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TerminatedNCT02956486MissionAD1Updated Feb 3, 2021Results posted

A 24-Month Study to Evaluate the Efficacy and Safety of Elenbecestat (E2609) in Participants With Early Alzheimer's Disease

A Phase 3 interventional study of Elenbecestat and Placebo in Alzheimer's Disease, sponsored by Eisai Co., Ltd.. Terminated at 258 sites in 18 countries. Open to participants aged 50 Years to 85 Years. Per ClinicalTrials.gov, last updated 2021-02-03.

Sponsored by Eisai Co., Ltd. · Phase 3, Interventional, and Treatment

Why this study was terminated
Due to an unfavorable risk-benefit ratio including no evidence of potential efficacy, and the adverse event profile of E2609 being worse than placebo.
Phase
Phase 3
Study type
Interventional
Enrollment
2,212
Allocation
Randomized
Ages
50 Years to 85 Years
Sex
All
01

Study 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.

02

Conditions studied

  • Alzheimer's Disease

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Keywords

  • Elenbecestat
  • E2609
  • Alzheimer's Disease
  • Early Alzheimer's Disease
  • Prodromal Alzheimer's Disease
  • Dementia
  • Dementia, Alzheimer's type
  • Mild Cognitive Impairment
  • MissionAD1
03

In context

Alzheimer Disease

3,678 studies on the registry are indexed under Alzheimer Disease; 872 are open to participants now.

This study's enrollment of 2,212 is above the median of 70 across 2,808 interventional studies indexed under Alzheimer Disease.

Browse Alzheimer Disease studies →

Lead sponsor

Eisai Co., Ltd. is the lead sponsor of 149 studies on the registry; 5 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
50 Years to 85 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

Exclusion criteria

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.

05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
2,212 participants (actual)

Study arms

  • 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.

    Drug: Elenbecestat

  • 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.

    Drug: Placebo

  • 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.

    Drug: Elenbecestat

Interventions

  • DrugElenbecestat

    Oral tablet.

    Also known as: E2609

  • DrugPlacebo

    Oral tablet.

06

What researchers measure

Primary outcomes

  1. Core Phase: Change From Baseline up to Month 24 in the Clinical Dementia Rating-sum of Boxes (CDR-SB) Score

    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.

    Time frame: Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase

  2. Extension Phase: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)

    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.

    Time frame: From first dose of study drug up to approximately 6 months (including 1 month follow up) for the extension phase

Secondary outcomes

  1. Core Phase: Change From Baseline up to Month 24 in Alzheimer's Disease Composite Score (ADCOMS)

    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.

    Time frame: Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase

  2. Core Phase: Change From Baseline up to Month 24 in Amyloid Positron Emission Tomography (PET) Standardized Uptake Value Ratio (SUVR)

    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.

    Time frame: Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase

  3. 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

    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.

    Time frame: Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase

  4. 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

    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.

    Time frame: Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase

  5. Core Phase: Change Per Year (Mean Slope) in CDR-SB Score up to Month 24

    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.

    Time frame: Up to Month 24 of the core phase

  6. Core Phase: Time to Worsening of CDR Score up to Month 24

    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.

    Time frame: Up to Month 24 of the core phase

  7. 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

    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).

    Time frame: Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase

  8. Core Phase: Change From Baseline up to Month 24 in the Alzheimer's Disease Assessment Scale-cognition14 (ADAS-Cog14) Score

    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.

    Time frame: Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase

  9. Core Phase: Change From Baseline up to Month 24 in the MMSE Score

    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.

    Time frame: Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase

  10. Core Phase: Change From Baseline up to Month 24 in the Functional Assessment Questionnaire (FAQ) Score

    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").

    Time frame: Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase

  11. Core Phase: Change From Baseline up to Month 24 in the ADAS-cog14 Word List (Immediate Recall and Delayed Recall) Score

    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.

    Time frame: Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase

  12. Core Phase: Change From Baseline up to Month 24 in the Alzheimer's Disease Assessment Scale-cognition11 (ADAS-Cog11) Score

    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.

