A Study of LY3202626 on Disease Progression in Participants With Mild Alzheimer's Disease Dementia

Alzheimer's Disease Clinical Trial

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Official title:

Effect of LY3202626 on Alzheimer's Disease Progression as Measured by Cerebral ¹⁸F-AV-1451 Tau-PET in Mild Alzheimer's Disease Dementia

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02791191
• Other study ID #: 16223
• Secondary ID: I7X-MC-LLCF
• Status: Terminated
• Phase: Phase 2
• Start date: June 16, 2016
• Est. completion date: July 2, 2018

Study information

• Verified date: March 2021
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main purpose of this study is to evaluate the safety and the effect on brain tau of the study drug LY3202626 in participants with mild Alzheimer's disease (AD) dementia.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 316
• Est. completion date: July 2, 2018
• Est. primary completion date: July 2, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years to 85 Years

Eligibility

Inclusion Criteria:

• Present with mild AD dementia based on the National Institute on Aging (NIA) and the Alzheimer's Association (AA) disease diagnostic criteria as determined by a qualified clinician approved by the Sponsor or designee.

• Mini-Mental State Examination score of 20 to 26 inclusive at screening visit.

• Has a florbetapir PET scan consistent with the presence of amyloid pathology at screening.

Exclusion Criteria:

• Significant neurological disease affecting the central nervous system (CNS), other than AD, that may affect cognition or ability to complete the study, including but not limited to, other dementias, serious infection of the brain, Parkinson's disease, multiple concussions, or epilepsy or recurrent seizures (except febrile childhood seizures).

• Ocular pathology that significantly limits ability to reliably evaluate vision or the retina.

• Use of strong inducers of cytochrome P450 3A (CYP3A).

• Sensitivity to florbetapir or ¹8F-AV-1451.

• Contraindication to MRI or PET or poor venous access for blood draws.

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease
• Dementia
• Disease Progression

Intervention

Drug:
• LY3202626
Administered orally
• Placebo
Administered orally

Locations

Country	Name	City	State
Australia	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Box Hill
Australia	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Chermside
Australia	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Darlinghurst
Australia	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Erina
Australia	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Glen Iris
Australia	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Heidelberg
Australia	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Herston
Australia	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Nedlands
Australia	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Parkville
Australia	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	West Perth
Canada	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Gatineau
Canada	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Ottawa
Canada	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Verdun
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Akashi
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Hachioji
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Ikeda
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Kasukabe-shi
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Kyoto
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Nagoya
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Nerima-ku
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Osaka
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Osaka
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Setagaya-ku
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Takamatsu
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Tokyo
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Wako
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Yokosuka-shi
United States	Abington Neurological Associates	Abington	Pennsylvania
United States	Albany Medical College	Albany	New York
United States	Lehigh Center for Clinical Research	Allentown	Pennsylvania
United States	Dent Neurological Institute	Amherst	New York
United States	Johns Hopkins University School of Medicine	Baltimore	Maryland
United States	Missouri Memory Center	Bolivar	Missouri
United States	Valley Medical Primary Care	Centerville	Ohio
United States	Clinical Trials of South Carolina	Charleston	South Carolina
United States	Clinical Research Professionals	Chesterfield	Missouri
United States	Millenium Psychiatric Associates LLC	Creve Coeur	Missouri
United States	Baylor AT&T Memory Center	Dallas	Texas
United States	Neurology Diagnostics, Inc.	Dayton	Ohio
United States	University of Cincinnati Health Neurology	Dayton	Ohio
United States	Memory Enhancement Center of America, Inc.	Eatontown	New Jersey
United States	Fort Wayne Neurological Center	Fort Wayne	Indiana
United States	United Osteoporosis Center	Gainesville	Georgia
United States	Nantz National Alzheimer Center	Houston	Texas
United States	University of Texas Health Services Center - Houston	Houston	Texas
United States	Indiana University School of Medicine	Indianapolis	Indiana
United States	Irvine Clinical Research Center	Irvine	California
United States	Clinical Neuroscience Solutions Inc	Jacksonville	Florida
United States	Clinical Trial Center, LLC, Psychiatry	Jenkintown	Pennsylvania
United States	St Lukes Hospital	Kansas City	Missouri
United States	Las Vegas Medical Research	Las Vegas	Nevada
United States	Compass Research	Melbourne	Florida
United States	Florida International Research Center	Miami	Florida
United States	New Horizon Research Center	Miami	Florida
United States	The Neurology Research Group, LLC	Miami	Florida
United States	Pyramid Clinical Research	Monroe	New Jersey
United States	Suncoast Clinical Research	New Port Richey	Florida
United States	Boston Center for Memory	Newton	Massachusetts
United States	Renstar Medical Research	Ocala	Florida
United States	Sensible Healthcare	Ocoee	Florida
United States	Sutter Medical Group	Sacramento	California
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Pacific Research Network Inc	San Diego	California
United States	Sharp Mesa Vista Hospital	San Diego	California
United States	Ray Dolby Brain Health Center/Sutter Health/CPMC	San Francisco	California
United States	Syrentis Clinical Research	Santa Ana	California
United States	North Bay Neuroscience Institute	Sebastopol	California
United States	Insight Clinical Trials	Shaker Heights	Ohio
United States	Meridien Research	Spring Hill	Florida
United States	New England Institute for Clinical Research	Stamford	Connecticut
United States	Axiom Research	Tampa	Florida
United States	Advanced Memory Research Institute of New Jersey	Toms River	New Jersey
United States	Bio Behavioral Health	Toms River	New Jersey
United States	Cotton O'Neil Clinic	Topeka	Kansas
United States	Heartland Research Associates	Wichita	Kansas
United States	Christiana Care Health Service	Wilmington	Delaware

