 76

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline to End Time Point in Mini Mental State Examination (MMSE) (Overall Population)

Time frame:Baseline, Week 76

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Secondary/registry result

Change From Baseline to End Time Point in Mini Mental State Examination (MMSE) (Intermediate (Low-medium) Tau Population)

Time frame:Baseline, Week 76

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), score on a scale	Standard error
0.75mg LY3372689n=84 Participants	-1.65	0.38
3 mg LY3372689n=80 Participants	-2.79	0.41
Placebon=84 Participants	-2.25	0.37

LS Mean Difference0.6095% CI-0.445 - 1.642p0.259NCS2

LS Mean Difference-0.5495% CI-1.629 - 0.541p0.324NCS2

Secondary/registry result

Change From Baseline to End Time Point in Mini Mental State Examination (MMSE) (Overall Population)

Time frame:Baseline, Week 76

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), score on a scale	Standard error
0.75mg LY3372689n=106 Participants	-2.52	0.41
3 mg LY3372689n=102 Participants	-4.00	0.44
Placebon=106 Participants	-2.70	0.40

LS Mean Difference0.1895% CI-0.946 - 1.313p0.749NCS2

LS Mean Difference-1.3095% CI-2.462 - -0.134p0.029NCS2

Function / daily living

8 endpoints

Primary/protocol endpoint

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

ADAS-Cog

change from baseline, improvement

Primary/registry result

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

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Reported bounds
0.75 mg LY3372689n=86 Participants	NA	-NA - NA
3 mg LY3372689n=85 Participants	NA	-NA - NA
Placebon=84 Participants	NA	-NA - NA

Posterior Mean Difference1.6895% CI-0.375 - 3.771

Posterior Mean Difference-3.2095% CI-5.354 - -1.042

Secondary/protocol endpoint

Change From Baseline to End Time Point in iADRS (Overall Population)

Time frame:Baseline, Week 100

ADAS-Cog

change from baseline, improvement

Secondary/registry result

Change From Baseline to End Time Point in iADRS (Overall Population)

Time frame:Baseline, Week 100

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Reported bounds
0.75 mg LY3372689n=109 Participants	NA	-NA - NA
3 mg LY3372689n=108 Participants	NA	-NA - NA
Placebon=106 Participants	NA	-NA - NA

Posterior Mean Difference1.5995% CI-0.443 - 3.697

Posterior Mean Difference-5.0795% CI-7.277 - -2.862

Secondary/protocol endpoint

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, improvement

Secondary/protocol endpoint

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, improvement

Secondary/registry result

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, improvement

Posted result

Group	Value (least_squares_mean), score on a scale	Standard error
0.75mg LY3372689n=83 Participants	-2.65	0.72
3 mg LY3372689n=79 Participants	-5.34	0.77
Placebon=82 Participants	-2.82	0.70

LS Mean Difference0.1895% CI-1.802 - 2.158p0.860NCS2

LS Mean Difference-2.5195% CI-4.567 - -0.456p0.017NCS2

Secondary/registry result

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, improvement

Posted result

Group	Value (least_squares_mean), score on a scale	Standard error
0.75mg LY3372689n=105 Participants	-4.02	0.79
3 mg LY3372689n=101 Participants	-7.26	0.83
Placebon=104 Participants	-3.24	0.77

LS Mean Difference-0.7895% CI-2.949 - 1.387p0.479NCS2

LS Mean Difference-4.0195% CI-6.239 - -1.788p<0.001NCS2

Tau biomarkers

6 endpoints

Secondary/protocol endpoint

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, improvement

Secondary/protocol endpoint

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, improvement

Secondary/registry result

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, improvement

Posted result

Group	Value (least_squares_mean), standardized uptake value ratio (SUVR)	Standard error
0.75mg LY3372689Frontaln=68 Participants	0.05	0.008
Parietaln=68 Participants	0.05	0.009
Lateral occipitaln=68 Participants	0.04	0.015
Lateral temporaln=68 Participants	0.07	0.011
AD neocortical signature (measured using MUBADA)n=68 Participants	0.07	0.011
3 mg LY3372689Frontaln=57 Participants	0.03	0.009
Parietaln=57 Participants	0.03	0.010
Lateral occipitaln=57 Participants	0.05	0.016
Lateral temporaln=57 Participants	0.04	0.012
AD neocortical signature (measured using MUBADA)n=57 Participants	0.05	0.012
PlaceboFrontaln=70 Participants	0.04	0.008
Parietaln=70 Participants	0.06	0.009
Lateral occipitaln=70 Participants	0.07	0.015
Lateral temporaln=70 Participants	0.07	0.011
AD neocortical signature (measured using MUBADA)n=70 Participants	0.08	0.010

