Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03036280




Registration number
NCT03036280
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
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
Secondary ID [1] 0 0
2016-003928-23
Secondary ID [2] 0 0
E2609-G000-301
Universal Trial Number (UTN)
Trial acronym
MissionAD1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alzheimer's Disease 0 0
Condition category
Condition code
Neurological 0 0 0 0
Alzheimer's disease
Neurological 0 0 0 0
Dementias

Intervention/exposure
Study type
Interventional
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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Core Phase: Change From Baseline up to Month 24 in the Clinical Dementia Rating-sum of Boxes (CDR-SB) Score
Assessment method [1] 0 0
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.
Timepoint [1] 0 0
Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase
Primary outcome [2] 0 0
Extension Phase: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
Assessment method [2] 0 0
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.
Timepoint [2] 0 0
From first dose of study drug up to approximately 6 months (including 1 month follow up) for the extension phase
Secondary outcome [1] 0 0
Core Phase: Change From Baseline up to Month 24 in Alzheimer's Disease Composite Score (ADCOMS)
Assessment method [1] 0 0
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.
Timepoint [1] 0 0
Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase
Secondary outcome [2] 0 0
Core Phase: Change From Baseline up to Month 24 in Amyloid Positron Emission Tomography (PET) Standardized Uptake Value Ratio (SUVR)
Assessment method [2] 0 0
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.
Timepoint [2] 0 0
Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase
Secondary outcome [3] 0 0
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
Assessment method [3] 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. 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.
Timepoint [3] 0 0
Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase
Secondary outcome [4] 0 0
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
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.
Timepoint [4] 0 0
Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase
Secondary outcome [5] 0 0
Core Phase: Change Per Year (Mean Slope) in CDR-SB Score up to Month 24
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.
Timepoint [5] 0 0
Up to Month 24 of the core phase
Secondary outcome [6] 0 0
Core Phase: Time to Worsening of CDR Score up to Month 24
Assessment method [6] 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 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.
Timepoint [6] 0 0
Up to Month 24 of the core phase
Secondary outcome [7] 0 0
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
Assessment method [7] 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).
Timepoint [7] 0 0
Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase
Secondary outcome [8] 0 0
Core Phase: Change From Baseline up to Month 24 in the Alzheimer's Disease Assessment Scale-cognition14 (ADAS-Cog14) Score
Assessment method [8] 0 0
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.
Timepoint [8] 0 0
Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase
Secondary outcome [9] 0 0
Core Phase: Change From Baseline up to Month 24 in the MMSE Score
Assessment method [9] 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.
Timepoint [9] 0 0
Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase
Secondary outcome [10] 0 0
Core Phase: Change From Baseline up to Month 24 in the Functional Assessment Questionnaire (FAQ) Score
Assessment method [10] 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").
Timepoint [10] 0 0
Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase
Secondary outcome [11] 0 0
Core Phase: Change From Baseline up to Month 24 in the ADAS-cog14 Word List (Immediate Recall and Delayed Recall) Score
Assessment method [11] 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.
Timepoint [11] 0 0
Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase
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
Assessment method [12] 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.
Timepoint [12] 0 0
Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase
Secondary outcome [13] 0 0
Core Phase: Change From Last Dose in the CDR-SB Score
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.
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)
Secondary outcome [14] 0 0
Core Phase: Change From Last Dose in the ADCOMS
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.
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)
Secondary outcome [15] 0 0
Core Phase: Change From Last Dose in the ADAS-cog11 Score
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.
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)
Secondary outcome [16] 0 0
Core Phase: Change From Last Dose in the ADAS-cog14 Score
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.
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)
Secondary outcome [17] 0 0
Core Phase: Change From Last Dose in the MMSE Score
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.
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)
Secondary outcome [18] 0 0
Core Phase: Change From Last Dose in the ADAS-cog14 Word List (Immediate Recall and Delayed Recall) Score
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.
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)
Secondary outcome [19] 0 0
Extension Phase: Change From Core Phase Baseline up to Month 12 of the Extension Phase in CDR-SB Score
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.
