A Study of LY3303560 in Participants With Early Symptomatic Alzheimer's Disease

Assessment of Safety, Tolerability, and Efficacy of LY3303560 in Early Symptomatic Alzheimer's Disease

The purpose of this study is to evaluate the safety and efficacy of a study drug that targets an abnormal protein in the brain found in people with Alzheimer's Disease (AD).

Study Overview

• Status: Completed
• Conditions: Alzheimer Disease (AD)
• Intervention / Treatment: Drug: Placebo; Drug: Zagotenemab

• Study Type: Interventional
• Enrollment (Actual): 360
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ca-on
    • Peterborough, Ca-on, Canada, K9H 2P4
      • Kawartha Centre - Redefining Healthy Aging
  • Ontario
    • Toronto, Ontario, Canada, M3B2S7
      • Toronto Memory Program
  • Quebec
    • Gatineau, Quebec, Canada, J8T 8J1
      • Clinique de la Memoire de l'Outaouais
    • Greenfield Park, Quebec, Canada, J4V 2J2
      • NeuroSearch Developements
    • Sherbrooke, Quebec, Canada, J1J 2G2
      • Q&T Research Sherbrooke Inc.
• Japan
  • Aichi
    • Obu City, Aichi, Japan, 4748511
      • National Center for Geriatrics and Gerontology
  • Hyogo
    • Kobe, Hyogo, Japan, 650-0046
      • Kobe City Medical Center General Hospital
  • Jp-13
    • Tokyo, Jp-13, Japan, 113-8603
      • Nippon Medical School Hospital
  • Jp-26
    • Kyoto, Jp-26, Japan, 616-8255
      • National Hospital Organization Utano National Hospital
  • Jp-33
    • Kurashiki, Jp-33, Japan, 710-0813
      • Katayama Medical Clinic
  • Kanagawa
    • Kamakura, Kanagawa, Japan, 247-8533
      • Shonan Kamakura General Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Banner Alzheimer's Institute
    • Tucson, Arizona, United States, 85718
      • Center For Neurosciences
  • California
    • Encino, California, United States, 91316
      • Pharmacology Research Institute
    • Fullerton, California, United States, 92835
      • Fullerton Neurology and Headache Center
    • Irvine, California, United States, 92614
      • Irvine Clinical Research Center
    • Los Alamitos, California, United States, 90720
      • Pharmacology Research Institute
    • Panorama City, California, United States, 91402
      • National Research Institute - Huntington Park
    • Redlands, California, United States, 92374
      • Anderson Clinical Research
    • San Diego, California, United States, 92103
      • Pacific Research Network
    • San Francisco, California, United States, 94158
      • Univ of California San Francisco
    • Santa Ana, California, United States, 92705
      • Syrentis Clinical Research
  • Connecticut
    • Stamford, Connecticut, United States, 06905
      • New England Institute for Clinical Research
  • Florida
    • Atlantis, Florida, United States, 33462
      • JEM Research Institute
    • Aventura, Florida, United States, 33180
      • Julie B. Schwartzbard, MD, PA
    • Deerfield Beach, Florida, United States, 33064
      • Quantum Laboratories Clinical Research
    • Delray Beach, Florida, United States, 33445
      • Brain Matters Research
    • Fort Myers, Florida, United States, 33912
      • Neuropsychiatric Research Center of Southwest Florida
    • Hollywood, Florida, United States, 33024
      • Infinity Clinical Research, LLC
    • Miami, Florida, United States, 33176
      • VIN-Victor Faradji
    • Ocala, Florida, United States, 34470
      • Renstar Medical Research
    • Orlando, Florida, United States, 32806
      • BioClinica Inc
    • Port Orange, Florida, United States, 32127
      • Progressive Medical Research
    • Stuart, Florida, United States, 34997
      • Brain Matters Research
    • Sunrise, Florida, United States, 33351
      • Infinity Clinical Research, LLC
  • Georgia
    • Columbus, Georgia, United States, 31909
      • Columbus Memory Center, PC
  • Illinois
    • Chicago, Illinois, United States, 60640
      • Great Lakes Clinical Trials
    • Elk Grove Village, Illinois, United States, 60007
      • AMITA Health - Alexian Brothers Neurosciences Institute Clinical Research
  • Indiana
    • Indianapolis, Indiana, United States, 46256
      • Josephson Wallack Munshower Neurology, PC
  • Kansas
    • Lenexa, Kansas, United States, 66214
      • Rowe Neurology Institute
    • Topeka, Kansas, United States, 66606
      • Cotton O'Neil Clinic
  • Maryland
    • Baltimore, Maryland, United States, 21208
      • Pharmasite Research, Inc.
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
    • Newton, Massachusetts, United States, 02459
      • Boston Center for Memory
  • Missouri
    • Chesterfield, Missouri, United States, 63005
      • Clinical Research Professionals
  • New Jersey
    • Springfield, New Jersey, United States, 07081
      • The Cognitive and Research Center of New Jersey
    • Toms River, New Jersey, United States, 08755
      • Advanced Memory Research Institute of New Jersey
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • Raleigh Neurology Associates, P.A.
    • Winston-Salem, North Carolina, United States, 27103
      • PMG Research of Winston-Salem, LLC
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Lindner Research Center
    • Columbus, Ohio, United States, 43210
      • Ohio State University Medical Center
    • Dayton, Ohio, United States, 45417
      • University of Cincinnati Health Neurology
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18104
      • Lehigh Center for Clinical Research
    • Media, Pennsylvania, United States, 19063
      • Suburban Research Associates
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • Butler Hospital
  • Texas
    • Dallas, Texas, United States, 75231
      • Baylor AT&T Memory Center
    • Dallas, Texas, United States, 75243
      • Neurology Consultants of Dallas, PA
    • Houston, Texas, United States, 77030
      • Houston Methodist Research Ins
  • Vermont
    • Bennington, Vermont, United States, 05201
      • The Memory Clinic
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Cognition Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participants must have gradual and progressive change in memory function for >6 months.
• Participants must have a family member or close friend who is with you at least 10 hours per week and can attend study appointments.

