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

Alzheimer Disease (AD) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03518073
• Other study ID #: 16124
• Secondary ID: I8G-MC-LMDC
• Status: Completed
• Phase: Phase 2
• Start date: April 30, 2018
• Est. completion date: October 25, 2021

Study information

• Verified date: August 2022
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 360
• Est. completion date: October 25, 2021
• Est. primary completion date: August 23, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer Disease (AD)

Intervention

Drug:
• Zagotenemab
Administered IV
• Placebo
Administered IV

Locations

Country	Name	City	State
Canada	Clinique de la Mémoire de l'Outaouais	Gatineau	Quebec
Canada	NeuroSearch Developements	Greenfield Park	Quebec
Canada	Kawartha Centre - Redefining Healthy Aging	Peterborough	Ca-on
Canada	Q&T Research Sherbrooke Inc.	Sherbrooke	Quebec
Canada	Toronto Memory Program	Toronto	Ontario
Japan	Shonan Kamakura General Hospital	Kamakura	Kanagawa
Japan	Kobe City Medical Center General Hospital	Kobe	Hyogo
Japan	Katayama Medical Clinic	Kurashiki	Jp-33
Japan	National hospital Organization Utano National Hospital	Kyoto	Jp-26
Japan	National Center for Geriatrics and Gerontology	Obu City	Aichi
Japan	Nippon Medical School Hospital	Tokyo	Jp-13
United States	Lehigh Center for Clinical Research	Allentown	Pennsylvania
United States	JEM Research Institute	Atlantis	Florida
United States	Julie B. Schwartzbard, MD, PA	Aventura	Florida
United States	Pharmasite Research, Inc.	Baltimore	Maryland
United States	The Memory Clinic	Bennington	Vermont
United States	Tufts Medical Center	Boston	Massachusetts
United States	Clinical Research Professionals	Chesterfield	Missouri
United States	Great Lakes Clinical Trials	Chicago	Illinois
United States	Lindner Research Center	Cincinnati	Ohio
United States	Columbus Memory Center, PC	Columbus	Georgia
United States	Ohio State University Medical Center	Columbus	Ohio
United States	Baylor AT&T Memory Center	Dallas	Texas
United States	Neurology Consultants of Dallas, PA	Dallas	Texas
United States	University of Cincinnati Health Neurology	Dayton	Ohio
United States	Quantum Laboratories Clinical Research	Deerfield Beach	Florida
United States	Brain Matters Research	Delray Beach	Florida
United States	AMITA Health - Alexian Brothers Neurosciences Institute Clinical Research	Elk Grove Village	Illinois
United States	Pharmacology Research Institute	Encino	California
United States	Cognition Health	Fairfax	Virginia
United States	Neuropsychiatric Research Center of Southwest Florida	Fort Myers	Florida
United States	Fullerton Neurology and Headache Center	Fullerton	California
United States	Infinity Clinical Research, LLC	Hollywood	Florida
United States	Houston Methodist Research Ins	Houston	Texas
United States	Josephson Wallack Munshower Neurology, PC	Indianapolis	Indiana
United States	Irvine Clinical Research Center	Irvine	California
United States	Rowe Neurology Institute	Lenexa	Kansas
United States	Pharmacology Research Institute	Los Alamitos	California
United States	Suburban Research Associates	Media	Pennsylvania
United States	VIN-Victor Faradji	Miami	Florida
United States	Boston Center for Memory	Newton	Massachusetts
United States	Renstar Medical Research	Ocala	Florida
United States	BioClinica Inc	Orlando	Florida
United States	National Research Institute - Huntington Park	Panorama City	California
United States	Banner Alzheimer's Institute	Phoenix	Arizona
United States	Progressive Medical Research	Port Orange	Florida
United States	Butler Hospital	Providence	Rhode Island
United States	Raleigh Neurology Associates, P.A.	Raleigh	North Carolina
United States	Anderson Clinical Research	Redlands	California
United States	Pacific Research Network	San Diego	California
United States	Univ of California San Francisco	San Francisco	California
United States	Syrentis Clinical Research	Santa Ana	California
United States	The Cognitive and Research Center of New Jersey	Springfield	New Jersey
United States	New England Institute for Clinical Research	Stamford	Connecticut
United States	Brain Matters Research	Stuart	Florida
United States	Infinity Clinical Research, LLC	Sunrise	Florida
United States	Advanced Memory Research Institute of New Jersey	Toms River	New Jersey
United States	Cotton O'Neil Clinic	Topeka	Kansas
United States	Center for Neurosciences	Tucson	Arizona
United States	PMG Research of Winston-Salem, LLC	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Canada,  Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

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