A Study of LY3372689 to Assess the Safety, Tolerability,... | NCT05063539 | Trialant
NCT05063539
Sponsor
Eli Lilly and Company
Status
Completed
Last Update Posted
Jun 12, 2026Actual
Enrollment
327Actual
Phase
Phase 2
Conditions
Alzheimer Disease
Interventions
LY3372689
LY3372689
Placebo
Countries
United States
Australia
Canada
Japan
Poland
Protocol Section
Identification Module
NCT ID
NCT05063539
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
18094
Secondary IDs
ID
Type
Description
Link
I9X-MC-MTAE
Other Identifier
Eli Lilly and Company
2021-000170-29
EudraCT Number
2024-512295-36-00
EU Trial (CTIS) Number
Brief Title
A Study of LY3372689 to Assess the Safety, Tolerability, and Efficacy in Participants With Alzheimer's Disease
Official Title
Assessment of Safety, Tolerability, and Efficacy of LY3372689 in Early Symptomatic Alzheimer's Disease
Acronym
Not provided
Organization
Eli Lilly and CompanyINDUSTRY
Status Module
Record Verification Date
May 2026
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Sep 16, 2021Actual
Primary Completion Date
Jul 9, 2024Actual
Completion Date
May 22, 2025Actual
First Submitted Date
Sep 14, 2021
First Submission Date that Met QC Criteria
Sep 29, 2021
First Posted Date
Oct 1, 2021Actual
Results Waived
Not provided
Results First Submitted Date
Jul 9, 2025
Results First Submitted that Met QC Criteria
Jul 9, 2025
Results First Posted Date
Jul 28, 2025Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
May 19, 2026
Last Update Posted Date
Jun 12, 2026Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Eli Lilly and CompanyINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief 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
Detailed Description
Not provided
Conditions Module
Conditions
Alzheimer Disease
Keywords
Dementia
Mild Cognitive Impairment
Prodromal Alzheimer's Disease
Tauopathy
Tau
OGA Inhibitor
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
327Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
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.
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.
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.
Interventions
Name
Type
Description
Arm Group Labels
Other Names
LY3372689
Drug
given orally
0.75 Milligram (mg) LY3372689
LY3372689
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
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.
Baseline, Week 100
Secondary Outcomes
Measure
Description
Time Frame
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.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
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.
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.
Types
Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame
Data are available 6 months after the primary publication and approval of the indication studied in the US and European Union (EU), whichever is later. Data will be indefinitely available for requesting.
Access Criteria
A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
The study consists of a double-blind treatment period with a 124-week (wk) duration followed by a post treatment follow-up (PTFU) period for 4 weeks after last blinded treatment dose and Post treatment observational extension (PTOE) period for approximately 9 months on average since last blinded treatment dose.
Recruitment Details
Not provided
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
0.75 Milligram (mg) LY3372689
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.
Periods
Title
Milestones
Reasons Not Completed
Double-Blind Treatment Period
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol
Aug 22, 2024
May 18, 2026
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Netherlands
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
No data available
No data is available for this block.
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Based on a common closed study design. Participants final endpoint time will be between 76-124 weeks.
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Double
Masking Description
Not provided
Who Masked
ParticipantInvestigator
Drug: Placebo
Drug
given orally
3 mg LY3372689
Placebo
Drug
given orally
Placebo
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.
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.
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.
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.
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.
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.
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.
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.
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).
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).
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.
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.
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.
Week 64: Post-dose
Fresno
California
93710
United States
Irvine Clinical Research
Irvine
California
92614
United States
Sharp Mesa Vista Hospital
San Diego
California
92123
United States
Institute for Neurodegenerative Disorders
New Haven
Connecticut
06510
United States
JEM Research Institute
Atlantis
Florida
33462
United States
VIN-Julie Schwartzbard
Aventura
Florida
33180
United States
Neurology Offices of South Florida
Boca Raton
Florida
33428
United States
Brain Matters Research
Delray Beach
Florida
33445
United States
Neuropsychiatric Research Center of Southwest Florida
Fort Myers
Florida
33912
United States
K2 Medical Research
Maitland
Florida
32751
United States
ClinCloud - Viera
Melbourne
Florida
32940
United States
Merritt Island Medical Research, LLC
Merritt Island
Florida
32952
United States
VIN-Andrew Lerman
Miami
Florida
33133
United States
IMIC, Inc.
