A Study of LY3303560 in Participants With Early Symptomatic Alzheimer's Disease
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| ClinicalTrials.gov Identifier: NCT03518073 |
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Recruitment Status :
Completed
First Posted : May 8, 2018
Results First Posted : August 30, 2022
Last Update Posted : August 30, 2022
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Sponsor:
Eli Lilly and Company
Information provided by (Responsible Party):
Eli Lilly and Company
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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).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Alzheimer Disease (AD) | Drug: Zagotenemab Drug: Placebo | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 360 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Triple (Participant, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | Assessment of Safety, Tolerability, and Efficacy of LY3303560 in Early Symptomatic Alzheimer's Disease |
| Actual Study Start Date : | April 30, 2018 |
| Actual Primary Completion Date : | August 23, 2021 |
| Actual Study Completion Date : | October 25, 2021 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Alzheimer disease
MedlinePlus related topics:
Alzheimer's Disease
| Arm | Intervention/treatment |
|---|---|
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Placebo Comparator: Placebo
Participants received intravenous (IV) infusion of placebo once every four weeks (Q4W) for 100 weeks.
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Drug: Placebo
Administered IV |
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Experimental: Zagotenemab 1400 mg
Participants received IV infusion of 1400 milligram (mg) zagotenemab Q4W for 100 weeks.
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Drug: Zagotenemab
Administered IV
Other Name: LY3303560 |
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Experimental: Zagotenemab 5600 mg
Participants received IV infusion of 5600 mg zagotenemab Q4W for 100 weeks.
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Drug: Zagotenemab
Administered IV
Other Name: LY3303560 |
Primary Outcome Measures :
- Change From Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS) [ Time Frame: 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 :
- Change From Baseline on the Alzheimer's Disease Assessment Scale- Cognitive Subscale (ADAS-Cog13) Score [ Time Frame: 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 [ Time Frame: 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 on the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) Score [ Time Frame: 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 [ Time Frame: 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 Aggregated Tau Deposition as Measured by Flortaucipir F-18 Positron Emission Tomography (PET) Scan. [ Time Frame: 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.
- Change From Baseline in Brain Volume as Measured by Volumetric Magnetic Resonance Imaging (vMRI) [ Time Frame: 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.
- Number of Participants With Suicidal Ideation and Behaviors Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: 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 [ Time Frame: 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).
Information from the National Library of Medicine
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| Ages Eligible for Study: | 60 Years to 85 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03518073
Locations
Show 60 study locations
Sponsors and Collaborators
Eli Lilly and Company
Investigators
| Study Director: | Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) | Eli Lilly and Company |
Study Documents (Full-Text)
Documents provided by Eli Lilly and Company:
Documents provided by Eli Lilly and Company:
Study Protocol [PDF] March 29, 2021
Statistical Analysis Plan [PDF] October 11, 2021
Additional Information:
| Responsible Party: | Eli Lilly and Company |
| ClinicalTrials.gov Identifier: | NCT03518073 |
| Other Study ID Numbers: |
16124 I8G-MC-LMDC ( Other Identifier: Eli Lilly and Company ) |
| First Posted: | May 8, 2018 Key Record Dates |
| Results First Posted: | August 30, 2022 |
| Last Update Posted: | August 30, 2022 |
| Last Verified: | August 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| 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. |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Eli Lilly and Company:
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Memory problems Cognitive impairment PERISCOPE-ALZ |
Dementia Tauopathy Neurofibrillary tangles |
Additional relevant MeSH terms:
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Alzheimer Disease Dementia Brain Diseases Central Nervous System Diseases Nervous System Diseases |
Tauopathies Neurodegenerative Diseases Neurocognitive Disorders Mental Disorders |