    Time frame: Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase

  13. Core Phase: Change From Last Dose in the CDR-SB Score

    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.

    Time frame: From last dose in the core phase (up to Month 24) up to 3 months follow up (up to Month 27)

  14. Core Phase: Change From Last Dose in the ADCOMS

    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.

    Time frame: From last dose in the core phase (up to Month 24) up to 3 months follow-up (up to Month 27)

  15. Core Phase: Change From Last Dose in the ADAS-cog11 Score

    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.

    Time frame: From last dose in the core phase (up to Month 24) up to 3 months follow-up (up to Month 27)

  16. Core Phase: Change From Last Dose in the ADAS-cog14 Score

    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.

    Time frame: From last dose in the core phase (up to Month 24) up to 3 months follow-up (up to Month 27)

  17. Core Phase: Change From Last Dose in the MMSE Score

    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.

    Time frame: From last dose in the core phase (up to Month 24) up to 3 months follow-up (up to Month 27)

  18. Core Phase: Change From Last Dose in the ADAS-cog14 Word List (Immediate Recall and Delayed Recall) Score

    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.

    Time frame: From last dose in the core phase (up to Month 24) up to 3 months follow-up (up to Month 27)

  19. Extension Phase: Change From Core Phase Baseline up to Month 12 of the Extension Phase in CDR-SB Score

    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.

    Time frame: Baseline (Day 1: before first dose in the core phase) up to Month 12 of the extension phase

  20. Extension Phase: Change From Core Phase Baseline up to Month 12 of the Extension Phase in ADCOMS

    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.

    Time frame: Baseline (Day 1: before first dose in the core phase) up to Month 12 of the extension phase

  21. Extension Phase: Change From Core Phase Baseline up to Month 12 of the Extension Phase in MMSE Score

    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.

    Time frame: Baseline (Day 1: before first dose in the core phase) up to Month 12 of the extension phase

  22. Extension Phase: Change From Core Phase Baseline up to Month 12 of the Extension Phase in FAQ Score

    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").

    Time frame: Baseline (Day 1: before first dose in the core phase) up to Month 12 of the extension phase

  23. Extension Phase: Change From Core Phase Baseline up to Month 12 of the Extension Phase in ADAS-cog14 Score

    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.

    Time frame: Baseline (Day 1: before first dose in the core phase) up to Month 12 of the extension phase

  24. 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

    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.

    Time frame: Baseline (Day 1: before first dose in the core phase) up to Month 12 of the extension phase

  25. 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

    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).

    Time frame: Baseline (Day 1: before first dose in the core phase) up to Month 12 of the extension phase

07

Results

Posted Feb 3, 2021
Limitations and caveats
This study was terminated early due to an unfavorable risk-benefit ratio including no evidence of potential efficacy and the adverse event profile in participants with drug treatment was worse than that in participants who received placebo. The small sample size at the 24 month time point of the core phase limits the interpretability of the data.

Participant flow

Participants took part in the study at 426 investigative sites in China, Bulgaria, Croatia, Czech Republic, Greece, Hungary, Poland, Russia, Slovakia, Japan, Canada, Singapore, South Korea, Taiwan, Argentina, Chile, Mexico, Australia, Austria, Denmark, Finland, France, Germany, Italy, Portugal, South Africa, Spain, United Kingdom and the United States from 20 October 2016 to 15 January 2020.

Core Phase
Participant flow — Core Phase
MilestoneCore Phase: PlaceboCore Phase: Elenbecestat 50 mgExtension Phase: Elenbecestat 50 mg
Started110811040
Treated110811010
Safety analysis set (sas)110510990
Full analysis set (fas)108410620
Completed29320
Not completed107910720
Withdrew: Adverse event51880
Withdrew: Lost to follow-up860
Withdrew: Inadequate therapeutic effect450
Withdrew: Withdrawal by subject1011040
Withdrew: Study terminated by sponsor8888480
Withdrew: Other27180
Withdrew: Not treated030
Extension Phase
Participant flow — Extension Phase
MilestoneCore Phase: PlaceboCore Phase: Elenbecestat 50 mgExtension Phase: Elenbecestat 50 mg
Started0019
Treated0018
Safety analysis set (sas)0018
Completed000
Not completed0019
Withdrew: Adverse event002
Withdrew: Study terminated by sponsor0016
Withdrew: Not treated001

Outcome measures

PrimaryCore Phase: Change From Baseline up to Month 24 in the Clinical Dementia Rating-sum of Boxes (CDR-SB) Score

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.