Miami
Florida
33176
United States
VIN-Victor Faradji
Miami
Florida
33176
United States
Suncoast Clinical Research, Inc.
New Port Richey
Florida
34652
United States
Renstar Medical Research
Ocala
Florida
34470
United States
VIN- Margarita Almeida El-Ramey
Pembroke Pines
Florida
33026
United States
Brain Matters Research
Stuart
Florida
34997
United States
Charter Research - Lady Lake
The Villages
Florida
32162
United States
Josephson Wallack Munshower Neurology, PC
Indianapolis
Indiana
46256
United States
Boston Center for Memory
Newton
Massachusetts
02459
United States
Donald S. Marks M.D., P.C.
Plymouth
Massachusetts
02360
United States
MedVadis Research Corporation
Waltham
Massachusetts
02451
United States
Adams Clinical
Watertown
Massachusetts
02472
United States
The Cognitive and Research Center of New Jersey
Springfield
New Jersey
07081
United States
Advanced Memory Research Institute of New Jersey
Toms River
New Jersey
08755
United States
University at Buffalo - UBMD Neurology
Buffalo
New York
14203
United States
Abington Neurological Associates, Ltd.
Abington
Pennsylvania
19001
United States
Keystone Clinical Studies
Plymouth Meeting
Pennsylvania
19462
United States
Rhode Island Mood & Memory Research Institute
East Providence
Rhode Island
02914
United States
Kerwin Medical Center
Dallas
Texas
75231
United States
The University of Texas Health Science Center at Houston
Houston
Texas
77054
United States
The Memory Clinic
Bennington
Vermont
05201-9810
United States
Central Coast Neurosciences Research (Tumbi Umbi)
Central Coast
New South Wales
2261
Australia
St Vincent's Hospital
Sydney
New South Wales
2010
Australia
HammondCare Greenwich Hospital
Sydney
New South Wales
2065
Australia
Hornsby Ku-Ring-Gai Hospital
Sydney
New South Wales
2077
Australia
KARA Institute for Neurological Diseases
Sydney
New South Wales
2113
Australia
Private Practice - Dr PL Morris
Southport
Queensland
4215
Australia
The Queen Elizabeth Hospital
Woodville
South Australia
5011
Australia
Box Hill Hospital
Box Hill
Victoria
3128
Australia
NeuroCentrix
Carlton
Victoria
3053
Australia
Delmont Private Hospital
Glen Iris
Victoria
3146
Australia
HammondCare
Malvern
Victoria
3144
Australia
Bruyère Research Institute
Ottawa
Ontario
K1N 5C8
Canada
Clinique de la Mémoire de l'Outaouais
Ottawa
Ontario
K1Z 1G3
Canada
Ottawa Memory Clinic
Ottawa
Ontario
K1Z 1G3
Canada
Toronto Memory Program
Toronto
Ontario
M3B 2S7
Canada
Diex Recherche Sherbrooke Inc.
Sherbrooke
Quebec
J1L 0H8
Canada
National Center for Geriatrics and Gerontology
Ōbu
Aichi-ken
4748511
Japan
Himeji Central Hospital Affiliated Clinic
Himeji
Hyōgo
672-8043
Japan
Kobe City Medical Center General Hospital
Kobe
Hyōgo
650-0047
Japan
Memory Clinic Toride
Toride
Ibaraki
302-0004
Japan
Oita University Hospital
Yufu
Oita Prefecture
879-5593
Japan
Katayama Medical Clinic
Kurashiki
Okayama-ken
710-0813
Japan
Nozomi Memory Clinic
Mitaka-shi
Tokyo
181-0013
Japan
Kikukawa Clinic
Nerima City
Tokyo
179-0072
Japan
Memory Clinic Ochanomizu
Tokyo
113-0034
Japan
Nzoz Neuro-Kard Ilkowski i Partnerzy SPL
Poznan
Greater Poland Voivodeship
61-853
Poland
Centrum Medyczne NEUROMED
Bydgoszcz
Kuyavian-Pomeranian Voivodeship
85-163
Poland
Diamond Clinic
Krakow
Lesser Poland Voivodeship
31-559
Poland
Wroclawskie Centrum Alzheimerowskie
Wroclaw
Lower Silesian Voivodeship
53-203
Poland
Centrum Medyczne NeuroProtect
Warsaw
Masovian Voivodeship
01-684
Poland
Podlaskie Centrum Psychogeriatrii
Bialystok
Podlaskie Voivodeship
15-756
Poland
Centrum Badan Klinicznych PI-House sp. z o.o.
