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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT02956486
Registration number
NCT02956486
Ethics application status
Date submitted
3/11/2016
Date registered
6/11/2016
Date last updated
3/02/2021
Titles & IDs
Public title
A 24-Month Study to Evaluate the Efficacy and Safety of Elenbecestat (E2609) in Participants With Early Alzheimer's Disease
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Scientific title
A Placebo-Controlled, Double-Blind, Parallel-Group, 24 Month Study With an Open-Label Extension Phase to Evaluate the Efficacy and Safety of Elenbecestat (E2609) in Subjects With Early Alzheimer's Disease
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Secondary ID [1]
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2016-003928-23
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Secondary ID [2]
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E2609-G000-301
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Universal Trial Number (UTN)
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Trial acronym
MissionAD1
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Alzheimer's Disease
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Condition category
Condition code
Neurological
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Alzheimer's disease
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Neurological
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Dementias
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Elenbecestat
Treatment: Drugs - Placebo
Experimental: Core Study: Elenbecestat 50 mg - Participants will receive one 50 milligram (mg) elenbecestat tablet, orally, once a day in the morning. The core study will be double blinded.
Placebo Comparator: Core Study: Placebo - Participants will receive one matching placebo tablet, orally, once a day in the morning. The core study will be double blinded.
Experimental: Open-label Extension Phase: Elenbecestat 50 mg - Participants completing the core study will receive one 50 mg elenbecestat tablet, orally, once a day in the morning.
Treatment: Drugs: Elenbecestat
Oral tablet.
Treatment: Drugs: Placebo
Oral tablet.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Core Phase: Change From Baseline up to Month 24 in the Clinical Dementia Rating-sum of Boxes (CDR-SB) Score
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Assessment method [1]
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The clinical dementia rating (CDR) scale is a clinical global rating scale that requires interviewing both the participant and an informant who knows and has contact with the participant. The CDR scale is a clinician directed assessment of both cognition and function, and is intended to capture the state and therefore the disease stage of the participant. The CDR scale assesses 6 domains of participant function (memory, orientation, judgement and problem solving, community affairs, home and hobbies and personal care) on a 5-point scale in which no impairment=0, questionable impairment=0.5, mild impairment=1, moderate impairment=2 and severe impairment=3. The CDR-SB is a sum of the individual domain scores and ranges from 0 to 18. Higher score indicates more impairment.
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Timepoint [1]
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Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase
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Primary outcome [2]
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Extension Phase: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
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Assessment method [2]
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A TEAE is defined as an adverse event that emerged during treatment or within 28 days following the last dose of study drug, having been absent at pretreatment (Baseline) or reemerged during treatment, having been present at pretreatment (Baseline) but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the adverse event was continuous. Number of participants with TEAEs (serious and non-serious adverse events) were reported based on their safety assessments of laboratory tests, suicidal ideation and suicidal behavior, drug abuse potential, physical examination, neurological examination, regular measurement of vital signs, magnetic resonance imaging and electrocardiogram parameter values.
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Timepoint [2]
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From first dose of study drug up to approximately 6 months (including 1 month follow up) for the extension phase
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Secondary outcome [1]
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Core Phase: Change From Baseline up to Month 24 in Alzheimer's Disease Composite Score (ADCOMS)
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Assessment method [1]
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ADCOMS is a weighted linear combination of 12 items from three existing clinical scales: the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), the Mini Mental State Examination (MMSE), and the CDR. Four items are from the ADAS-cog (A4 [Delayed Word Recall], A7 [Orientation], A8 [Word Recognition], A11 [Word Finding]); 2 items are from the MMSE (M1 [Orientation Time], M7 [Drawing]); 6 items are from the CDR (C1 [Personal Care], C2 [Community Affairs], C3 [Home and Hobbies], C4 [Judgment and Problem Solving], C5 [Memory], C6 [Orientation]). Composite score is derived from the variables from the 12 items, and ranges from 0 to 1.97, where higher score indicates worse performance.
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Timepoint [1]
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Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase
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Secondary outcome [2]
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Core Phase: Change From Baseline up to Month 24 in Amyloid Positron Emission Tomography (PET) Standardized Uptake Value Ratio (SUVR)
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Assessment method [2]
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Amyloid PET scan assesses cerebral amyloid load using 3 tracers (florbetapir, florbetaben and flutemetamol) which is standardized into centiloids for evaluation of AD. Centiloid values on centiloid scale is based on mean composite SUVR in cingulate, frontal, parietal and temporal cortexes using whole cerebellum as reference region. SUVR is ratio of tracer uptake in each of cingulate, frontal, parietal and temporal cortexes relative to cerebellum. The centiloid scale anchor points are 0 and 100, where 0 represents a high-certainty amyloid negative scan and 100 represents the amount of global amyloid deposition found in a typical AD scans.
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Timepoint [2]
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Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase
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Secondary outcome [3]
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Core Phase: Change From Baseline up to Month 24 in the CDR-SB Score for Participants Enriched by Baseline Amyloid PET SUVR Between 1.2 and 1.6
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Assessment method [3]
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0
The CDR scale is a clinical global rating scale that requires interviewing both the participant and an informant who knows and has contact with the participant. The CDR scale is a clinician directed assessment of both cognition and function, and is intended to capture the state and therefore the disease stage of the participant. The CDR scale assesses 6 domains of participant function (memory, orientation, judgement and problem solving, community affairs, home and hobbies and personal care) on a 5-point scale in which no impairment=0, questionable impairment=0.5, mild impairment=1, moderate impairment=2 and severe impairment=3. The CDR-SB is a sum of the individual domain scores and ranges from 0 to 18. Higher score indicates more impairment. Amyloid PET scans allow in vivo assessment of cerebral amyloid load. SUVR indicates the ratio of tracer uptake in the frontal cortex relative to the cerebellum or the ratio of tracer uptake in the whole brain relative to the cerebellum.
