A Study of LY3303560 in Participants With Early Symptomatic Alzheimer's Disease
- Registration Number
- NCT03518073
- Lead Sponsor
- Eli Lilly and Company
- Brief 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 360
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Participants received intravenous (IV) infusion of placebo once every four weeks (Q4W) for 100 weeks. Zagotenemab 5600 mg Zagotenemab Participants received IV infusion of 5600 mg zagotenemab Q4W for 100 weeks. Zagotenemab 1400 mg Zagotenemab Participants received IV infusion of 1400 milligram (mg) zagotenemab Q4W for 100 weeks.
- Primary Outcome Measures
Name Time Method Change From Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS) Baseline, Week 104 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.
- Secondary Outcome Measures
Name Time Method Change From Baseline on the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) Score Baseline, Week 104 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.
Change From Baseline on the Mini Mental Status Examination (MMSE) Score Baseline, Week 104 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.
Change From Baseline in Brain Volume as Measured by Volumetric Magnetic Resonance Imaging (vMRI) Baseline, Week 104 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.
Change From Baseline on the Alzheimer's Disease Assessment Scale- Cognitive Subscale (ADAS-Cog13) Score Baseline, Week 104 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.
Change From Baseline on the Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living Scale (ADCS-iADL) Score Baseline, Week 104 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.
Change From Baseline in Brain Aggregated Tau Deposition as Measured by Flortaucipir F-18 Positron Emission Tomography (PET) Scan. Baseline, Week 104 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.
Number of Participants With Suicidal Ideation and Behaviors Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) Baseline through Week 104 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.Number of Participants With Treatment Emergent Anti-Drug Antibodies (TE-ADA) to Zagotenemab Baseline through Week 113 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).
Trial Locations
- Locations (57)
Q&T Research Sherbrooke Inc.
🇨🇦Sherbrooke, Quebec, Canada
Syrentis Clinical Research
🇺🇸Santa Ana, California, United States
Pharmacology Research Institute
🇺🇸Los Alamitos, California, United States
Irvine Clinical Research Center
🇺🇸Irvine, California, United States
Fullerton Neurology and Headache Center
🇺🇸Fullerton, California, United States
New England Institute for Clinical Research
🇺🇸Stamford, Connecticut, United States
Columbus Memory Center, PC
🇺🇸Columbus, Georgia, United States
Baylor AT&T Memory Center
🇺🇸Dallas, Texas, United States
University of Cincinnati Health Neurology
🇺🇸Dayton, Ohio, United States
Suburban Research Associates
🇺🇸Media, Pennsylvania, United States
Clinical Research Professionals
🇺🇸Chesterfield, Missouri, United States
Anderson Clinical Research
🇺🇸Redlands, California, United States
Cognition Health
🇺🇸Fairfax, Virginia, United States
Lehigh Center for Clinical Research
🇺🇸Allentown, Pennsylvania, United States
Neurology Consultants of Dallas, PA
🇺🇸Dallas, Texas, United States
Houston Methodist Research Ins
🇺🇸Houston, Texas, United States
National Research Institute - Huntington Park
🇺🇸Panorama City, California, United States
Renstar Medical Research
🇺🇸Ocala, Florida, United States
Great Lakes Clinical Trials
🇺🇸Chicago, Illinois, United States
Ohio State University Medical Center
🇺🇸Columbus, Ohio, United States
Butler Hospital
🇺🇸Providence, Rhode Island, United States
Rowe Neurology Institute
🇺🇸Lenexa, Kansas, United States
Cotton O'Neil Clinic
🇺🇸Topeka, Kansas, United States
Julie B. Schwartzbard, MD, PA
🇺🇸Aventura, Florida, United States
Quantum Laboratories Clinical Research
🇺🇸Deerfield Beach, Florida, United States
Brain Matters Research
🇺🇸Stuart, Florida, United States
Toronto Memory Program
🇨🇦Toronto, Ontario, Canada
Infinity Clinical Research, LLC
🇺🇸Sunrise, Florida, United States
Progressive Medical Research
🇺🇸Port Orange, Florida, United States
Boston Center for Memory
🇺🇸Newton, Massachusetts, United States
National Center for Geriatrics and Gerontology
🇯🇵Obu City, Aichi, Japan
Nippon Medical School Hospital
🇯🇵Tokyo, Jp-13, Japan
National hospital Organization Utano National Hospital
🇯🇵Kyoto, Jp-26, Japan
Advanced Memory Research Institute of New Jersey
🇺🇸Toms River, New Jersey, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Kawartha Centre - Redefining Healthy Aging
🇨🇦Peterborough, Ca-on, Canada
Center for Neurosciences
🇺🇸Tucson, Arizona, United States
Neuropsychiatric Research Center of Southwest Florida
🇺🇸Fort Myers, Florida, United States
Pharmasite Research, Inc.
🇺🇸Baltimore, Maryland, United States
NeuroSearch Developements
🇨🇦Greenfield Park, Quebec, Canada
JEM Research Institute
🇺🇸Atlantis, Florida, United States
The Cognitive and Research Center of New Jersey
🇺🇸Springfield, New Jersey, United States
The Memory Clinic
🇺🇸Bennington, Vermont, United States
Kobe City Medical Center General Hospital
🇯🇵Kobe, Hyogo, Japan
Shonan Kamakura General Hospital
🇯🇵Kamakura, Kanagawa, Japan
Katayama Medical Clinic
🇯🇵Kurashiki, Jp-33, Japan
Raleigh Neurology Associates, P.A.
🇺🇸Raleigh, North Carolina, United States
AMITA Health - Alexian Brothers Neurosciences Institute Clinical Research
🇺🇸Elk Grove Village, Illinois, United States
Univ of California San Francisco
🇺🇸San Francisco, California, United States
BioClinica Inc
🇺🇸Orlando, Florida, United States
Banner Alzheimer's Institute
🇺🇸Phoenix, Arizona, United States
Pacific Research Network
🇺🇸San Diego, California, United States
Josephson Wallack Munshower Neurology, PC
🇺🇸Indianapolis, Indiana, United States
PMG Research of Winston-Salem, LLC
🇺🇸Winston-Salem, North Carolina, United States
VIN-Victor Faradji
🇺🇸Miami, Florida, United States
Lindner Research Center
🇺🇸Cincinnati, Ohio, United States
Clinique de la Mémoire de l'Outaouais
🇨🇦Gatineau, Quebec, Canada