Timepoint [19] 0 0
Baseline (Day 1: before first dose in the core phase) up to Month 12 of the extension phase
Secondary outcome [20] 0 0
Extension Phase: Change From Core Phase Baseline up to Month 12 of the Extension Phase in ADCOMS
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.
Timepoint [20] 0 0
Baseline (Day 1: before first dose in the core phase) up to Month 12 of the extension phase
Secondary outcome [21] 0 0
Extension Phase: Change From Core Phase Baseline up to Month 12 of the Extension Phase in MMSE Score
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.
Timepoint [21] 0 0
Baseline (Day 1: before first dose in the core phase) up to Month 12 of the extension phase
Secondary outcome [22] 0 0
Extension Phase: Change From Core Phase Baseline up to Month 12 of the Extension Phase in FAQ Score
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").
Timepoint [22] 0 0
Baseline (Day 1: before first dose in the core phase) up to Month 12 of the extension phase
Secondary outcome [23] 0 0
Extension Phase: Change From Core Phase Baseline up to Month 12 of the Extension Phase in ADAS-cog14 Score
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.
Timepoint [23] 0 0
Baseline (Day 1: before first dose in the core phase) up to Month 12 of the extension phase
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
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.
Timepoint [24] 0 0
Baseline (Day 1: before first dose in the core phase) up to Month 12 of the extension phase
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
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).
Timepoint [25] 0 0
Baseline (Day 1: before first dose in the core phase) up to Month 12 of the extension phase

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
Minimum age
50 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
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
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
20/10/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
15/01/2020
Sample size
Target
Accrual to date
Final
2212
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Facility #1 - Darlinghurst
Recruitment hospital [2] 0 0
Facility #1 - Macquarie Park
Recruitment hospital [3] 0 0
Facility #1 - Tumbi Umbi
Recruitment hospital [4] 0 0
Facility #1 - Brisbane
Recruitment hospital [5] 0 0
Facility #1 - Caulfield
Recruitment hospital [6] 0 0
Facility #1 - Geelong
Recruitment hospital [7] 0 0
Facility #1 - Heidelberg
Recruitment hospital [8] 0 0
Facility #1 - Malvern
Recruitment hospital [9] 0 0
Facility #2 - Melbourne
Recruitment hospital [10] 0 0
Facility #1 - Parkville
Recruitment hospital [11] 0 0
Facility #1 - Nedlands
Recruitment hospital [12] 0 0
Facility #3 - Melbourne
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2113 - Macquarie Park
Recruitment postcode(s) [3] 0 0
2261 - Tumbi Umbi
Recruitment postcode(s) [4] 0 0
4032 - Brisbane
Recruitment postcode(s) [5] 0 0
3162 - Caulfield
Recruitment postcode(s) [6] 0 0
3220 - Geelong
Recruitment postcode(s) [7] 0 0
3084 - Heidelberg
Recruitment postcode(s) [8] 0 0
3144 - Malvern
Recruitment postcode(s) [9] 0 0
- Melbourne
Recruitment postcode(s) [10] 0 0
3050 - Parkville
Recruitment postcode(s) [11] 0 0
6009 - Nedlands
Recruitment postcode(s) [12] 0 0
3146 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Idaho
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Kansas
Country [9] 0 0
United States of America
State/province [9] 0 0
Massachusetts
Country [10] 0 0
United States of America
State/province [10] 0 0
Michigan
