A Study of LY3202626 on Disease Progression in Participants With Mild Alzheimer's Disease Dementia (NAVIGATE-AD)

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

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.

Study Overview

• Status: Terminated
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: Placebo; Drug: LY3202626

• Study Type: Interventional
• Enrollment (Actual): 316
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Box Hill, Australia, 3128
    • 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, 4032
    • 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, 2010
    • 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, 2250
    • 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, 3146
    • 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, 3084
    • 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, 4029
    • 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, 6009
    • 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, 3050
    • 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, Australia, 6005
    • 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.
• Canada
  • Gatineau, Canada, J8T 8J1
    • 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, KIN 5C8
    • 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, Canada, H4H 1R3
    • 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.
• Japan
  • Akashi, Japan, 673-0891
    • 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, 193-0998
    • 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, 563-0058
    • 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, 344-0036
    • 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, 606-0851
    • 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, 451-8511
    • 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, 179-0072
    • 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, 533-0004
    • 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, 559-0004
    • 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, 158-8531
    • 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, 760-8557
    • 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, 156-0041
    • 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, 351-0111
    • 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, Japan, 238-0042
    • 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.
• United States
  • California
    • Irvine, California, United States, 92614
      • Irvine Clinical Research Center
    • Sacramento, California, United States, 95816
      • Sutter Medical Group
    • San Diego, California, United States, 92123
      • Sharp Mesa Vista Hospital
    • San Diego, California, United States, 92103
      • Pacific Research Network Inc
    • San Francisco, California, United States, 94114
      • Ray Dolby Brain Health Center/Sutter Health/CPMC
    • Santa Ana, California, United States, 92705
      • Syrentis Clinical Research
    • Sebastopol, California, United States, 95472
      • North Bay Neuroscience Institute
  • Connecticut
    • Stamford, Connecticut, United States, 06905
      • New England Institute for Clinical Research
  • Delaware
    • Wilmington, Delaware, United States, 19801
      • Christiana Care Health Service
  • Florida
    • Jacksonville, Florida, United States, 32256
      • Clinical Neuroscience Solutions Inc
    • Melbourne, Florida, United States, 32940
      • Compass Research
    • Miami, Florida, United States, 33175
      • New Horizon Research Center
    • Miami, Florida, United States, 33173
      • Florida International Research Center
    • Miami, Florida, United States, 33176
      • The Neurology Research Group, LLC
    • New Port Richey, Florida, United States, 34652
      • Suncoast Clinical Research
    • Ocala, Florida, United States, 34470
      • Renstar Medical Research
    • Ocoee, Florida, United States, 34761
      • Sensible Healthcare
    • Spring Hill, Florida, United States, 34609
      • Meridien Research
    • Tampa, Florida, United States, 33609
      • Axiom Research
  • Georgia
    • Gainesville, Georgia, United States, 30501
      • United Osteoporosis Center
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Fort Wayne Neurological Center
    • Indianapolis, Indiana, United States, 46202
      • Indiana University School of Medicine
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Cotton O'Neil Clinic
    • Wichita, Kansas, United States, 67205
      • Heartland Research Associates
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins University School of Medicine
  • Massachusetts
    • Newton, Massachusetts, United States, 02459
      • Boston Center for Memory
  • Missouri
    • Bolivar, Missouri, United States, 65613
      • Missouri Memory Center
    • Chesterfield, Missouri, United States, 63005
      • Clinical Research Professionals
    • Creve Coeur, Missouri, United States, 63141
      • Millenium Psychiatric Associates LLC
    • Kansas City, Missouri, United States, 64111
      • St Lukes Hospital
    • Saint Louis, Missouri, United States, 63108
      • Washington University School of Medicine
  • Nevada
    • Las Vegas, Nevada, United States, 89113
      • Las Vegas Medical Research
  • New Jersey
    • Eatontown, New Jersey, United States, 07724
      • Memory Enhancement Center of America, Inc.
    • Monroe, New Jersey, United States, 08831
      • Pyramid Clinical Research
    • Toms River, New Jersey, United States, 08755
      • Advanced Memory Research Institute of New Jersey
    • Toms River, New Jersey, United States, 08755
      • Bio Behavioral Health
  • New York
    • Albany, New York, United States, 12206
      • Albany Medical College
    • Amherst, New York, United States, 14226
      • Dent Neurological Institute
  • Ohio
    • Centerville, Ohio, United States, 45459
      • Valley Medical Primary Care
    • Dayton, Ohio, United States, 45417
      • University of Cincinnati Health Neurology
    • Dayton, Ohio, United States, 45459
      • Neurology Diagnostics, Inc.
    • Shaker Heights, Ohio, United States, 44122
      • Insight Clinical Trials
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19090
      • Abington Neurological Associates
    • Allentown, Pennsylvania, United States, 18104
      • Lehigh Center for Clinical Research
    • Jenkintown, Pennsylvania, United States, 19046
      • Clinical Trial Center, LLC, Psychiatry
  • South Carolina
    • Charleston, South Carolina, United States, 29406
      • Clinical Trials of South Carolina
  • Texas
    • Dallas, Texas, United States, 75231
      • Baylor AT&T Memory Center
    • Houston, Texas, United States, 77030
      • Nantz National Alzheimer Center
    • Houston, Texas, United States, 77054
      • University of Texas Health Services Center - Houston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose 1 LY3202626; 3 mg LY3202626 given orally once daily for 52 weeks.	Drug: LY3202626; Administered orally
Experimental: Dose 2 LY3202626; 12 mg LY3202626 given orally once daily for 52 weeks.	Drug: LY3202626; Administered orally
Experimental: Placebo; Placebo given orally once daily for 52 weeks.	Drug: Placebo; Administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
Change From Baseline in Plasma Amyloid Beta Aβ₁-₄₀, 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 Aβ₁-₄₀, Aβ₁-₄₂, and Aβ 1-x. The model for the fixed effects will include terms for the following independent effects: log transformed baseline plasma Aβ, treatment, visit, treatment-by-visit interaction.	Baseline, Week 52
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
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
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

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

Helpful 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)

Study record dates

Study Major Dates

• Study Start (Actual): June 16, 2016
• Primary Completion (Actual): July 2, 2018
• Study Completion (Actual): July 2, 2018

Study Registration Dates

• First Submitted: June 1, 2016
• First Submitted That Met QC Criteria: June 1, 2016
• First Posted (Estimate): June 6, 2016

Study Record Updates

• Last Update Posted (Actual): April 19, 2021
• Last Update Submitted That Met QC Criteria: March 22, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: BACE inhibitor
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Disease Attributes; Neurodegenerative Diseases; Tauopathies; Disease Progression; Dementia; Alzheimer Disease
• Other Study ID Numbers: 16223; I7X-MC-LLCF (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: 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.
• IPD Sharing Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)