LS Mean Difference0.0195% CI-0.01 - 0.03p0.346ANCOVA

Frontal

LS Mean Difference-0.0195% CI-0.04 - 0.01p0.412ANCOVA

Frontal

LS Mean Difference-0.0195% CI-0.04 - 0.02p0.421ANCOVA

Parietal

LS Mean Difference-0.0295% CI-0.05 - 0.00p0.080ANCOVA

Parietal

LS Mean Difference-0.0395% CI-0.07 - 0.01p0.192ANCOVA

Lateral occipital

LS Mean Difference-0.0295% CI-0.07 - 0.02p0.279ANCOVA

Lateral occipital

LS Mean Difference-0.0195% CI-0.04 - 0.02p0.693ANCOVA

Lateral temporal

LS Mean Difference-0.0395% CI-0.07 - -0.00p0.040ANCOVA

Lateral temporal

LS Mean Difference-0.0095% CI-0.03 - 0.03p0.838ANCOVA

AD neocortical signature (measured using MUBADA)

LS Mean Difference-0.0395% CI-0.06 - 0.00p0.055ANCOVA

AD neocortical signature (measured using MUBADA)

Secondary/registry result

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, improvement

Posted result

Group	Value (least_squares_mean), SUVR	Standard error
0.75mg LY3372689Frontaln=79 Participants	0.07	0.011
Parietaln=79 Participants	0.08	0.013
Lateral occipitaln=79 Participants	0.08	0.018
Lateral temporaln=79 Participants	0.08	0.015
AD neocortical signature (measured using MUBADA)n=79 Participants	0.09	0.014
3 mg LY3372689Frontaln=70 Participants	0.06	0.011
Parietaln=70 Participants	0.08	0.013
Lateral occipitaln=70 Participants	0.09	0.018
Lateral temporaln=70 Participants	0.07	0.015
AD neocortical signature (measured using MUBADA)n=70 Participants	0.08	0.015
PlaceboFrontaln=86 Participants	0.06	0.011
Parietaln=86 Participants	0.07	0.012
Lateral occipitaln=86 Participants	0.09	0.017
Lateral temporaln=86 Participants	0.08	0.014
AD neocortical signature (measured using MUBADA)n=86 Participants	0.09	0.014

LS Mean Difference0.0195% CI-0.02 - 0.04p0.455ANCOVA

Frontal

LS Mean Difference-0.0095% CI-0.03 - 0.02p0.745ANCOVA

Frontal

LS Mean Difference0.0195% CI-0.02 - 0.04p0.676ANCOVA

Parietal

LS Mean Difference0.0095% CI-0.03 - 0.03p0.794ANCOVA

Parietal

LS Mean Difference-0.0195% CI-0.05 - 0.03p0.643ANCOVA

Lateral occipital

LS Mean Difference-0.0095% CI-0.05 - 0.04p0.880ANCOVA

Lateral occipital

LS Mean Difference-0.0095% CI-0.04 - 0.03p0.844ANCOVA

Lateral temporal

LS Mean Difference-0.0195% CI-0.05 - 0.02p0.388ANCOVA

LS Mean Difference0.0095% CI-0.03 - 0.04p0.815ANCOVA

AD neocortical signature (measured using MUBADA)

LS Mean Difference-0.0195% CI-0.04 - 0.02p0.562ANCOVA

AD neocortical signature (measured using MUBADA)

Secondary/protocol endpoint

Change From Baseline to End Time Point in Volumetric Magnetic Resonance Imaging (vMRI) Measures (Overall Population)

Time frame:Baseline, Week 76

change from baseline, improvement

Secondary/registry result

Change From Baseline to End Time Point in Volumetric Magnetic Resonance Imaging (vMRI) Measures (Overall Population)