Time frame:
Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase
Reported as:
Least squares mean · score on a scale
Core Phase: Change From Baseline up to Month 24 in the Clinical Dementia Rating-sum of Boxes (CDR-SB) Score
score on a scaleCore Phase: PlaceboCore Phase: Elenbecestat 50 mg
Core Phase: Change From Baseline up to Month 24 in the Clinical Dementia Rating-sum of Boxes (CDR-SB) Score2.17 ± 0.1421.99 ± 0.146
Statistical analysis
  • Core Phase: Placebo vs Core Phase: Elenbecestat 50 mg · MMRM · p = 0.385 · Least square (ls) mean difference: -0.17 · 95% CI -0.57 to 0.22
PrimaryExtension Phase: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)

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.

Time frame:
From first dose of study drug up to approximately 6 months (including 1 month follow up) for the extension phase
Reported as:
Count of participants · Participants
Extension Phase: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
ParticipantsExtension Phase: Elenbecestat 50 mg
Extension Phase: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)6
SecondaryCore Phase: Change From Baseline up to Month 24 in Alzheimer's Disease Composite Score (ADCOMS)

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.

Time frame:
Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase
Reported as:
Least squares mean · score on a scale
Core Phase: Change From Baseline up to Month 24 in Alzheimer's Disease Composite Score (ADCOMS)
score on a scaleCore Phase: PlaceboCore Phase: Elenbecestat 50 mg
Core Phase: Change From Baseline up to Month 24 in Alzheimer's Disease Composite Score (ADCOMS)0.24 ± 0.0140.23 ± 0.015
Statistical analysis
  • Core Phase: Placebo vs Core Phase: Elenbecestat 50 mg · MMRM · p = 0.345 · Ls mean difference: -0.02 · 95% CI -0.06 to 0.02
SecondaryCore Phase: Change From Baseline up to Month 24 in Amyloid Positron Emission Tomography (PET) Standardized Uptake Value Ratio (SUVR)

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.

Time frame:
Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase
Reported as:
Least squares mean · score on a scale
Core Phase: Change From Baseline up to Month 24 in Amyloid Positron Emission Tomography (PET) Standardized Uptake Value Ratio (SUVR)
score on a scaleCore Phase: PlaceboCore Phase: Elenbecestat 50 mg
Core Phase: Change From Baseline up to Month 24 in Amyloid Positron Emission Tomography (PET) Standardized Uptake Value Ratio (SUVR)7.81 ± 2.500-5.02 ± 2.046
Statistical analysis
  • Core Phase: Placebo vs Core Phase: Elenbecestat 50 mg · MMRM · p = <.001 · Ls mean difference: -12.83 · 95% CI -18.79 to -6.88
SecondaryCore 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

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.

Time frame:
Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase
Reported as:
Least squares mean · score on a scale
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
score on a scaleCore Phase: PlaceboCore Phase: Elenbecestat 50 mg
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 1.61.97 ± 0.1571.74 ± 0.169
Statistical analysis
  • Core Phase: Placebo vs Core Phase: Elenbecestat 50 mg · MMRM · p = 0.316 · Ls mean difference: -0.23 · 95% CI -0.67 to 0.22
SecondaryCore 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

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.

Time frame:
Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase
Reported as:
Least squares mean · score on a scale
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
score on a scaleCore Phase: PlaceboCore Phase: Elenbecestat 50 mg
Core Phase: Change From Baseline up to Month 24 in the ADCOMS for Participants Enriched by Baseline Amyloid PET SUVR Between 1.2 and 1.60.23 ± 0.0170.20 ± 0.018
Statistical analysis
  • Core Phase: Placebo vs Core Phase: Elenbecestat 50 mg · MMRM · p = 0.254 · Ls mean difference: -0.03 · 95% CI -0.07 to 0.02
SecondaryCore Phase: Change Per Year (Mean Slope) in CDR-SB Score up to Month 24

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.