Gdansk
Pomeranian Voivodeship
80-546
Poland
Centrum Medyczne SENIOR
Sopot
Pomeranian Voivodeship
81-855
Poland
Centrum Medyczne Euromedis
Szczecin
West Pomeranian Voivodeship
70-111
Poland
FG001
3 mg LY3372689
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.
FG002
Placebo
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.
FG000110 subjects
FG001109 subjects
FG002108 subjects
Received at Least 1 Dose of Study Drug (Safety Population)
FG000108 subjects
FG001110 subjectsOne participant randomized to 0.75 mg LY3372689 moved to 3 mg LY3372689
FG002108 subjects
COMPLETED
FG00086 subjects
FG00170 subjects
FG00289 subjects
NOT COMPLETED
FG00024 subjects
FG00139 subjects
FG00219 subjects
Type
Comment
Reasons
Adverse Event
FG0001 subjects
FG0012 subjects
FG0021 subjects
Death
FG0000 subjects
FG0011 subjects
FG0021 subjects
Lost to Follow-up
FG0000 subjects
FG0011 subjects
FG0020 subjects
Physician Decision
FG0004 subjects
FG0013 subjects
FG0021 subjects
Progressive Disease
FG0000 subjects
FG0012 subjects
FG0020 subjects
Withdrawal by Subject
FG00017 subjects
FG00126 subjects
FG00214 subjects
Withdrawal Due To Caregiver Circumstances
FG0001 subjects
FG0011 subjects
FG0020 subjects
Participant randomized via Interactive Web Response System before Vital signs met Exclusion Criteria
FG0001 subjects
FG0010 subjects
FG0020 subjects
Participant no longer Wished to Continue with Investigational Product (IP) or Follow-up Visits
FG0000 subjects
FG0010 subjects
FG0021 subjects
Discontinued due to Common Close Design
FG0000 subjects
FG0011 subjects
FG0020 subjects
Participant not co-operative
FG0000 subjects
FG0011 subjects
FG0020 subjects
Participant Moving to Different Place from Where it takes 4 hours to Come to Site to Continue
FG0000 subjects
FG0010 subjects
FG0021 subjects
Caregiver Withdrew Consent due to Participant Moved to Long Term Care Home
FG0000 subjects
FG0011 subjects
FG0020 subjects
Post-Treatment Follow-Up Period
Type
Comment
Milestone Data
STARTED
Per the statistical analysis plan, safety data from the post-treatment follow-up period and the post-treatment observational extension period were pooled for adverse event analyses.
FG00083 subjectsExcludes participants who completed double-blind treatment and did not enter the post-treatment follow-up period.
FG00171 subjectsExcludes participants who completed double-blind treatment and did not enter the post-treatment follow-up period.
FG00288 subjectsExcludes participants who completed double-blind treatment and did not enter the post-treatment follow-up period.
COMPLETED
Male participants in the pooled Post-Treatment Follow-Up and Post-Treatment Observational Extension Period safety population: 0.75 mg LY3372689 = 30, 3 mg LY3372689 = 29, Placebo = 35. These counts are used as at-risk denominators for gender-specific adverse events.
FG00080 subjects
FG00164 subjects
FG00283 subjects
NOT COMPLETED
FG0003 subjects
FG0017 subjects
FG0025 subjects
Type
Comment
Reasons
Death
FG0001 subjects
FG0011 subjects
FG0021 subjects
Subject Moved Out of State
FG000
Post-Treatment Observational Extension
Type
Comment
Milestone Data
STARTED
Per the statistical analysis plan, safety data from the post-treatment follow-up period and the post-treatment observational extension period were pooled for adverse event analyses.