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Timepoint [3]
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Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase
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Secondary outcome [4]
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Core Phase: Change From Baseline up to Month 24 in the ADCOMS for Participants Enriched by Baseline Amyloid PET SUVR Between 1.2 and 1.6
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Assessment method [4]
0
0
ADCOMS is a weighted linear combination of 12 items from three existing clinical scales: the ADAS-cog, the MMSE, and the CDR. Four items are from the ADAS-cog (A4 [Delayed Word Recall], A7 [Orientation], A8 [Word Recognition], A11 [Word Finding]); 2 items are from the MMSE (M1 [Orientation Time], M7 [Drawing]); 6 items are from the CDR (C1 [Personal Care], C2 [Community Affairs], C3 [Home and Hobbies], C4 [Judgment and Problem Solving], C5 [Memory], C6 [Orientation]). Composite score is derived from the variables from the 12 items, and ranges from 0 to 1.97, where higher score indicates worse performance. Amyloid PET scans allow in vivo assessment of cerebral amyloid load. SUVR indicates the ratio of tracer uptake in the frontal cortex relative to the cerebellum or the ratio of tracer uptake in the whole brain relative to the cerebellum.
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Timepoint [4]
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Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase
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Secondary outcome [5]
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Core Phase: Change Per Year (Mean Slope) in CDR-SB Score up to Month 24
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Assessment method [5]
0
0
The CDR scale is a clinical global rating scale that requires interviewing both the participant and an informant who knows and has contact with the participant. The CDR scale is a clinician directed assessment of both cognition and function, and is intended to capture the state and therefore the disease stage of the participant. The CDR scale assesses 6 domains of participant function (memory, orientation, judgement and problem solving, community affairs, home and hobbies and personal care) on a 5-point scale in which no impairment=0, questionable impairment=0.5, mild impairment=1, moderate impairment=2 and severe impairment=3. The CDR-SB is a sum of the individual domain scores and ranges from 0 to 18. Higher score indicates more impairment. In this outcome measure, change per year (mean slope) in CDR-SB score was calculated up to month 24, where higher change indicated more impairment and lower change indicated less impairment.
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Timepoint [5]
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Up to Month 24 of the core phase
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Secondary outcome [6]
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Core Phase: Time to Worsening of CDR Score up to Month 24
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Assessment method [6]
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0
The CDR scale is a clinical global rating scale that requires interviewing both the participant and an informant who knows and has contact with the participant. The CDR scale is a clinician directed assessment of both cognition and function, and is intended to capture the state and therefore the disease stage of the participant. The CDR scale assesses 6 domains of participant function (memory, orientation, judgement and problem solving, community affairs, home and hobbies and personal care) on a 5-point scale in which no impairment=0, questionable impairment=0.5, mild impairment=1, moderate impairment=2 and severe impairment=3. The global CDR score is computed via an algorithm and ranges from 0 to 3. Higher score indicates more impairment. In this outcome measure, time (in months) to worsening of CDR score (that is, an increase from baseline by at least 0.5 points on the global CDR scale on 2 consecutive scheduled visits) up to month 24 was calculated.
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Timepoint [6]
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Up to Month 24 of the core phase
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Secondary outcome [7]
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Core Phase: Time to Conversion to Dementia for Participants Who Were Not Clinically Staged as Having Dementia at the Core Phase Baseline up to Month 24
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Assessment method [7]
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Time (in months) to conversion to dementia for participants who were not clinically staged as having dementia at the core phase baseline (that is time from randomization to conversion to dementia in clinical diagnosis).
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Timepoint [7]
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Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase
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Secondary outcome [8]
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Core Phase: Change From Baseline up to Month 24 in the Alzheimer's Disease Assessment Scale-cognition14 (ADAS-Cog14) Score
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Assessment method [8]
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ADAS-cog14 is a psychometric instrument that evaluates 14-items (Immediate Word-recall [0-10], Commands [0-5], Constructional Praxis [0-5], Delayed Word-recall [0-10], Naming Objects/Fingers [0-5], Ideational Praxis [0-5], Orientation[0-8], Word Recognition [0-12], Remembering Test Instructions [0-5], Comprehension[0-5], Word Finding Difficulty [0-5], Spoken Language Ability [0-5], Executive Function [0-5], and Number Cancellation [0-5] test). It is considered to be more sensitive for less impaired populations such as MCI/Prodromal and mild AD participants. The total score ranges from 0 to 90. Higher score indicates more impairment.
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Timepoint [8]
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0
Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase
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Secondary outcome [9]
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Core Phase: Change From Baseline up to Month 24 in the MMSE Score
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Assessment method [9]
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0
The MMSE is a cognitive instrument commonly used for screening purposes, for staging of disease severity and is often measured longitudinally in AD clinical studies to follow disease progression and treatment effects. MMSE is composed of 30 questions grouped into domains (Orientation to Time [0-5], Orientation to Place [0-5], Registration [0-3], Attention and Calculation [0-5], Recall [0-3], Naming [0-2], Repetition [0-1], Comprehension [0-3], Reading [0-1], Writing [0-1], Drawing [0-1]). For each of the MMSE domains, six items are computed (Orientation to Time [0-5], Orientation to Place [0-5], Registration [0-3], Attention and Calculation [0-5], Recall [0-3], Language: Naming, Repetition, Comprehension, Reading, Writing, and Drawing [0-9]). The MMSE Total Score is the sum of the six domains and ranges from 0 to 30. If any domain score was missing then the total score was missing. Higher score indicates better function.