Time frame:
Up to Month 24 of the core phase
Reported as:
Least squares mean · change in score per year
Core Phase: Change Per Year (Mean Slope) in CDR-SB Score up to Month 24
change in score per yearCore Phase: PlaceboCore Phase: Elenbecestat 50 mg
Core Phase: Change Per Year (Mean Slope) in CDR-SB Score up to Month 240.934 (0.838 to 1.030)0.926 (0.828 to 1.024)
Statistical analysis
  • Core Phase: Placebo vs Core Phase: Elenbecestat 50 mg · Linear mixed effects model · p = 0.9088 · Difference of mean slope: -0.008 · 95% CI -0.145 to 0.129
SecondaryCore Phase: Time to Worsening of CDR Score up to Month 24

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.

Time frame:
Up to Month 24 of the core phase
Reported as:
Median · months
Core Phase: Time to Worsening of CDR Score up to Month 24
monthsCore Phase: PlaceboCore Phase: Elenbecestat 50 mg
Core Phase: Time to Worsening of CDR Score up to Month 24NA (NA to NA)NA (24.07 to NA)
Statistical analysis
  • Core Phase: Placebo vs Core Phase: Elenbecestat 50 mg · Regression, Cox · p = 0.6155 · Hazard ratio (hr): 0.95 · 95% CI 0.77 to 1.16
SecondaryCore 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

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).

Time frame:
Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase
Reported as:
Median · months
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
monthsCore Phase: PlaceboCore Phase: Elenbecestat 50 mg
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 2423.05 (21.14 to 24.66)21.40 (20.45 to 24.43)
Statistical analysis
  • Core Phase: Placebo vs Core Phase: Elenbecestat 50 mg · Regression, Cox · p = 0.1281 · Hazard ratio (hr): 1.14 · 95% CI 0.96 to 1.35
SecondaryCore Phase: Change From Baseline up to Month 24 in the Alzheimer's Disease Assessment Scale-cognition14 (ADAS-Cog14) Score

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.

Time frame:
Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase
Reported as:
Least squares mean · score on a scale
Core Phase: Change From Baseline up to Month 24 in the Alzheimer's Disease Assessment Scale-cognition14 (ADAS-Cog14) Score
score on a scaleCore Phase: PlaceboCore Phase: Elenbecestat 50 mg
Core Phase: Change From Baseline up to Month 24 in the Alzheimer's Disease Assessment Scale-cognition14 (ADAS-Cog14) Score5.38 ± 0.4904.95 ± 0.520
Statistical analysis
  • Core Phase: Placebo vs Core Phase: Elenbecestat 50 mg · MMRM · p = 0.525 · Ls mean difference: -0.43 · 95% CI -1.75 to 0.90
SecondaryCore Phase: Change From Baseline up to Month 24 in the MMSE Score

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.

Time frame:
Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase
Reported as:
Least squares mean · score on a scale
Core Phase: Change From Baseline up to Month 24 in the MMSE Score
score on a scaleCore Phase: PlaceboCore Phase: Elenbecestat 50 mg
Core Phase: Change From Baseline up to Month 24 in the MMSE Score-2.87 ± 0.234-2.87 ± 0.241
Statistical analysis
  • Core Phase: Placebo vs Core Phase: Elenbecestat 50 mg · MMRM · p = 0.977 · Ls mean difference: -0.01 · 95% CI -0.64 to 0.62
SecondaryCore Phase: Change From Baseline up to Month 24 in the Functional Assessment Questionnaire (FAQ) Score

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").