FG00042 subjectsExcludes participants who completed post-treatment follow-up period and did not enter the post-treatment observational extension period.
FG00138 subjectsExcludes participants who completed post-treatment follow-up period and did not enter the post-treatment observational extension period.
FG00242 subjectsExcludes participants who completed post-treatment follow-up period and did not enter the post-treatment observational extension period.
COMPLETED
FG00040 subjects
FG00132 subjects
FG00240 subjects
NOT COMPLETED
FG0002 subjects
FG0016 subjects
FG0022 subjects
Type
Comment
Reasons
Death
FG0000 subjects
FG0011 subjects
FG0020 subjects
Withdrawal by Subject
FG000
All randomized participants.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
0.75 mg LY3372689
Double-blind treatment period: Participants received 0.75 mg LY3372689 administered orally once daily for up to 124 weeks.
BG001
3 mg LY3372689
Double-blind treatment period: Participants received 3 mg LY3372689 administered orally once daily for up to 124 weeks.
BG002
Placebo
Double-blind treatment period: Participants received placebo administered orally once daily for up to 124 weeks.
Integrated Alzheimer's Disease Rating Scale is used to assess whether LY3372689 slows down the clinical decline associated with Alzheimer's disease (AD) compared with placebo. iADRS is an integrated assessment of cognition and daily function comprised of items from the Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog13) and the Alzheimer's disease cooperative study-instrumental activities of daily living scale (ADCS-iADL). The scale ranges from 0 to 144, where lower scores indicate worse performance and higher score indicates better performance
Mean
Standard Deviation
Score on a scale
Title
Denominators
Categories
Title
Measurements
BG000111.8± 11.99
BG001
Screening Tau Category
All randomized participants (pts) who have only evaluable Screening Tau category data. Intermediate tau (Low-medium): All pts with screening composite tau PET standardized uptake value ratio (SUVr) <= 1.46 and a topographic deposition pattern consistent with advanced AD (AD++) or 1.10 <= SUVr <= 1.46 and a topographic deposition pattern consistent with moderate AD (AD+).
High tau:All pts with SUVr >1.46 and topographic deposition pattern consistent with either moderate (AD+) or advanced AD (AD++).
Count of Participants
Participants
No
Title
Denominators
Categories
Intermediate (Low-medium)
Title
Measurements
BG00087
BG001
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
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.
All randomized participants with baseline or post-baseline data for this outcome with baseline Intermediate Tau level.
Posted
Mean
95% Confidence Interval
score on a scale
Baseline, Week 100
ID
Title
Description
OG000
0.75 mg LY3372689
Participants received 0.75 mg LY3372689 administered orally once daily for up to 124 weeks.
OG001
3 mg LY3372689
Participants received 3 mg LY3372689 administered orally once daily for up to 124 weeks.
OG002
Placebo
Participants received placebo administered orally once daily for up to 124 weeks.
Units
Counts
Participants
OG00086
OG00185
OG00284
Title
Denominators
Categories
Title
Measurements
OG000NA(NA to NA)The posterior mean = -8.39, 95% credible interval (-10.219 to -6.640)
OG001NA(NA to NA)The posterior mean = -13.27, 95% credible interval (-15.481 to -11.097)
OG002
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG002
Posterior Mean Difference
1.68
2-Sided
95
-0.375
3.771
Posterior mean difference with 95% credible interval is reported.
Superiority
OG001
OG002
Secondary
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.
All randomized participants with baseline or post-baseline data for this outcome.
Posted
Mean
95% Confidence Interval
score on a scale
Baseline, Week 100
ID
Title
Description
OG000
0.75 mg LY3372689
Participants received 0.75 mg LY3372689 administered orally once daily for up to 124 weeks.
OG001
3 mg LY3372689
Participants received 3 mg LY3372689 administered orally once daily for up to 124 weeks.
OG002
Placebo
Secondary
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.
All randomized participants with baseline or post-baseline data for this outcome with baseline Intermediate Tau level.