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Timepoint [9]
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0
Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase
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Secondary outcome [10]
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Core Phase: Change From Baseline up to Month 24 in the Functional Assessment Questionnaire (FAQ) Score
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Assessment method [10]
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FAQ scores 10 items & measures activities of daily living (paying bills/balancing checkbook, assembling tax records, shopping alone for clothes or groceries, playing game of skill such as bridge or chess/working on a hobby, heating water & turning off stove, preparing balanced meal, keeping track of current events, paying attention & understanding television program, remembering appointments, driving or traveling out of neighborhood). Each item is rated as follows: 0=Normal, 1=Has difficulty but does by self, 2=Requires assistance, 3=Dependent, or 8=Not Applicable. The total score is the sum of all 10 items & ranges from 0 to 30. Higher score indicates more impairment. If any activity was missed, then the total score was missed. Activities rated as "Not Applicable" were not used in the computation of the total score. To account for "Not Applicable" activity, the total score was weighted as:Total Score=Total Score*30/(30 minus 3 times the number of activities marked"Not Applicable").
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Timepoint [10]
0
0
Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase
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Secondary outcome [11]
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0
Core Phase: Change From Baseline up to Month 24 in the ADAS-cog14 Word List (Immediate Recall and Delayed Recall) Score
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Assessment method [11]
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0
The ADAS-cog14 Word List is a summation of two items: "Immediate Word-recall" and "Delayed Word-recall". Immediate Word-recall test: Participants are asked to recall words and the number of "No" responses for each trial (total 3 trials) are summed. Subscore: sum of scores from 3 trials, divided by 3. Score ranges from 0 to 10. Delayed Word-recall: Participants used to recall words after a delay and the number of "No" responses are summed. Score ranges from 0 to 10. The Total Score ranges from 0 to 20. Higher score indicates more impairment.
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Timepoint [11]
0
0
Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase
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Secondary outcome [12]
0
0
Core Phase: Change From Baseline up to Month 24 in the Alzheimer's Disease Assessment Scale-cognition11 (ADAS-Cog11) Score
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Assessment method [12]
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0
ADAS-cog11 is a psychometric instrument that evaluates 11-items (Immediate Word-recall [0 to 10], Commands [0-5], Constructional Praxis [0-5], Naming Objects/Fingers [0-5], Ideational Praxis [0-5], Orientation[0-8], Word Recognition [0-12], Remembering Test Instructions [0-5], Comprehension[0-5], Word Finding Difficulty [0-5], Spoken Language Ability [0-5] test) and is considered more sensitive for less impaired populations such as MCI/Prodromal and mild AD participants. The Total score ranges from 0 to 70. Higher score indicates more impairment.
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Timepoint [12]
0
0
Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase
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Secondary outcome [13]
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0
Core Phase: Change From Last Dose in the CDR-SB Score
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Assessment method [13]
0
0
The CDR scale is a clinical global rating scale that requires interviewing both the participant and an informant who knows and has contact with the participant. The CDR scale is a clinician directed assessment of both cognition and function, and is intended to capture the state and therefore the disease stage of the participant. The CDR scale assesses 6 domains of participant function (memory, orientation, judgement and problem solving, community affairs, home and hobbies and personal care) on a 5-point scale in which no impairment=0, questionable impairment=0.5, mild impairment=1, moderate impairment=2 and severe impairment=3. The CDR-SB is a sum of the individual domain scores and ranges from 0 to 18. Higher score indicates more impairment.
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Timepoint [13]
0
0
From last dose in the core phase (up to Month 24) up to 3 months follow up (up to Month 27)
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Secondary outcome [14]
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Core Phase: Change From Last Dose in the ADCOMS
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Assessment method [14]
0
0
ADCOMS is a weighted linear combination of 12 items from three existing clinical scales: the ADAS-cog, the MMSE, and the CDR. Four items are from the ADAS-cog (A4 [Delayed Word Recall], A7 [Orientation], A8 [Word Recognition], A11 [Word Finding]); 2 items are from the MMSE (M1 [Orientation Time], M7 [Drawing]); 6 items are from the CDR (C1 [Personal Care], C2 [Community Affairs], C3 [Home and Hobbies], C4 [Judgment and Problem Solving], C5 [Memory], C6 [Orientation]). Composite score is derived from the variables from the 12 items, and ranges from 0 to 1.97, where higher score indicates worse performance.
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Timepoint [14]
0
0
From last dose in the core phase (up to Month 24) up to 3 months follow-up (up to Month 27)
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Secondary outcome [15]
0
0
Core Phase: Change From Last Dose in the ADAS-cog11 Score
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Assessment method [15]
0
0
ADAS-cog11 is a psychometric instrument that evaluates 11-items (Immediate Word-recall [0 to 10], Commands [0-5], Constructional Praxis [0-5], Naming Objects/Fingers [0-5], Ideational Praxis [0-5], Orientation[0-8], Word Recognition [0-12], Remembering Test Instructions [0-5], Comprehension[0-5], Word Finding Difficulty [0-5], Spoken Language Ability [0-5] test) and is considered more sensitive for less impaired populations such as MCI/Prodromal and mild AD participants. The Total score ranges from 0 to 70. Higher score indicates more impairment.