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in ¹8F-AV-1451 Positron Emission Tomography (PET) Standard Uptake Value Ratio (SUVr) at 52 Weeks	The 18F-AV-1451 PET tracer assesses change from baseline in the pharmacodynamic effect of 3 mg and 12 mg doses of LY3202626 in participants with mild Alzheimer's disease (AD), compared with placebo at Week 52.The SUVr of ¹8F-AV-1451 was modeled using analysis of covariance (ANCOVA) to include the fixed, categorical effects of treatment dose, and the continuous, fixed covariate of baseline Tau PET SUVr and age at baseline.	Baseline, Week 52
Secondary	Percentage of Participants With Emergent Magnetic Resonance Imaging (MRI) Findings	Percentage of participants with treatment-emergent MRI findings at Week 52 are summarized here. The mixed-effect model for repeated measures (MMRM) analysis was adjusted for fixed effects of treatment, visit (categorical covariate), treatment-by-visit interaction, baseline age, baseline score (continuous covariate) and baseline-by-visit interaction.	Week 52
Secondary	Percentage of Participants With Amyloid-Related Imaging Abnormalities (ARIA)	Percentage of participants with presence of amyloid-related imaging abnormalities-edema (ARIA-E, also known as vasogenic edema) and percentage of an increase in amyloid-related imaging abnormalities-hemorrhage (ARIA-H, also known as also known as microhemorrhage) at Week 52 are summarized here. The mixed-effect model for repeated measures (MMRM) analysis was adjusted for fixed effects of treatment, visit (categorical covariate), treatment-by-visit interaction, baseline age, baseline score (continuous covariate) and baseline-by-visit interaction.	Week 52
Secondary	Percentage of Participants With Suicidal Ideation and Behaviors Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) Scores	The Columbia-Suicide Severity Rating Scale (C-SSRS) captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal ideation is defined as a "yes" answer to any 1 of 5 suicidal ideation questions, which includes a wish to be dead and 4 different categories of active suicidal ideation. Suicidal behavior is defined as a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation and behavior are defined as treatment-emergent (TE) if not present during the period up through randomization. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Event module.	Baseline through Week 52
Secondary	Pharmacokinetics (PK): Area Under the Plasma Concentration-Time Curve at Steady State (AUC [T,SS]) of LY3202626	PK: AUC [T,SS] of LY3202626	Week 2, 4, and 12: Predose and Postdose prior to departing; Week 8 and 16: Postdose after arriving and prior to departing; Week 24: Postdose after cognitive testing
Secondary	Change From Baseline in Plasma Amyloid Beta Aß1-40, 1-42, and 1-x Concentration	A mixed model repeated measures (MMRM) analysis will be used to evaluate the change from baseline to Week 52 in plasma Aß1-40, Aß1-42, and Aß 1-x. The model for the fixed effects will include terms for the following independent effects: log transformed baseline plasma Aß, treatment, visit, treatment-by-visit interaction.	Baseline, Week 52
Secondary	Change From Baseline on the 13-item Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog13)	The ADAS is a rater administered instrument that was designed to assess the severity of the dysfunction in the cognitive and noncognitive behaviors characteristic of persons with AD. The cognitive subscale of the ADAS that was used as the primary efficacy measure 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. A mixed model repeated measures (MMRM) was used in analysis. The model included fixed, categorical effects of treatment, visit and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline, baseline-by-visit, and age at baseline.	Baseline, Week 52
Secondary	Change From Baseline on the Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living Inventory (ADCS-iADL)	The ADCS-ADL is a 23-item inventory developed as a rater-administered questionnaire answered by the participant's caregiver. The ADCS-ADL measures both basic and instrumental activities (instrumental activity items 7-23) of daily living by participants. The range for the ADCS-iADL is 0-56 with higher scores reflecting better performance. ADCS-iADL was analyzed using mixed-model repeated measures (MMRM), Least Square (LS) Mean was controlled for treatment, visit, treatment-by-visit interaction, baseline age, baseline score and baseline-by-visit interaction.	Baseline, Week 52
Secondary	Change From Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS)	The iADRS comprises scores form the ADAS-Cog and the ADCS-iADL. The iADRS is calculated as a linear combination of the total scores of the ADAS-Cog13 9score range 0 to 85 with higher scores reflecting worse performance and the ADCS-iADL (score range 0-56 with higher scores reflecting better performance). The iADRS score ranges from 0 to 141 with lower scores indicating worse performance. iADRS was analyzed using mixed-model repeated measures (MMRM); Least Square (LS) Mean was controlled for treatment, visit, treatment-by-visit interaction, baseline age, baseline score and baseline-by-visit interaction.	Baseline, Week 52

External Links

•   Click here for more information about this study: A Study of LY3202626 on Disease Progression in Participants With Mild Alzheimer's Disease Dementia (NAVIGATE-AD)