Posted
Least Squares Mean
Standard Error
score on a scale
Baseline, Week 76
ID
Title
Description
OG000
0.75mg LY3372689
Participants received 0.75 mg LY3372689 administered orally once daily for up to 124 weeks.
OG001
3 mg LY3372689
Participants received 3 mg LY3372689 administered orally once daily for up to 124 weeks.
OG002
Secondary
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.
All randomized participants with baseline or post-baseline data for this outcome.
Posted
Least Squares Mean
Standard Error
score on a scale
Baseline, Week 76
ID
Title
Description
OG000
0.75mg LY3372689
Participants received 0.75 mg LY3372689 administered orally once daily for up to 124 weeks.
OG001
3 mg LY3372689
Participants received 3 mg LY3372689 administered orally once daily for up to 124 weeks.
OG002
Placebo
Secondary
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.
All randomized participants with baseline or post-baseline data for this outcome with baseline Intermediate Tau level.
Posted
Least Squares Mean
Standard Error
score on a scale
Baseline, Week 76
ID
Title
Description
OG000
0.75mg LY3372689
Participants received 0.75 mg LY3372689 administered orally once daily for up to 124 weeks.
OG001
3 mg LY3372689
Participants received 3 mg LY3372689 administered orally once daily for up to 124 weeks.
Secondary
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.
All randomized participants with baseline or post-baseline data for this outcome.
Posted
Least Squares Mean
Standard Error
score on a scale
Baseline, Week 76
ID
Title
Description
OG000
0.75mg LY3372689
Participants received 0.75 mg LY3372689 administered orally once daily for up to 124 weeks.
OG001
3 mg LY3372689
Participants received 3 mg LY3372689 administered orally once daily for up to 124 weeks.
Secondary
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.
All randomized participants with baseline or post-baseline data for this outcome with baseline Intermediate Tau level.
Posted
Least Squares Mean
Standard Error
score on a scale
Baseline, Week 76
ID
Title
Description
OG000
0.75mg LY3372689
Participants received 0.75 mg LY3372689 administered orally once daily for up to 124 weeks.
OG001
3 mg LY3372689
Participants received 3 mg LY3372689 administered orally once daily for up to 124 weeks.
OG002
Secondary
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.
All randomized participants with baseline or post-baseline data for this outcome.
Posted
Least Squares Mean
Standard Error
score on a scale
Baseline, Week 76
ID
Title
Description
OG000
0.75mg LY3372689
Participants received 0.75 mg LY3372689 administered orally once daily for up to 124 weeks.
OG001
3 mg LY3372689
Participants received 3 mg LY3372689 administered orally once daily for up to 124 weeks.
OG002
Placebo
Secondary
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.
All randomized participants with baseline or post-baseline data for this outcome with baseline Intermediate Tau level.
Posted
Least Squares Mean
Standard Error
score on a scale
Baseline, Week 76
ID
Title
Description
OG000
0.75mg LY3372689
Participants received 0.75 mg LY3372689 administered orally once daily for up to 124 weeks.
OG001
3 mg LY3372689
Participants received 3 mg LY3372689 administered orally once daily for up to 124 weeks.
OG002
Placebo
Participants received placebo administered orally once daily for up to 124 weeks.
Secondary
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.
All randomized participants with baseline or post-baseline data for this outcome.
Posted
Least Squares Mean
Standard Error
score on a scale
Baseline, Week 76
ID
Title
Description
OG000
0.75mg LY3372689
Participants received 0.75 mg LY3372689 administered orally once daily for up to 124 weeks.
OG001
3 mg LY3372689
Participants received 3 mg LY3372689 administered orally once daily for up to 124 weeks.
OG002
Placebo
Participants received placebo administered orally once daily for up to 124 weeks.
Secondary
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).
All randomized participants with baseline Intermediate Tau level and with baseline and at least one postbaseline PET tau data.
Posted
Least Squares Mean
Standard Error
standardized uptake value ratio (SUVR)
Baseline, Week 76
ID
Title
Description
OG000
0.75mg LY3372689
Participants received 0.75 mg LY3372689 administered orally once daily for up to 124 weeks.
