Clinical Trial Results:
A 24-Month, Phase 3, Multicenter, Placebo-Controlled Study of Efficacy and Safety of Solanezumab versus Placebo in Prodromal Alzheimer’s Disease
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Summary
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EudraCT number |
2016-000108-27 |
Trial protocol |
BE PL DE NL GB ES |
Global end of trial date |
08 May 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
24 May 2018
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First version publication date |
24 May 2018
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
H8A-MC-LZBE
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02760602 | ||
WHO universal trial number (UTN) |
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Other trial identifiers |
Trial Number: 16349 | ||
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Sponsors
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Sponsor organisation name |
Eli Lilly and Company
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Sponsor organisation address |
Lilly Corporate Center, Indianapolis, IN, United States, 46285
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Public contact |
Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐CTLilly, clinicaltrials.gov@lilly.com
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Scientific contact |
Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐285‐4559, clinicaltrials.gov@lilly.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
08 May 2017
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
08 May 2017
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
The main purpose of this study is to investigate the safety and efficacy of the study drug solanezumab in participants with prodromal Alzheimer's disease (AD).
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Protection of trial subjects |
This study was conducted in accordance with International Conference on Harmonization (ICH) Good Clinical Practice, and the principles of the Declaration of Helsinki, in addition to following the laws and regulations of the country or countries in which a study is conducted.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
27 Jun 2016
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Canada: 1
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Country: Number of subjects enrolled |
Japan: 2
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Country: Number of subjects enrolled |
Poland: 2
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Country: Number of subjects enrolled |
United States: 21
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Worldwide total number of subjects |
26
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EEA total number of subjects |
2
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
2
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From 65 to 84 years |
24
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||||||
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Pre-assignment
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Screening details |
Participants were randomized by site and by use of florbetapir positron emission tomography (PET) scanning or cerebrospinal fluid (CSF) for study eligibility. | ||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||
Roles blinded |
Subject, Investigator, Carer | ||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Solanezumab | ||||||||||||||||||
Arm description |
Solanezumab given intravenously (IV) once every 4 weeks for up to 2 years. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Solanezumab
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Solanezumab 400 milligram (mg) given IV once every 4 weeks for up to 2 years.
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Arm title
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Placebo | ||||||||||||||||||
Arm description |
Placebo given IV once every 4 weeks for up to 2 years. | ||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Placebo given IV once every 4 weeks for up to 2 years.
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Baseline characteristics reporting groups
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Reporting group title |
Solanezumab
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Reporting group description |
Solanezumab given intravenously (IV) once every 4 weeks for up to 2 years. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Placebo given IV once every 4 weeks for up to 2 years. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Solanezumab
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Reporting group description |
Solanezumab given intravenously (IV) once every 4 weeks for up to 2 years. | ||
Reporting group title |
Placebo
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Reporting group description |
Placebo given IV once every 4 weeks for up to 2 years. | ||
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End point title |
Change from Baseline in Alzheimer´s Disease Assessment Scale- Cognitive Subscale (ADAS-Cog14) Score [1] | |||||||||
End point description |
ADAS-Cog14 is ADAS-Cog11 augmented with orientation, verbal memory, language, praxis, delayed free recall, digit cancellation, and maze-completion measures. The ADAS-Cog14 scale ranges from 0 to 90. Higher scores indicate greater disease severity.
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End point type |
Primary
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End point timeframe |
Baseline, 24 Months
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Zero participants were analyzed due to trial termination. Therefore, no inferential statistics were planned or conducted for this endpoint. |
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| Notes [2] - Zero participants were analyzed due to trial termination. [3] - Zero participants were analyzed due to trial termination. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Change from Baseline on Alzheimer´s Disease Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS-MCI-ADL) | |||||||||
End point description |
The ADCS-MCI-ADL is a functional evaluation scale for MCI patients, based on information provided by an informant that describes the performance of participants in several ADLs. Total score ranges from 0 to 69; lower score indicates greater disease severity.