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Timepoint [15]
0
0
From last dose in the core phase (up to Month 24) up to 3 months follow-up (up to Month 27)
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Secondary outcome [16]
0
0
Core Phase: Change From Last Dose in the ADAS-cog14 Score
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Assessment method [16]
0
0
ADAS-cog14 is a psychometric instrument that evaluates 14-items (Immediate Word-recall [0 to 10], Commands [0-5], Constructional Praxis [0-5], Delayed Word-recall [0-10], Naming Objects/Fingers [0-5], Ideational Praxis [0-5], Orientation[0-8], Word Recognition [0-12], Remembering Test Instructions [0-5], Comprehension[0-5], Word Finding Difficulty [0-5], Spoken Language Ability [0-5], Executive Function [0-5], and Number Cancellation [0-5] test). It is considered to be more sensitive for less impaired populations such as MCI/Prodromal and mild AD participants. The Total Score ranges from 0 to 90. Higher score indicates more impairment.
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Timepoint [16]
0
0
From last dose in the core phase (up to Month 24) up to 3 months follow-up (up to Month 27)
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Secondary outcome [17]
0
0
Core Phase: Change From Last Dose in the MMSE Score
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Assessment method [17]
0
0
The MMSE is a cognitive instrument commonly used for screening purposes, for staging of disease severity and is often measured longitudinally in AD clinical studies to follow disease progression and treatment effects. MMSE is composed of 30 questions grouped into domains (Orientation to Time [0-5], Orientation to Place [0-5], Registration [0-3], Attention and Calculation [0-5], Recall [0-3], Naming [0-2], Repetition [0-1], Comprehension [0-3], Reading [0-1], Writing [0-1], Drawing [0-1]). For each of the MMSE domains, six items are computed (Orientation to Time [0-5], Orientation to Place [0-5], Registration [0-3], Attention and Calculation [0-5], Recall [0-3], Language: Naming, Repetition, Comprehension, Reading, Writing, and Drawing [0-9]). The MMSE Total Score is the sum of the six domains and ranges from 0 to 30. If any domain score was missing then the total score was missing. Higher score indicates better function.
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Timepoint [17]
0
0
From last dose in the core phase (up to Month 24) up to 3 months follow-up (up to Month 27)
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Secondary outcome [18]
0
0
Core Phase: Change From Last Dose in the ADAS-cog14 Word List (Immediate Recall and Delayed Recall) Score
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Assessment method [18]
0
0
The ADAS-cog14 Word List is a summation of two items: "Immediate Word-recall" and "Delayed Word-recall". Immediate Word-recall test: Participants are asked to recall words and the number of "No" responses for each trial (total 3 trials) are summed. Subscore: sum of scores from 3 trials, divided by 3. Score ranges from 0 to 10. Delayed Word-recall: Participants used to recall words after a delay and the number of "No" responses are summed. Score ranges from 0 to 10. The Total Score ranges from 0 to 20. Higher score indicates more impairment.
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Timepoint [18]
0
0
From last dose in the core phase (up to Month 24) up to 3 months follow-up (up to Month 27)
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Secondary outcome [19]
0
0
Extension Phase: Change From Core Phase Baseline up to Month 12 of the Extension Phase in CDR-SB Score
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Assessment method [19]
0
0
The CDR scale is a clinical global rating scale that requires interviewing both the participant and an informant who knows and has contact with the participant. The CDR scale is a clinician directed assessment of both cognition and function, and is intended to capture the state and therefore the disease stage of the participant. The CDR scale assesses 6 domains of participant function (memory, orientation, judgement and problem solving, community affairs, home and hobbies and personal care) on a 5-point scale in which no impairment=0, questionable impairment=0.5, mild impairment=1, moderate impairment=2 and severe impairment=3. The CDR-SB is a sum of the individual domain scores and ranges from 0 to 18. Higher score indicates more impairment.
Query!
Timepoint [19]
0
0
Baseline (Day 1: before first dose in the core phase) up to Month 12 of the extension phase
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Secondary outcome [20]
0
0
Extension Phase: Change From Core Phase Baseline up to Month 12 of the Extension Phase in ADCOMS
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Assessment method [20]
0
0
ADCOMS is a weighted linear combination of 12 items from three existing clinical scales: the ADAS-cog, the MMSE, and the CDR. Four items are from the ADAS-cog (A4 [Delayed Word Recall], A7 [Orientation], A8 [Word Recognition], A11 [Word Finding]); 2 items are from the MMSE (M1 [Orientation Time], M7 [Drawing]); 6 items are from the CDR (C1 [Personal Care], C2 [Community Affairs], C3 [Home and Hobbies], C4 [Judgment and Problem Solving], C5 [Memory], C6 [Orientation]). Composite score is derived from the variables from the 12 items, and ranges from 0 to 1.97, where higher score indicates worse performance.
Query!
Timepoint [20]
0
0
Baseline (Day 1: before first dose in the core phase) up to Month 12 of the extension phase
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Secondary outcome [21]
0
0
Extension Phase: Change From Core Phase Baseline up to Month 12 of the Extension Phase in MMSE Score
Query!
Assessment method [21]
0
0
The MMSE is a cognitive instrument commonly used for screening purposes, for staging of disease severity and is often measured longitudinally in AD clinical studies to follow disease progression and treatment effects. MMSE is composed of 30 questions grouped into domains (Orientation to Time [0-5], Orientation to Place [0-5], Registration [0-3], Attention and Calculation [0-5], Recall [0-3], Naming [0-2], Repetition [0-1], Comprehension [0-3], Reading [0-1], Writing [0-1], Drawing [0-1]). For each of the MMSE domains, six items are computed (Orientation to Time [0-5], Orientation to Place [0-5], Registration [0-3], Attention and Calculation [0-5], Recall [0-3], Language: Naming, Repetition, Comprehension, Reading, Writing, and Drawing [0-9]). The MMSE Total Score is the sum of the six domains and ranges from 0 to 30. If any domain score is missing then the total score is missing. Higher score indicates better function.