Country [11] 0 0
United States of America
State/province [11] 0 0
Missouri
Country [12] 0 0
United States of America
State/province [12] 0 0
New Jersey
Country [13] 0 0
United States of America
State/province [13] 0 0
New York
Country [14] 0 0
United States of America
State/province [14] 0 0
Ohio
Country [15] 0 0
United States of America
State/province [15] 0 0
Oklahoma
Country [16] 0 0
United States of America
State/province [16] 0 0
Oregon
Country [17] 0 0
United States of America
State/province [17] 0 0
Pennsylvania
Country [18] 0 0
United States of America
State/province [18] 0 0
Rhode Island
Country [19] 0 0
United States of America
State/province [19] 0 0
South Carolina
Country [20] 0 0
United States of America
State/province [20] 0 0
Tennessee
Country [21] 0 0
United States of America
State/province [21] 0 0
Texas
Country [22] 0 0
United States of America
State/province [22] 0 0
Utah
Country [23] 0 0
United States of America
State/province [23] 0 0
Vermont
Country [24] 0 0
United States of America
State/province [24] 0 0
Virginia
Country [25] 0 0
United States of America
State/province [25] 0 0
Wisconsin
Country [26] 0 0
Argentina
State/province [26] 0 0
Buenos Aires
Country [27] 0 0
Argentina
State/province [27] 0 0
Capital
Country [28] 0 0
Argentina
State/province [28] 0 0
Santa Fe
Country [29] 0 0
Argentina
State/province [29] 0 0
Caba
Country [30] 0 0
Argentina
State/province [30] 0 0
Cordoba
Country [31] 0 0
Austria
State/province [31] 0 0
Vienna
Country [32] 0 0
Bulgaria
State/province [32] 0 0
Pleven
Country [33] 0 0
Bulgaria
State/province [33] 0 0
Plovdiv
Country [34] 0 0
Bulgaria
State/province [34] 0 0
Ruse
Country [35] 0 0
Bulgaria
State/province [35] 0 0
Sofia
Country [36] 0 0
Canada
State/province [36] 0 0
British Columbia
Country [37] 0 0
Canada
State/province [37] 0 0
Nova Scotia
Country [38] 0 0
Canada
State/province [38] 0 0
Ontario
Country [39] 0 0
Canada
State/province [39] 0 0
Quebec
Country [40] 0 0
Czechia
State/province [40] 0 0
Hradec Kralove
Country [41] 0 0
Czechia
State/province [41] 0 0
Kladno
Country [42] 0 0
Czechia
State/province [42] 0 0
Olomouc
Country [43] 0 0
Czechia
State/province [43] 0 0
Praha 10
Country [44] 0 0
France
State/province [44] 0 0
Herault
Country [45] 0 0
France
State/province [45] 0 0
Bordeaux
Country [46] 0 0
France
State/province [46] 0 0
Bron Cedex
Country [47] 0 0
France
State/province [47] 0 0
Marseille Cedex 05
Country [48] 0 0
France
State/province [48] 0 0
Nantes
Country [49] 0 0
France
State/province [49] 0 0
Paris
Country [50] 0 0
France
State/province [50] 0 0
Rouen
Country [51] 0 0
France
State/province [51] 0 0
Toulouse
Country [52] 0 0
Germany
State/province [52] 0 0
Bayern
Country [53] 0 0
Germany
State/province [53] 0 0
Brandenburg
Country [54] 0 0
Germany
State/province [54] 0 0
Hessen
Country [55] 0 0
Germany
State/province [55] 0 0
Saxony
Country [56] 0 0
Germany
State/province [56] 0 0
Berlin
Country [57] 0 0
Germany
State/province [57] 0 0
Gera
Country [58] 0 0
Germany
State/province [58] 0 0
Homburg/Saar
Country [59] 0 0
Germany
State/province [59] 0 0
Schwerin
Country [60] 0 0
Greece
State/province [60] 0 0
Athens
Country [61] 0 0
Japan
State/province [61] 0 0
Aichi
Country [62] 0 0
Japan
State/province [62] 0 0
Fukui
Country [63] 0 0
Japan
State/province [63] 0 0
Fukuoka
Country [64] 0 0
Japan
State/province [64] 0 0
Gunma
Country [65] 0 0
Japan
State/province [65] 0 0
Hiroshima
Country [66] 0 0
Japan
State/province [66] 0 0
Hyogo
Country [67] 0 0
Japan
State/province [67] 0 0
Kagawa
Country [68] 0 0
Japan
State/province [68] 0 0