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End point type |
Secondary
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End point timeframe |
Baseline, 24 Months
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| Notes [4] - Zero participants were analyzed due to trial termination. [5] - Zero participants were analyzed due to trial termination. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Change from Baseline on the Mini Mental Status Examination (MMSE) | |||||||||
End point description |
MMSE is a brief screening instrument used to assess cognitive function (orientation, memory, attention, ability to name objects, follow verbal/written commands, write a sentence, and copy figures) in elderly participants.Total score ranges from 0 to 30; lower score indicates greater disease severity.
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End point type |
Secondary
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End point timeframe |
Baseline, 24 Months
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| Notes [6] - Zero participants were analyzed due to trial termination. [7] - Zero participants were analyzed due to trial termination. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Change from Baseline on the Montreal Cognitive Assessment (MoCA) | |||||||||
End point description |
The MoCA will be used as the global cognitive screening instrument. It will also be administered in the clinical trial at baseline and the final visits of each phase as a secondary outcome measure of global cognition. Scores on the MoCA range from 0-30 with 26-30 indicating normal global cognition.
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End point type |
Secondary
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End point timeframe |
Baseline, 24 Months
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| Notes [8] - Zero participants were analyzed due to trial termination. [9] - Zero participants were analyzed due to trial termination. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Change from Baseline on the Functional Activities Questionnaire (FAQ) | |||||||||
End point description |
FAQ is a 10-item, caregiver-based questionnaire and was administered to the study partner who was asked to rate the participant’s ability to perform a variety of activities ranging from Writing checks, Assembling tax records, shopping, playing games, food preparation, traveling, keeping appointments, Traveling out of neighborhood, keeping track of current events and understanding media. FAQ total score was calculated by adding the scores from each of the 10 items. Each activity is rated on a scale from 0 to 3 (Never did and would have difficulty now = 1; Never did [the activity] but could do now = 0; Normal = 0; Has difficulty but does by self = 1; Requires assistance = 2; Dependent = 3). The maximum FAQ total score is 30, with higher scores indicating greater impairment.
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End point type |
Secondary
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End point timeframe |
Baseline, 24 Months
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| Notes [10] - Zero participants were analyzed due to trial termination. [11] - Zero participants were analyzed due to trial termination. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Change from Baseline on the Neuropsychiatric Inventory (NPI) | |||||||||
End point description |
The NPI is a tool for assessing psychopathology in participants with dementia and other neurologic disorders. Information is obtained from a caregiver familiar with the participant’s behavior. The score ranges from 0 to 144, with higher scores indicating greater disease severity.
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End point type |
Secondary
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End point timeframe |
Baseline, 24 Months
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| Notes [12] - Zero participants were analyzed due to trial termination. [13] - Zero participants were analyzed due to trial termination. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Change from Baseline on the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) | |||||||||
End point description |
CDR-SB is a semi-structured interview of participants and their caregivers. Participant's cognitive status is rated across 6 domains of functioning, including 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.
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End point type |
Secondary
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End point timeframe |
Baseline, 24 Months
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| Notes [14] - Zero participants were analyzed due to trial termination. [15] - Zero participants were analyzed due to trial termination. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Change from Baseline on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) | |||||||||
End point description |
RBANS is a brief neurocognitive battery with four alternate forms, measuring immediate and delayed memory, attention, language, and visuospatial/constructional skills.
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End point type |
Secondary
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End point timeframe |
Baseline, 24 Months
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| Notes [16] - Zero participants were analyzed due to trial termination. [17] - Zero participants were analyzed due to trial termination. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Change from Baseline on the Free and Cued Selective Reminding Test (FCSRT) | |||||||||
End point description |
The FCSRT is a neuropsychological test of memory under conditions that control attention and cognitive processing in order to obtain an assessment of memory unconfounded by normal age-related changes in cognition.
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End point type |
Secondary
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End point timeframe |
Baseline, 24 Months
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| Notes [18] - Zero participants were analyzed due to trial termination. [19] - Zero participants were analyzed due to trial termination. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Change from Baseline on the Resource Utilization in Dementia–Lite (RUD-Lite) | |||||||||
End point description |
RUD-Lite assesses the healthcare resource utilization of participants and their caregivers to determine the level of formal and informal care attributable to Alzheimer's Disease (AD). Information on both caregivers (caregiving time, work status) and participants (accommodation and healthcare resource utilization) is collected from the baseline and follow-up interviews.