Query!
Timepoint [21]
0
0
Baseline (Day 1: before first dose in the core phase) up to Month 12 of the extension phase
Query!
Secondary outcome [22]
0
0
Extension Phase: Change From Core Phase Baseline up to Month 12 of the Extension Phase in FAQ Score
Query!
Assessment method [22]
0
0
FAQ scores 10 items & measures activities of daily living (paying bills/balancing checkbook, assembling tax records, shopping alone for clothes or groceries, playing game of skill such as bridge or chess/working on a hobby, heating water & turning off stove, preparing balanced meal, keeping track of current events, paying attention & understanding television program, remembering appointments, driving or traveling out of neighborhood). Each item is rated as follows: 0=Normal, 1=Has difficulty but does by self, 2=Requires assistance, 3=Dependent, or 8=Not Applicable. The total score is the sum of all 10 items & ranges from 0 to 30. Higher score indicates more impairment. If any activity was missed, then the total score was missed. Activities rated as "Not Applicable" were not used in the computation of the total score. To account for "Not Applicable" activity, the total score was weighted as:Total Score=Total Score*30/(30 minus 3 times the number of activities marked"Not Applicable").
Query!
Timepoint [22]
0
0
Baseline (Day 1: before first dose in the core phase) up to Month 12 of the extension phase
Query!
Secondary outcome [23]
0
0
Extension Phase: Change From Core Phase Baseline up to Month 12 of the Extension Phase in ADAS-cog14 Score
Query!
Assessment method [23]
0
0
ADAS-cog14 is a psychometric instrument that evaluates 14-items (Immediate Word-recall [0 to 10], Commands [0-5], Constructional Praxis [0-5], Delayed Word-recall [0-10], Naming Objects/Fingers [0-5], Ideational Praxis [0-5], Orientation[0-8], Word Recognition [0-12], Remembering Test Instructions [0-5], Comprehension[0-5], Word Finding Difficulty [0-5], Spoken Language Ability [0-5], Executive Function [0-5], and Number Cancellation [0-5] test). It is considered to be more sensitive for less impaired populations such as MCI/Prodromal and mild AD participants. The total score ranges from 0 to 90. Higher score indicates more impairment.
Query!
Timepoint [23]
0
0
Baseline (Day 1: before first dose in the core phase) up to Month 12 of the extension phase
Query!
Secondary outcome [24]
0
0
Extension Phase: Change From Core Phase Baseline up to Month 12 of the Extension Phase in ADAS-cog14 Word List (Immediate Recall and Delayed Recall) Score
Query!
Assessment method [24]
0
0
The ADAS-cog14 Word List is a summation of two items: "Immediate Word-recall" and "Delayed Word-recall". Immediate Word-recall test: Participants are asked to recall words and the number of "No" responses for each trial (total 3 trials) are summed. Subscore: sum of scores from 3 trials, divided by 3. Score ranges from 0 to 10. Delayed Word-recall: Participants used to recall words after a delay and the number of "No" responses are summed. Score ranges from 0 to 10. The Total Score ranges from 0 to 20. Higher score indicates more impairment.
Query!
Timepoint [24]
0
0
Baseline (Day 1: before first dose in the core phase) up to Month 12 of the extension phase
Query!
Secondary outcome [25]
0
0
Extension Phase: Time to Conversion to Dementia for Participants Who Were Not Clinically Staged as Having Dementia at the Core Phase Baseline up to Month 12 of the Extension Phase
Query!
Assessment method [25]
0
0
Time (in months) to conversion to dementia for participants who were not clinically staged as having dementia at the core phase baseline (that is time from randomization to conversion to dementia in clinical diagnosis).
Query!
Timepoint [25]
0
0
Baseline (Day 1: before first dose in the core phase) up to Month 12 of the extension phase
Query!
Eligibility
Key inclusion criteria
Core Study
- Mild cognitive impairment due to Alzheimer's disease (AD) or mild AD dementia
including
1. Mini Mental State Examination score equal to or greater than 24
2. Clinical Dementia Rating (CDR) global score of 0.5
3. CDR Memory Box score of 0.5 or greater
- Impaired episodic memory confirmed by a list learning task
- Positive biomarker for brain amyloid pathology as indicated by either amyloid positron
emission tomography or cerebrospinal fluid AD assessment or both
Extension Phase
• Participants who complete the Core Study
Query!
Minimum age
50
Years
Query!
Query!
Maximum age
85
Years
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
Key exclusion criteria
Core Study
- Females who are breastfeeding or pregnant at Screening or Baseline. Females of
child-bearing potential must use a highly effective method of contraception throughout
the entire study period and for 28 days after study drug discontinuation
- Any condition that may be contributing to cognitive impairment above and beyond that
caused by the participant's AD
- Participants with a history of seizures within 5 years of Screening
- History of transient ischemic attacks or stroke within 12 months of Screening
- Psychiatric diagnosis or symptoms (example, hallucinations, major depression,
delusions etc.)