Time frame:Baseline, Week 76

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), cm^3	Standard error
0.75mg LY3372689Bilateral Hippocampusn=82 Participants	-0.21	0.018
Bilateral Whole Lateral Ventriclesn=82 Participants	4.95	0.444
Bilateral Whole Brainn=82 Participants	-15.61	1.292
3 mg LY3372689Bilateral Hippocampusn=78 Participants	-0.17	0.018
Bilateral Whole Lateral Ventriclesn=78 Participants	5.74	0.455
Bilateral Whole Brainn=78 Participants	-14.62	1.313
PlaceboBilateral Hippocampusn=94 Participants	-0.29	0.017
Bilateral Whole Lateral Ventriclesn=94 Participants	7.16	0.409
Bilateral Whole Brainn=94 Participants	-22.78	1.195

LS Mean Difference0.0895% CI0.04 - 0.13p<0.001Mixed Models Analysis

Bilateral Hippocampus

LS Mean Difference0.1295% CI0.08 - 0.17p<0.001Mixed Models Analysis

LS Mean Difference-2.2195% CI-3.33 - -1.08p<0.001Mixed Models Analysis

Bilateral Whole Lateral Ventricles

LS Mean Difference-1.4295% CI-2.57 - -0.28p0.015Mixed Models Analysis

Bilateral Whole Lateral Ventricles

LS Mean Difference7.1795% CI3.95 - 10.40p<0.001Mixed Models Analysis

Bilateral Whole Brain

LS Mean Difference8.1695% CI4.85 - 11.47p<0.001Mixed Models Analysis

Bilateral Whole Brain

Neuroimaging

2 endpoints

Secondary/protocol endpoint

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, improvement

Secondary/registry result

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, improvement

Posted result

Group	Value (least_squares_mean), cubic centimeter (cm^3)	Standard error
0.75mg LY3372689Bilateral Hippocampusn=68 Participants	-0.19	0.017
Bilateral Whole Lateral Ventriclesn=68 Participants	3.52	0.425
Bilateral Whole Brainn=68 Participants	-10.75	1.231
3 mg LY3372689Bilateral Hippocampusn=61 Participants	-0.16	0.019
Bilateral Whole Lateral Ventriclesn=61 Participants	4.25	0.458
Bilateral Whole Brainn=61 Participants	-9.56	1.345
PlaceboBilateral Hippocampusn=75 Participants	-0.28	0.016
Bilateral Whole Lateral Ventriclesn=75 Participants	5.89	0.405
Bilateral Whole Brainn=75 Participants	-18.92	1.186

LS Mean Difference0.0995% CI0.04 - 0.14p<0.001Mixed Models Analysis

Bilateral Hippocampus

LS Mean Difference0.1395% CI0.08 - 0.18p<0.001Mixed Models Analysis

Bilateral Hippocampus

LS Mean Difference-2.3795% CI-3.53 - -1.21p<0.001Mixed Models Analysis

Bilateral Whole Lateral Ventricles

LS Mean Difference-1.6495% CI-2.84 - -0.43p0.008Mixed Models Analysis

Bilateral Whole Lateral Ventricles

LS Mean Difference8.1795% CI4.79 - 11.56p<0.001Mixed Models Analysis

Bilateral Whole Brain

LS Mean Difference9.3795% CI5.81 - 12.92p<0.001Mixed Models Analysis

Bilateral Whole Brain

Safety / tolerability / PK

2 endpoints

Secondary/protocol endpoint

Pharmacokinetics (PK): Plasma Concentrations of LY3372689

Time frame:Week 64: Post-dose

concentration, descriptive

Secondary/registry result

Pharmacokinetics (PK): Plasma Concentrations of LY3372689

Time frame:Week 64: Post-dose

concentration, descriptive

Posted result

Group	Value (geometric_mean), nanograms per milliliter (ng/mL)	Geometric coefficient of variation
0.75 mg LY3372689n=76 Participants	3.95	163
3 mg LY3372689n=69 Participants	12.9	212

Publications (1)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

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. doi: 10.1001/jama.2026.12768. Online ahead of print.
PMID42441396via DERIVED

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.