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End point type |
Secondary
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End point timeframe |
Baseline, 24 Months
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| Notes [20] - Zero participants were analyzed due to trial termination. [21] - Zero participants were analyzed due to trial termination. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Change from Baseline on the EuroQol 5-Dimensional Health-Related Quality of Life Scale (EQ-5D) | |||||||||
End point description |
EQ-5D (proxy version) measures mobility, self-care, usual activities, pain/discomfort, anxiety/depression; each has 3 severity levels (no, some, severe problems) coded to a 1-digit number (1-3). Digits are combined into 5-digit number describing health state. Visual analogue scale (VAS) assesses caregiver's impression of participant's overall health state; scores range: 0 to 100. Lower scores indicate greater disease severity.
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End point type |
Secondary
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End point timeframe |
Baseline, 24 Months
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| Notes [22] - Zero participants were analyzed due to trial termination. [23] - Zero participants were analyzed due to trial termination. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Change from Baseline on the Quality of Life in Alzheimer’s Disease Scale (QoL-AD) | |||||||||
End point description |
QoL for AD assess participant rates mood, relationships, memory, finances, physical condition, and overall QoL assessment. Each of 13 items rated on a 4-point scale. Sum of items=total score (range: 13-52). Higher scores=greater QoL.
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End point type |
Secondary
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End point timeframe |
Baseline, 24 Months
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| Notes [24] - Zero participants were analyzed due to trial termination. [25] - Zero participants were analyzed due to trial termination. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Change from Baseline in Concentration of Plasma Amyloid-β Peptide (Aβ) and Plasma Solanezumab | |||||||||
End point description |
Concentration of amino acid peptide known as Aβ 1-42 in plasma.
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End point type |
Secondary
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End point timeframe |
Baseline, 24 Months
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| Notes [26] - Zero participants were analyzed due to trial termination. [27] - Zero participants were analyzed due to trial termination. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Change from Baseline in Volumetric Magnetic Resonance Imaging (vMRI) | |||||||||
End point description |
MRI will be used to assess the effect of treatment on rate of whole brain volume.
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End point type |
Secondary
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End point timeframe |
Baseline, 24 Months
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| Notes [28] - Zero participants were analyzed due to trial termination. [29] - Zero participants were analyzed due to trial termination. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Change from Baseline in Florbetapir Positron Emission Tomography (PET) Standardized Uptake Value Ratio (SUVr) | |||||||||
End point description |
Florbetapir F18 PET used to assess the treatment effect in brain amyloid plaque deposition from baseline through 18 months as measured by florbetapir F18 PET Standardized Uptake Uptake Value ratio.
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End point type |
Secondary
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End point timeframe |
Baseline, 24 Months
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| Notes [30] - Zero participants were analyzed due to trial termination. [31] - Zero participants were analyzed due to trial termination. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Change from Baseline in Concentration of Cerebrospinal Fluid (CSF) Aβ and CSF Tau Proteins | |||||||||
End point description |
Changes in CSF parameters, including total and free Aβ1-40 and Aβ1-42 species and total tau and P-tau181 peptides, will be assessed.
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End point type |
Secondary
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End point timeframe |
Baseline, 24 Months
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| Notes [32] - Zero participants were analyzed due to trial termination. [33] - Zero participants were analyzed due to trial termination. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Change from Baseline in Neocortical Tau Deposits using 18F-AV-1451 PET | |||||||||
End point description |
Biomarker change will be analyzed to provide biomarker-based evidence that solanezumab affects the underlying disease pathology.
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End point type |
Secondary
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End point timeframe |
Baseline, 24 Months
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| Notes [34] - Zero participants were analyzed due to trial termination. [35] - Zero participants were analyzed due to trial termination. |
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| No statistical analyses for this end point | ||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Entire Study
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Adverse event reporting additional description |
H8A-MC-LZBE
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20.0
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Reporting groups
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Reporting group title |
Solanezumab 400 mg
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| The study was terminated due to insufficient scientific evidence that solanezumab would likely demonstrate a meaningful benefit to participants with prodromal AD as defined by the study protocol. | |||