- Suicidal ideation or any suicidal behavior within 6 months before Screening or has
been hospitalized or treated for suicidal behavior in the past 5 years
- Have any contraindications to magnetic resonance imaging (MRI) scanning or
1. Have lesions that could indicate a dementia diagnosis other than AD on brain MRI
2. Exhibit other significant pathological findings on brain MRI.
- Participants who have a history of moderate to severe hepatic impairment (example,
Child-Pugh Class B or C)
- Results of laboratory tests conducted during Screening that are outside the following
limits:
1. Absolute lymphocyte count below the lower limit of normal (LLN)
2. Thyroid stimulating hormone above normal range
3. Abnormally low Vitamin B12 levels
- Participants at increased risk of infection
- Have received any live vaccine/live attenuated vaccine in the 3 months before
randomization
- Any chronic inflammatory disease that is not adequately controlled or that requires
systemic immunosuppressive or immunomodulatory therapy
- Any other clinically significant abnormalities
- Severe visual or hearing impairment
- A prolonged corrected QT (QTc) interval (QT interval with Fridericia's correction
[QTcF] greater than 450 milliseconds [ms])
- Malignant neoplasms within 5 years of Screening
- Known or suspected history of drug or alcohol abuse
- Taking prohibited medications, which must be reviewed with the Investigator
- Have participated in a recent clinical study
Note: Other protocol-defined Inclusion/Exclusion Criteria may apply.
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Randomised controlled trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Blinded (masking used)
Query!
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Query!
Query!
Query!
Query!
Intervention assignment
Parallel
Query!
Other design features
Query!
Phase
Phase 3
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Terminated
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
20/10/2016
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
Query!
Actual
15/01/2020
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
2212
Query!
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Query!
Recruitment hospital [1]
0
0
Facility #1 - Darlinghurst
Query!
Recruitment hospital [2]
0
0
Facility #1 - Macquarie Park
Query!
Recruitment hospital [3]
0
0
Facility #1 - Tumbi Umbi
Query!
Recruitment hospital [4]
0
0
Facility #1 - Brisbane
Query!
Recruitment hospital [5]
0
0
Facility #1 - Caulfield
Query!
Recruitment hospital [6]
0
0
Facility #1 - Geelong
Query!
Recruitment hospital [7]
0
0
Facility #1 - Heidelberg
Query!
Recruitment hospital [8]
0
0
Facility #1 - Malvern
Query!
Recruitment hospital [9]
0
0
Facility #2 - Melbourne
Query!
Recruitment hospital [10]
0
0
Facility #1 - Parkville
Query!
Recruitment hospital [11]
0
0
Facility #1 - Nedlands
Query!
Recruitment hospital [12]
0
0
Facility #3 - Melbourne
Query!
Recruitment postcode(s) [1]
0
0
2010 - Darlinghurst
Query!
Recruitment postcode(s) [2]
0
0
2113 - Macquarie Park
Query!
Recruitment postcode(s) [3]
0
0
2261 - Tumbi Umbi
Query!
Recruitment postcode(s) [4]
0
0
4032 - Brisbane
Query!
Recruitment postcode(s) [5]
0
0
3162 - Caulfield
Query!
Recruitment postcode(s) [6]
0
0
3220 - Geelong
Query!
Recruitment postcode(s) [7]
0
0
3084 - Heidelberg
Query!
Recruitment postcode(s) [8]
0
0
3144 - Malvern
Query!
Recruitment postcode(s) [9]
0
0
- Melbourne
Query!
Recruitment postcode(s) [10]
0
0
3050 - Parkville
Query!
Recruitment postcode(s) [11]
0
0
6009 - Nedlands
Query!
Recruitment postcode(s) [12]
0
0
3146 - Melbourne
Query!
Recruitment outside Australia
Country [1]
0
0
United States of America
Query!
State/province [1]
0
0
Arizona
Query!
Country [2]
0
0
United States of America
Query!
State/province [2]
0
0
California
Query!
Country [3]
0
0
United States of America
Query!
State/province [3]
0
0
Colorado
Query!
Country [4]
0
0
United States of America
Query!
State/province [4]
0
0
Florida
Query!
Country [5]
0
0
United States of America
Query!
State/province [5]
0
0
Georgia
Query!
Country [6]
0
0
United States of America
Query!
State/province [6]
0
0
Idaho
Query!
Country [7]
0
0
United States of America
Query!
State/province [7]
0
0
Illinois
Query!
Country [8]
0
0
United States of America
Query!
State/province [8]
0
0
Kansas
Query!
Country [9]
0
0
United States of America
Query!
State/province [9]
0
0
Massachusetts
Query!
Country [10]
0
0
United States of America
Query!
State/province [10]
0
0
Michigan
Query!
Country [11]
0
0
United States of America
Query!
State/province [11]
0
0
Missouri
Query!
Country [12]
0
0
United States of America
Query!
State/province [12]
0
0
New Jersey
Query!
Country [13]
0
0
United States of America
Query!
State/province [13]
0
0
New York
Query!
Country [14]
0
0
United States of America
Query!
State/province [14]
0
0
Ohio
Query!
Country [15]
0
0
United States of America
Query!
State/province [15]
0
0
Oklahoma
Query!
Country [16]
0
0
United States of America
Query!
State/province [16]
0
0
Oregon
Query!
Country [17]
0
0
United States of America
Query!
State/province [17]
0
0
Pennsylvania
Query!
Country [18]
0
0
United States of America
Query!
State/province [18]
0
0
Rhode Island
Query!
Country [19]
0
0
United States of America
Query!
State/province [19]
0
0
South Carolina
Query!
Country [20]
0
0
United States of America
Query!
State/province [20]
0
0
Tennessee
Query!
Country [21]
0
0
United States of America
Query!
State/province [21]
0
0
Texas
Query!