Exclusion Criteria:

• Participants must not have significant neurological disease affecting the nervous system, other than AD, that affects cognition or may affect completion of the study.
• Participants must not have serious or unstable illness that could interfere with the analysis of the study or has a life expectancy <24 months.
• Participants must not have history of cancer within the last 5 years with the exception of certain types of skin, cervical, prostate, and other cancers that are not likely to recur or spread.
• Participants must not have serious risk for suicide.
• Participants must not have history of drug or alcohol use disorder within the last 2 years.
• Participants must not have multiple severe drug allergies
• Participants must not have HIV, Hepatitis B or Hepatitis C
• Participants must not be receiving gamma globulin (IgG) or intravenous immunoglobulin (IVIG) therapy

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
Placebo Comparator: Placebo; Participants received intravenous (IV) infusion of placebo once every four weeks (Q4W) for 100 weeks.	Drug: Placebo; Administered IV
Experimental: Zagotenemab 1400 mg; Participants received IV infusion of 1400 milligram (mg) zagotenemab Q4W for 100 weeks.	Drug: Zagotenemab; Administered IV; Other Names: LY3303560
Experimental: Zagotenemab 5600 mg; Participants received IV infusion of 5600 mg zagotenemab Q4W for 100 weeks.	Drug: Zagotenemab; Administered IV; Other Names: LY3303560

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS)	Integrated Alzheimer's Disease Rating Scale (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 zagotenemab 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) with fixed, categorical effects of treatment, pooled site, acetylcholinesterase inhibitor (AChEI) use at baseline (yes/no), and the continuous effects of baseline score and age at baseline. Data presented are posterior mean with 95% credible interval.	Baseline, Week 104