OG001
3 mg LY3372689
Participants received 3 mg LY3372689 administered orally once daily for up to 124 weeks.
Secondary
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).
All randomized participants with baseline and post-baseline PET tau data.
Posted
Least Squares Mean
Standard Error
SUVR
Baseline, Week 76
ID
Title
Description
OG000
0.75mg LY3372689
Participants received 0.75 mg LY3372689 administered orally once daily for up to 124 weeks.
OG001
3 mg LY3372689
Participants received 3 mg LY3372689 administered orally once daily for up to 124 weeks.
OG002
Placebo
Secondary
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.
All randomized participants with baseline Intermediate Tau level and with baseline and at least one postbaseline vMRI data.
Posted
Least Squares Mean
Standard Error
cubic centimeter (cm^3)
Baseline, Week 76
ID
Title
Description
OG000
0.75mg LY3372689
Participants received 0.75 mg LY3372689 administered orally once daily for up to 124 weeks.
OG001
3 mg LY3372689
Participants received 3 mg LY3372689 administered orally once daily for up to 124 weeks.
OG002
Placebo
Secondary
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.
All randomized participants with baseline and at least one postbaseline vMRI data.
Posted
Least Squares Mean
Standard Error
cm^3
Baseline, Week 76
ID
Title
Description
OG000
0.75mg LY3372689
Participants received 0.75 mg LY3372689 administered orally once daily for up to 124 weeks.
OG001
3 mg LY3372689
Participants received 3 mg LY3372689 administered orally once daily for up to 124 weeks.
OG002
Placebo
Participants received placebo administered orally once daily for up to 124 weeks.
Secondary
Pharmacokinetics (PK): Plasma Concentrations of LY3372689
Blood samples were measured at week 64 to assess the concentration of LY3372689 in the plasma.
All randomized participants who received at least one 1 of study drug and had evaluable C-trough data at the specified time points
Posted
Geometric Mean
Geometric Coefficient of Variation
nanograms per milliliter (ng/mL)
Week 64: Post-dose
ID
Title
Description
OG000
0.75 mg LY3372689
Participants received 0.75 mg LY3372689 administered orally once daily for up to 124 weeks.
OG001
3 mg LY3372689
Participants received 3 mg LY3372689 administered orally once daily for up to 124 weeks.
Units
Counts
Participants
OG000
Time Frame
Up to 124 weeks (Double-blind treatment period); 9 months on average (Post-treatment follow-up and Post treatment observational extension period)
Description
Safety population for double-blind treatment period includes all randomized participants (pts) who received at least one dose of study drug.
For post-treatment period,safety population includes all pts with safety data from post-treatment follow-up period and/or post-treatment observational extension period. Per statistical analysis plan,safety data from these two periods were pooled for adverse event analyses.Gender-specific events have had number of participants at risk adjusted accordingly.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
0.75 mg LY3372689 (Double Blind Period)
Participants received 0.75 mg LY3372689 administered orally once daily for up to 124 weeks during the double-blind treatment period.
0
108
13
108
75
108
EG001
3 mg LY3372689 (Double Blind Period)
Participants received 3 mg LY3372689 administered orally once daily for up to 124 weeks during the double-blind treatment period.
1
110
29
110
72
110
EG002
Placebo (Double Blind Period)
Participants received placebo administered orally once daily for up to 124 weeks during the double-blind treatment period.
1
108
16
108
81
108
EG003
0.75mg LY3372689 (Post-treatment Follow up Period and Post Treatment Observational Extension Period)
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.
1
83
2
83
0
83
EG004
3 mg LY3372689 (Post-treatment Follow up Period and Post Treatment Observational Extension Period)
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.
2
71
4
71
0
71
EG005
Placebo (Post-treatment Follow up Period and Post Treatment Observational Extension Period)
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.