Country [22]
0
0
United States of America
Query!
State/province [22]
0
0
Utah
Query!
Country [23]
0
0
United States of America
Query!
State/province [23]
0
0
Vermont
Query!
Country [24]
0
0
United States of America
Query!
State/province [24]
0
0
Virginia
Query!
Country [25]
0
0
United States of America
Query!
State/province [25]
0
0
Wisconsin
Query!
Country [26]
0
0
Argentina
Query!
State/province [26]
0
0
Buenos Aires
Query!
Country [27]
0
0
Argentina
Query!
State/province [27]
0
0
Capital
Query!
Country [28]
0
0
Argentina
Query!
State/province [28]
0
0
Santa Fe
Query!
Country [29]
0
0
Argentina
Query!
State/province [29]
0
0
Caba
Query!
Country [30]
0
0
Argentina
Query!
State/province [30]
0
0
Cordoba
Query!
Country [31]
0
0
Austria
Query!
State/province [31]
0
0
Vienna
Query!
Country [32]
0
0
Bulgaria
Query!
State/province [32]
0
0
Pleven
Query!
Country [33]
0
0
Bulgaria
Query!
State/province [33]
0
0
Plovdiv
Query!
Country [34]
0
0
Bulgaria
Query!
State/province [34]
0
0
Ruse
Query!
Country [35]
0
0
Bulgaria
Query!
State/province [35]
0
0
Sofia
Query!
Country [36]
0
0
Canada
Query!
State/province [36]
0
0
British Columbia
Query!
Country [37]
0
0
Canada
Query!
State/province [37]
0
0
Nova Scotia
Query!
Country [38]
0
0
Canada
Query!
State/province [38]
0
0
Ontario
Query!
Country [39]
0
0
Canada
Query!
State/province [39]
0
0
Quebec
Query!
Country [40]
0
0
Czechia
Query!
State/province [40]
0
0
Hradec Kralove
Query!
Country [41]
0
0
Czechia
Query!
State/province [41]
0
0
Kladno
Query!
Country [42]
0
0
Czechia
Query!
State/province [42]
0
0
Olomouc
Query!
Country [43]
0
0
Czechia
Query!
State/province [43]
0
0
Praha 10
Query!
Country [44]
0
0
France
Query!
State/province [44]
0
0
Herault
Query!
Country [45]
0
0
France
Query!
State/province [45]
0
0
Bordeaux
Query!
Country [46]
0
0
France
Query!
State/province [46]
0
0
Bron Cedex
Query!
Country [47]
0
0
France
Query!
State/province [47]
0
0
Marseille Cedex 05
Query!
Country [48]
0
0
France
Query!
State/province [48]
0
0
Nantes
Query!
Country [49]
0
0
France
Query!
State/province [49]
0
0
Paris
Query!
Country [50]
0
0
France
Query!
State/province [50]
0
0
Rouen
Query!
Country [51]
0
0
France
Query!
State/province [51]
0
0
Toulouse
Query!
Country [52]
0
0
Germany
Query!
State/province [52]
0
0
Bayern
Query!
Country [53]
0
0
Germany
Query!
State/province [53]
0
0
Brandenburg
Query!
Country [54]
0
0
Germany
Query!
State/province [54]
0
0
Hessen
Query!
Country [55]
0
0
Germany
Query!
State/province [55]
0
0
Saxony
Query!
Country [56]
0
0
Germany
Query!
State/province [56]
0
0
Berlin
Query!
Country [57]
0
0
Germany
Query!
State/province [57]
0
0
Gera
Query!
Country [58]
0
0
Germany
Query!
State/province [58]
0
0
Homburg/Saar
Query!
Country [59]
0
0
Germany
Query!
State/province [59]
0
0
Schwerin
Query!
Country [60]
0
0
Greece
Query!
State/province [60]
0
0
Athens
Query!
Country [61]
0
0
Japan
Query!
State/province [61]
0
0
Aichi
Query!
Country [62]
0
0
Japan
Query!
State/province [62]
0
0
Fukui
Query!
Country [63]
0
0
Japan
Query!
State/province [63]
0
0
Fukuoka
Query!
Country [64]
0
0
Japan
Query!
State/province [64]
0
0
Gunma
Query!
Country [65]
0
0
Japan
Query!
State/province [65]
0
0
Hiroshima
Query!
Country [66]
0
0
Japan
Query!
State/province [66]
0
0
Hyogo
Query!
Country [67]
0
0
Japan
Query!
State/province [67]
0
0
Kagawa
Query!
Country [68]
0
0
Japan
Query!
State/province [68]
0
0
Kanagawa
Query!
Country [69]
0
0
Japan
Query!
State/province [69]
0
0
Kyoto
Query!
Country [70]
0
0
Japan
Query!
State/province [70]
0
0
Miyazaki
Query!
Country [71]
0
0
Japan
Query!
State/province [71]
0
0
Okayama-ken
Query!
Country [72]
0
0
Japan
Query!
State/province [72]
0
0
Okayama
Query!
Country [73]
0
0
Japan
Query!
State/province [73]
0
0
Osaka
Query!
Country [74]
0
0
Japan
Query!
State/province [74]
0
0
Saga
Query!
Country [75]
0
0
Japan
Query!
State/province [75]
0
0
Shiga
Query!
Country [76]
0
0
Japan
Query!
State/province [76]
0
0
Tokushima
Query!
Country [77]
0
0
Japan
Query!
State/province [77]
0
0
Tokyo
Query!
Country [78]
0
0
Japan
Query!
State/province [78]
0
0
Yamaguchi
Query!