Kanagawa
Country [69] 0 0
Japan
State/province [69] 0 0
Kyoto
Country [70] 0 0
Japan
State/province [70] 0 0
Miyazaki
Country [71] 0 0
Japan
State/province [71] 0 0
Okayama-ken
Country [72] 0 0
Japan
State/province [72] 0 0
Okayama
Country [73] 0 0
Japan
State/province [73] 0 0
Osaka
Country [74] 0 0
Japan
State/province [74] 0 0
Saga
Country [75] 0 0
Japan
State/province [75] 0 0
Shiga
Country [76] 0 0
Japan
State/province [76] 0 0
Tokushima
Country [77] 0 0
Japan
State/province [77] 0 0
Tokyo
Country [78] 0 0
Japan
State/province [78] 0 0
Yamaguchi
Country [79] 0 0
Japan
State/province [79] 0 0
Kumamoto
Country [80] 0 0
Korea, Republic of
State/province [80] 0 0
Gyeonggi-do
Country [81] 0 0
Korea, Republic of
State/province [81] 0 0
Gyeonggi
Country [82] 0 0
Korea, Republic of
State/province [82] 0 0
Busan
Country [83] 0 0
Korea, Republic of
State/province [83] 0 0
Incheon
Country [84] 0 0
Korea, Republic of
State/province [84] 0 0
Seoul
Country [85] 0 0
Poland
State/province [85] 0 0
Katowice
Country [86] 0 0
Poland
State/province [86] 0 0
Kielce
Country [87] 0 0
Poland
State/province [87] 0 0
Krakow
Country [88] 0 0
Poland
State/province [88] 0 0
Poznari
Country [89] 0 0
Poland
State/province [89] 0 0
Poznan
Country [90] 0 0
Poland
State/province [90] 0 0
Siemianowice Slaskie
Country [91] 0 0
Poland
State/province [91] 0 0
Warszawa
Country [92] 0 0
Portugal
State/province [92] 0 0
Guimarães
Country [93] 0 0
Russian Federation
State/province [93] 0 0
Moscow
Country [94] 0 0
Slovakia
State/province [94] 0 0
Bratislava
Country [95] 0 0
Spain
State/province [95] 0 0
Alicante
Country [96] 0 0
Spain
State/province [96] 0 0
Barcelona
Country [97] 0 0
Spain
State/province [97] 0 0
Bizkaia
Country [98] 0 0
Spain
State/province [98] 0 0
Gipuzkoa
Country [99] 0 0
Spain
State/province [99] 0 0
Illes Balears
Country [100] 0 0
Spain
State/province [100] 0 0
Murcia
Country [101] 0 0
Spain
State/province [101] 0 0
Madrid
Country [102] 0 0
Spain
State/province [102] 0 0
Valencia
Country [103] 0 0
United Kingdom
State/province [103] 0 0
Cambridgeshire
Country [104] 0 0
United Kingdom
State/province [104] 0 0
Cheshire
Country [105] 0 0
United Kingdom
State/province [105] 0 0
Devon
Country [106] 0 0
United Kingdom
State/province [106] 0 0
Dorset
Country [107] 0 0
United Kingdom
State/province [107] 0 0
East Sussex
Country [108] 0 0
United Kingdom
State/province [108] 0 0
Greater Manchester
Country [109] 0 0
United Kingdom
State/province [109] 0 0
Hampshire
Country [110] 0 0
United Kingdom
State/province [110] 0 0
Lanarkshire
Country [111] 0 0
United Kingdom
State/province [111] 0 0
Lancashire
Country [112] 0 0
United Kingdom
State/province [112] 0 0
Middlesex
Country [113] 0 0
United Kingdom
State/province [113] 0 0
North East Somerset
Country [114] 0 0
United Kingdom
State/province [114] 0 0
Oxfordshire
Country [115] 0 0
United Kingdom
State/province [115] 0 0
Scotland
Country [116] 0 0
United Kingdom
State/province [116] 0 0
South Yorkshire
Country [117] 0 0
United Kingdom
State/province [117] 0 0
Surrey
Country [118] 0 0
United Kingdom
State/province [118] 0 0
West Midlands
Country [119] 0 0
United Kingdom
State/province [119] 0 0
Wilts
Country [120] 0 0
United Kingdom
State/province [120] 0 0
Glasgow
Country [121] 0 0
United Kingdom
State/province [121] 0 0
Guildford
Country [122] 0 0
United Kingdom
State/province [122] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Eisai Co., Ltd.
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Biogen
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT03036280