1
88
9
88
0
88
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia macrocytic
Blood and lymphatic system disorders
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0011 events1 affected110 at risk
EG0020 events0 affected108 at risk
EG0030 events0 affected83 at risk
EG0040 events0 affected71 at risk
EG0050 events0 affected88 at risk
Angina unstable
Cardiac disorders
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0010 events0 affected110 at risk
EG0020 events0 affected108 at risk
EG003
Arteriosclerosis coronary artery
Cardiac disorders
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0010 events0 affected110 at risk
EG0020 events0 affected108 at risk
EG003
Atrial fibrillation
Cardiac disorders
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0013 events3 affected110 at risk
EG0021 events1 affected108 at risk
EG003
Atrioventricular block complete
Cardiac disorders
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0011 events1 affected110 at risk
EG0020 events0 affected108 at risk
EG003
Cardiac failure congestive
Cardiac disorders
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0010 events0 affected110 at risk
EG0020 events0 affected108 at risk
EG003
Left ventricular failure
Cardiac disorders
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0010 events0 affected110 at risk
EG0020 events0 affected108 at risk
EG003
Myocardial infarction
Cardiac disorders
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0010 events0 affected110 at risk
EG0020 events0 affected108 at risk
EG003
Palpitations
Cardiac disorders
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0011 events1 affected110 at risk
EG0020 events0 affected108 at risk
EG003
Stress cardiomyopathy
Cardiac disorders
MedDRA 28.0
Systematic Assessment
EG0001 events1 affected108 at risk
EG0010 events0 affected110 at risk
EG0020 events0 affected108 at risk
EG003
Tachycardia paroxysmal
Cardiac disorders
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0011 events1 affected110 at risk
EG0020 events0 affected108 at risk
EG003
Vertigo
Ear and labyrinth disorders
MedDRA 28.0
Systematic Assessment
EG0001 events1 affected108 at risk
EG0010 events0 affected110 at risk
EG0020 events0 affected108 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0011 events1 affected110 at risk
EG0020 events0 affected108 at risk
EG003
Diverticulum intestinal haemorrhagic
Gastrointestinal disorders
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0011 events1 affected110 at risk
EG0020 events0 affected108 at risk
EG003
Gastric ulcer
Gastrointestinal disorders
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0011 events1 affected110 at risk
EG0020 events0 affected108 at risk
EG003
Inguinal hernia
Gastrointestinal disorders
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0010 events0 affected110 at risk
EG0021 events1 affected108 at risk
EG003
Oesophageal ulcer
Gastrointestinal disorders
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0010 events0 affected110 at risk
EG0021 events1 affected108 at risk
EG003
Rectal haemorrhage
Gastrointestinal disorders
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0010 events0 affected110 at risk
EG0020 events0 affected108 at risk
EG003
Chest pain
General disorders
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0011 events1 affected110 at risk
EG0020 events0 affected108 at risk
EG003
Death
General disorders
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0010 events0 affected110 at risk
EG0020 events0 affected108 at risk
EG003
Non-cardiac chest pain
General disorders
MedDRA 28.0
Systematic Assessment
EG0001 events1 affected108 at risk
EG0011 events1 affected110 at risk
EG0020 events0 affected108 at risk
EG003
Bile duct stone
Hepatobiliary disorders
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0010 events0 affected110 at risk
EG0020 events0 affected108 at risk
EG003
Appendicitis
Infections and infestations
MedDRA 28.0
Systematic Assessment
EG0001 events1 affected108 at risk
EG0010 events0 affected110 at risk
EG0020 events0 affected108 at risk
EG003
Atypical pneumonia
Infections and infestations
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0010 events0 affected110 at risk
EG0020 events0 affected108 at risk
EG003
Cellulitis
Infections and infestations
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0010 events0 affected110 at risk
EG0021 events1 affected108 at risk
EG003
Covid-19
Infections and infestations
MedDRA 28.0
Systematic Assessment
EG0001 events1 affected108 at risk
EG0011 events1 affected110 at risk
EG0020 events0 affected108 at risk
EG003
Covid-19 pneumonia
Infections and infestations
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0011 events1 affected110 at risk
EG0020 events0 affected108 at risk
EG003
Dental sepsis
Infections and infestations
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0011 events1 affected110 at risk
EG0020 events0 affected108 at risk
EG003
Encephalitis
Infections and infestations
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0010 events0 affected110 at risk
EG0021 events1 affected108 at risk
