A Study of LY3372689 to Assess the Safety, Tolerability, and Efficacy in Participants With Alzheimer's Disease
- Registration Number
- NCT05063539
- Lead Sponsor
- Eli Lilly and Company
- 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 available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 327
- 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
- Contraindication to MRI or PET scans
- Have known allergies to LY3372689, related compounds, or any components of the formulations
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 0.75 Milligram (mg) LY3372689 LY3372689 Participants received 0.75 mg LY3372689 administered orally once daily for up to 124 weeks 3 mg LY3372689 LY3372689 Participants received 3 mg LY3372689 administered orally once daily for up to 124 weeks. Placebo Placebo Participants received placebo administered orally once daily for up to 124 weeks.
- Primary Outcome Measures
Name Time Method Change From Baseline to End Time Point in Integrated Alzheimer's Disease Rating Scale (iADRS) (Intermediate (Low-medium) Tau Population) 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.
- Secondary Outcome Measures
Name Time Method Change From Baseline to End Time Point in iADRS (Overall Population) 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, baseline tau PET category, AChEI/Memantine use at baseline, pooled investigator. Data presented are posterior mean with 95% credible interval.
Change From Baseline to End Time Point in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) (Intermediate (Low-medium) Tau Population) Baseline, Week 76 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.
Change From Baseline to End Time Point in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) (Overall Population) Baseline, Week 76 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.
Change From Baseline to End Time Point in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) (Intermediate (Low-medium) Tau Population) Baseline, Week 76 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.
Change From Baseline to End Time Point in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) (Overall Population) Baseline, Week 76 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.
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) Baseline, Week 76 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.
Change From Baseline to End Time Point in Alzheimer's Disease Cooperative Study Instrumental Activities of Daily Living Inventory (ADCS-iADL) (Overall Population) Baseline, Week 76 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.
Change From Baseline to End Time Point in Mini Mental State Examination (MMSE) (Intermediate (Low-medium) Tau Population) Baseline, Week 76 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.
Change From Baseline to End Time Point in Mini Mental State Examination (MMSE) (Overall Population) Baseline, Week 76 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.
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) Baseline, Week 76 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).
Change From Baseline to End Time Point In Brain Tau Deposition as Measured by Flortaucipir F18 Positron Emission Tomography (PET) Scan (Overall Population) Baseline, Week 76 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).
Change From Baseline to End Time Point in Volumetric Magnetic Resonance Imaging (vMRI) Measures (Intermediate (Low-medium) Tau Population) Baseline, Week 76 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.
Change From Baseline to End Time Point in Volumetric Magnetic Resonance Imaging (vMRI) Measures (Overall Population) Baseline, Week 76 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.
Pharmacokinetics (PK): Plasma Concentrations of LY3372689 Week 64: Post-dose Blood samples were measured at week 64 to assess the concentration of LY3372689 in the plasma.
Trial Locations
- Locations (68)
St Vincent's Hospital
🇦🇺Sydney, New South Wales, Australia
Box Hill Hospital
🇦🇺Box Hill, Victoria, Australia
Hope Clinical Research, Inc.
🇺🇸Canoga Park, California, United States
Neuro-Pain Medical Center
🇺🇸Fresno, California, United States
Irvine Clinical Research
🇺🇸Irvine, California, United States
Sharp Mesa Vista Hospital
🇺🇸San Diego, California, United States
Institute for Neurodegenerative Disorders
🇺🇸New Haven, Connecticut, United States
JEM Research Institute
🇺🇸Atlantis, Florida, United States
VIN-Julie Schwartzbard
🇺🇸Aventura, Florida, United States
Neurology Offices of South Florida
🇺🇸Boca Raton, Florida, United States
Scroll for more (58 remaining)St Vincent's Hospital🇦🇺Sydney, New South Wales, Australia