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline on the Alzheimer's Disease Assessment Scale- Cognitive Subscale (ADAS-Cog13) Score	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 Alzheimer's Disease (AD). The cognitive subscale of the ADAS consists of 13 items assessing areas of cognitive function most typically impaired in AD: orientation, verbal memory, language, praxis, delayed free recall, digit cancellation, and maze completion measures. The ADAS-Cog13 scale ranges from 0 to 85, with higher scores indicating greater disease severity. Change from baseline was calculated using Bayesian disease progression model (DPM) with fixed, categorical effects of treatment, pooled site, acetylcholinesterase inhibitor (AChEI) use at baseline (yes/no), and the continuous effects of baseline score and age at baseline. Data presented are posterior mean with 95% credible interval.	Baseline, Week 104
Change From Baseline on the Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living Scale (ADCS-iADL) Score	The ADCS-ADL is a 23-item inventory developed as a rater-administered questionnaire answered by the participant's caregiver. The ADCS-ADL measures basic, instrumental activities of daily living by participants (instrumental activity items 6a, 7-23). The range for the ADCS-iADL is 0-59, with lower scores indicating greater disease severity. Change from baseline was calculated using Bayesian disease progression model (DPM) with fixed, categorical effects of treatment, pooled site, acetylcholinesterase inhibitor (AChEI) use at baseline (yes/no), and the continuous effects of baseline score and age at baseline. Data presented are posterior mean with 95% credible interval.	Baseline, Week 104
Change From Baseline on the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) Score	CDR-SB is a semi-structured interview of participants and their caregivers. Participant's cognitive status is rated across 6 domains of functioning: 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. Change from baseline was calculated using Bayesian disease progression model (DPM) with fixed, categorical effects of treatment, pooled site, acetylcholinesterase inhibitor (AChEI) use at baseline (yes/no), and the continuous effects of baseline score and age at baseline. Data presented are posterior mean with 95% credible interval.	Baseline, Week 104
Change From Baseline on the Mini Mental Status Examination (MMSE) Score	The MMSE is a brief instrument used to assess cognitive function. The instrument is divided into 2 sections. The first section measures orientation, memory, and attention. The maximum score for the first section is 21. The second section tests the ability of the person to name objects, follow verbal and written commands, write a sentence, and copy figures. The maximum score for the second section is 9. The range for the total MMSE score is 0 to 30, with lower scores indicating greater level of impairment. Change from baseline was calculated using Bayesian disease progression model (DPM) with fixed, categorical effects of treatment, pooled site, acetylcholinesterase inhibitor (AChEI) use at baseline (yes/no), and the continuous effects of baseline score and age at baseline. Data presented are posterior mean with 95% credible interval.	Baseline, Week 104
Change From Baseline in Brain Aggregated Tau Deposition as Measured by Flortaucipir F-18 Positron Emission Tomography (PET) Scan.	Deposition of abnormal tau protein in the brain associated with AD was assessed by quantitative PET scan using flortaucipir F-18. Flortaucipir is an F-18-labeled small molecule that binds with high affinity and selectivity to aggregated tau, and provides a measure of aggregated tau deposition in the brain, expressed as flortaucipir standardized uptake value ratio (SUVr). Change from baseline was calculated using mixed model repeated measures (MMRM) with fixed, categorical effects of treatment, visit, treatment-by-visit interaction, and continuous effect of baseline SUVr and age. A positive change from baseline indicates increased aggregated tau deposition that is believed to be associated with a more rapid rate of cognitive deterioration.	Baseline, Week 104
Change From Baseline in Brain Volume as Measured by Volumetric Magnetic Resonance Imaging (vMRI)	Alzheimer's disease is also associated with pronounced brain atrophy, reflecting bulk neurodegenerative loss of gray and white matter. Progression of brain atrophy is assessed by vMRI, providing regional quantification of volume loss. Negative change from baseline indicates greater disease severity. Change from baseline was calculated using mixed model repeated measures (MMRM) with fixed, categorical effects of treatment, visit, treatment-by-visit interaction, and continuous effect of baseline vMRI, baseline intracranial volume (ICV) and age.	Baseline, Week 104
Number of Participants With Suicidal Ideation and Behaviors Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS)	C-SSRS is a scale capturing occurrence, severity, and frequency of suicide-related thoughts and behaviours, and has a binary response (yes/no).; Suicidal Ideation: a "yes" answer to any one of 5 suicidal ideation questions: Wish to be Dead, Non-specific Active Suicidal Thoughts, Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act, Active Suicidal Ideation with Some Intent to Act without Specific Plan, Active Suicidal Ideation with Specific Plan and Intent.; Suicidal Behaviour: a "yes" answer to any of 5 suicidal behaviour questions: Preparatory Acts or Behaviour, Aborted Attempt, Interrupted Attempt, Actual Attempt (non-fatal), Completed Suicide.	Baseline through Week 104
Number of Participants With Treatment Emergent Anti-Drug Antibodies (TE-ADA) to Zagotenemab	A TE-ADA evaluable subject is considered to be TE-ADA positive: If the subject has at least one post baseline titer that is a 4-fold or greater increase in titer from baseline measurement (treatment-boosted).; If baseline result is ADA Not Present, then the subject is TE ADA positive if there is at least one postbaseline result of ADA Present with titer >= 1:10 (treatment-induced).	Baseline through Week 113

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

Helpful Links

• A Study of LY3303560 in Participants With Early Symptomatic Alzheimer's Disease

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2018
• Primary Completion (Actual): August 23, 2021
• Study Completion (Actual): October 25, 2021

Study Registration Dates

• First Submitted: April 26, 2018
• First Submitted That Met QC Criteria: May 1, 2018
• First Posted (Actual): May 8, 2018

Study Record Updates

• Last Update Posted (Actual): August 30, 2022
• Last Update Submitted That Met QC Criteria: August 12, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Dementia; Cognitive impairment; Tauopathy; Memory problems; Neurofibrillary tangles; PERISCOPE-ALZ
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: 16124; I8G-MC-LMDC (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD Plan Description

Lilly provides access to the individual patient data from studies on approved medicines and indications as defined by the sponsor specific information on ClinicalStudyDataRequest.com.

This access is provided in a timely fashion after the primary publication is accepted. Researchers need to have an approved research proposal submitted through ClinicalStudyDataRequest.com. Access to the data will be provided in a secure data sharing environment after signing a data sharing agreement.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No