Country [79]
0
0
Japan
Query!
State/province [79]
0
0
Kumamoto
Query!
Country [80]
0
0
Korea, Republic of
Query!
State/province [80]
0
0
Gyeonggi-do
Query!
Country [81]
0
0
Korea, Republic of
Query!
State/province [81]
0
0
Gyeonggi
Query!
Country [82]
0
0
Korea, Republic of
Query!
State/province [82]
0
0
Busan
Query!
Country [83]
0
0
Korea, Republic of
Query!
State/province [83]
0
0
Incheon
Query!
Country [84]
0
0
Korea, Republic of
Query!
State/province [84]
0
0
Seoul
Query!
Country [85]
0
0
Poland
Query!
State/province [85]
0
0
Katowice
Query!
Country [86]
0
0
Poland
Query!
State/province [86]
0
0
Kielce
Query!
Country [87]
0
0
Poland
Query!
State/province [87]
0
0
Krakow
Query!
Country [88]
0
0
Poland
Query!
State/province [88]
0
0
Poznari
Query!
Country [89]
0
0
Poland
Query!
State/province [89]
0
0
Poznan
Query!
Country [90]
0
0
Poland
Query!
State/province [90]
0
0
Siemianowice Slaskie
Query!
Country [91]
0
0
Poland
Query!
State/province [91]
0
0
Warszawa
Query!
Country [92]
0
0
Portugal
Query!
State/province [92]
0
0
Guimarães
Query!
Country [93]
0
0
Russian Federation
Query!
State/province [93]
0
0
Moscow
Query!
Country [94]
0
0
Slovakia
Query!
State/province [94]
0
0
Bratislava
Query!
Country [95]
0
0
Spain
Query!
State/province [95]
0
0
Alicante
Query!
Country [96]
0
0
Spain
Query!
State/province [96]
0
0
Barcelona
Query!
Country [97]
0
0
Spain
Query!
State/province [97]
0
0
Bizkaia
Query!
Country [98]
0
0
Spain
Query!
State/province [98]
0
0
Gipuzkoa
Query!
Country [99]
0
0
Spain
Query!
State/province [99]
0
0
Illes Balears
Query!
Country [100]
0
0
Spain
Query!
State/province [100]
0
0
Murcia
Query!
Country [101]
0
0
Spain
Query!
State/province [101]
0
0
Madrid
Query!
Country [102]
0
0
Spain
Query!
State/province [102]
0
0
Valencia
Query!
Country [103]
0
0
United Kingdom
Query!
State/province [103]
0
0
Cambridgeshire
Query!
Country [104]
0
0
United Kingdom
Query!
State/province [104]
0
0
Cheshire
Query!
Country [105]
0
0
United Kingdom
Query!
State/province [105]
0
0
Devon
Query!
Country [106]
0
0
United Kingdom
Query!
State/province [106]
0
0
Dorset
Query!
Country [107]
0
0
United Kingdom
Query!
State/province [107]
0
0
East Sussex
Query!
Country [108]
0
0
United Kingdom
Query!
State/province [108]
0
0
Greater Manchester
Query!
Country [109]
0
0
United Kingdom
Query!
State/province [109]
0
0
Hampshire
Query!
Country [110]
0
0
United Kingdom
Query!
State/province [110]
0
0
Lanarkshire
Query!
Country [111]
0
0
United Kingdom
Query!
State/province [111]
0
0
Lancashire
Query!
Country [112]
0
0
United Kingdom
Query!
State/province [112]
0
0
Middlesex
Query!
Country [113]
0
0
United Kingdom
Query!
State/province [113]
0
0
North East Somerset
Query!
Country [114]
0
0
United Kingdom
Query!
State/province [114]
0
0
Oxfordshire
Query!
Country [115]
0
0
United Kingdom
Query!
State/province [115]
0
0
Scotland
Query!
Country [116]
0
0
United Kingdom
Query!
State/province [116]
0
0
South Yorkshire
Query!
Country [117]
0
0
United Kingdom
Query!
State/province [117]
0
0
Surrey
Query!
Country [118]
0
0
United Kingdom
Query!
State/province [118]
0
0
West Midlands
Query!
Country [119]
0
0
United Kingdom
Query!
State/province [119]
0
0
Wilts
Query!
Country [120]
0
0
United Kingdom
Query!
State/province [120]
0
0
Glasgow
Query!
Country [121]
0
0
United Kingdom
Query!
State/province [121]
0
0
Guildford
Query!
Country [122]
0
0
United Kingdom
Query!
State/province [122]
0
0
London
Query!
Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Query!
Name
Eisai Co., Ltd.
Query!
Address
Query!
Country
Query!
Other collaborator category [1]
0
0
Commercial sector/Industry
Query!
Name [1]
0
0
Biogen
Query!
Address [1]
0
0
Query!
Country [1]
0
0
Query!
Ethics approval
Ethics application status
Query!
Summary
Brief summary
The name of this trial is MissionAD1. This phase 3 study consists of a Core and Open Label
Extension (OLE) Phase in participants with Early Alzheimer's Disease (EAD), and will be
conducted to evaluate the efficacy and safety of E2609. The Core is a 24-month treatment,
multicenter, double blind, placebo controlled parallel group study. The OLE is a 24-month
treatment, one group study. The data for the studies E2609-G000-301 (NCT02956486, MissionAD1)
and E2609-G000-302 (NCT03036280, MissionAD2) will be pooled.
Query!
Trial website
https://clinicaltrials.gov/ct2/show/NCT02956486
Query!
Trial related presentations / publications
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT02956486
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