EG003
Gastrointestinal fungal infection
Infections and infestations
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0011 events1 affected110 at risk
EG0020 events0 affected108 at risk
EG003
Perirectal abscess
Infections and infestations
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0011 events1 affected110 at risk
EG0020 events0 affected108 at risk
EG003
Pneumonia
Infections and infestations
MedDRA 28.0
Systematic Assessment
EG0001 events1 affected108 at risk
EG0011 events1 affected110 at risk
EG0022 events2 affected108 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0011 events1 affected110 at risk
EG0021 events1 affected108 at risk
EG003
Urosepsis
Infections and infestations
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0011 events1 affected110 at risk
EG0020 events0 affected108 at risk
EG003
Compression fracture
Injury, poisoning and procedural complications
MedDRA 28.0
Systematic Assessment
EG0001 events1 affected108 at risk
EG0010 events0 affected110 at risk
EG0020 events0 affected108 at risk
EG003
Concussion
Injury, poisoning and procedural complications
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0010 events0 affected110 at risk
EG0021 events1 affected108 at risk
EG003
Craniocerebral injury
Injury, poisoning and procedural complications
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0011 events1 affected110 at risk
EG0020 events0 affected108 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0012 events2 affected110 at risk
EG0021 events1 affected108 at risk
EG003
Femur fracture
Injury, poisoning and procedural complications
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0011 events1 affected110 at risk
EG0020 events0 affected108 at risk
EG003
Infusion related reaction
Injury, poisoning and procedural complications
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0010 events0 affected110 at risk
EG0020 events0 affected108 at risk
EG003
Lower limb fracture
Injury, poisoning and procedural complications
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0010 events0 affected110 at risk
EG0021 events1 affected108 at risk
EG003
Pelvic fracture
Injury, poisoning and procedural complications
MedDRA 28.0
Systematic Assessment
EG0001 events1 affected108 at risk
EG0010 events0 affected110 at risk
EG0020 events0 affected108 at risk
EG003
Postoperative delirium
Injury, poisoning and procedural complications
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0011 events1 affected110 at risk
EG0020 events0 affected108 at risk
EG003
Rib fracture
Injury, poisoning and procedural complications
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0010 events0 affected110 at risk
EG0021 events1 affected108 at risk
EG003
Spinal column injury
Injury, poisoning and procedural complications
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0011 events1 affected110 at risk
EG0020 events0 affected108 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0010 events0 affected110 at risk
EG0020 events0 affected108 at risk
EG003
Diabetic ketoacidosis
Metabolism and nutrition disorders
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0011 events1 affected110 at risk
EG0020 events0 affected108 at risk
EG003
Failure to thrive
Metabolism and nutrition disorders
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0010 events0 affected110 at risk
EG0020 events0 affected108 at risk
EG003
Hyponatraemia
Metabolism and nutrition disorders
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0011 events1 affected110 at risk
EG0020 events0 affected108 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0010 events0 affected110 at risk
EG0020 events0 affected108 at risk
EG003
Osteoarthritis
Musculoskeletal and connective tissue disorders
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0010 events0 affected110 at risk
EG0021 events1 affected108 at risk
EG003
Spinal osteoarthritis
Musculoskeletal and connective tissue disorders
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0010 events0 affected110 at risk
EG0021 events1 affected108 at risk
EG003
Adenocarcinoma of colon
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0011 events1 affected110 at risk
EG0020 events0 affected108 at risk
EG003
Diffuse large b-cell lymphoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0010 events0 affected110 at risk
EG0021 events1 affected108 at risk
EG003
Follicular lymphoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 28.0
Systematic Assessment
EG0001 events1 affected108 at risk
EG0010 events0 affected110 at risk
EG0020 events0 affected108 at risk
EG003
Haematological malignancy
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 28.0
Systematic Assessment
EG0000 events0 affected108 at risk
EG0011 events1 affected110 at risk
EG0020 events0 affected108 at risk
EG003
Lung adenocarcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 28.0
Systematic Assessment
EG0001 events1 affected108 at risk
EG0010 events0 affected110 at risk
EG0020 events0 affected108 at risk
EG003
Prostate cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)