Time frame:
Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase
Reported as:
Least squares mean · score on a scale
Core Phase: Change From Baseline up to Month 24 in the Functional Assessment Questionnaire (FAQ) Score
score on a scaleCore Phase: PlaceboCore Phase: Elenbecestat 50 mg
Core Phase: Change From Baseline up to Month 24 in the Functional Assessment Questionnaire (FAQ) Score5.20 ± 0.4485.32 ± 0.459
Statistical analysis
  • Core Phase: Placebo vs Core Phase: Elenbecestat 50 mg · MMRM · p = 0.854 · Ls mean difference: 0.11 · 95% CI -1.09 to 1.32
SecondaryCore Phase: Change From Baseline up to Month 24 in the ADAS-cog14 Word List (Immediate Recall and Delayed Recall) Score

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.

Time frame:
Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase
Reported as:
Least squares mean · score on a scale
Core Phase: Change From Baseline up to Month 24 in the ADAS-cog14 Word List (Immediate Recall and Delayed Recall) Score
score on a scaleCore Phase: PlaceboCore Phase: Elenbecestat 50 mg
Core Phase: Change From Baseline up to Month 24 in the ADAS-cog14 Word List (Immediate Recall and Delayed Recall) Score1.63 ± 0.1951.36 ± 0.207
Statistical analysis
  • Core Phase: Placebo vs Core Phase: Elenbecestat 50 mg · MMRM · p = 0.314 · Ls mean difference: -0.27 · 95% CI -0.79 to 0.26
SecondaryCore Phase: Change From Baseline up to Month 24 in the Alzheimer's Disease Assessment Scale-cognition11 (ADAS-Cog11) Score

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.

Time frame:
Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase
Reported as:
Least squares mean · score on a scale
Core Phase: Change From Baseline up to Month 24 in the Alzheimer's Disease Assessment Scale-cognition11 (ADAS-Cog11) Score
score on a scaleCore Phase: PlaceboCore Phase: Elenbecestat 50 mg
Core Phase: Change From Baseline up to Month 24 in the Alzheimer's Disease Assessment Scale-cognition11 (ADAS-Cog11) Score4.11 ± 0.3704.18 ± 0.391
Statistical analysis
  • Core Phase: Placebo vs Core Phase: Elenbecestat 50 mg · MMRM · p = 0.895 · Ls mean difference: 0.07 · 95% CI -0.93 to 1.07
SecondaryCore Phase: Change From Last Dose in the CDR-SB Score

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.

Time frame:
From last dose in the core phase (up to Month 24) up to 3 months follow up (up to Month 27)
Reported as:
Least squares mean · score on a scale
Core Phase: Change From Last Dose in the CDR-SB Score
score on a scaleCore Phase: PlaceboCore Phase: Elenbecestat 50 mg
Core Phase: Change From Last Dose in the CDR-SB Score0.40 ± 0.0450.44 ± 0.046
Statistical analysis
  • Core Phase: Placebo vs Core Phase: Elenbecestat 50 mg · MMRM · p = 0.542 · Ls mean difference: 0.04 · 95% CI -0.09 to 0.17
SecondaryCore Phase: Change From Last Dose in the ADCOMS

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.

Time frame:
From last dose in the core phase (up to Month 24) up to 3 months follow-up (up to Month 27)
Reported as:
Least squares mean · score on a scale
Core Phase: Change From Last Dose in the ADCOMS
score on a scaleCore Phase: PlaceboCore Phase: Elenbecestat 50 mg
Core Phase: Change From Last Dose in the ADCOMS0.06 ± 0.0050.06 ± 0.005
Statistical analysis
  • Core Phase: Placebo vs Core Phase: Elenbecestat 50 mg · MMRM · p = 0.380 · Ls mean difference: -0.01 · 95% CI -0.02 to 0.01
SecondaryCore Phase: Change From Last Dose in the ADAS-cog11 Score

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.

Time frame:
From last dose in the core phase (up to Month 24) up to 3 months follow-up (up to Month 27)
Reported as:
Least squares mean · score on a scale
Core Phase: Change From Last Dose in the ADAS-cog11 Score
score on a scaleCore Phase: PlaceboCore Phase: Elenbecestat 50 mg
Core Phase: Change From Last Dose in the ADAS-cog11 Score0.95 ± 0.1500.56 ± 0.153
Statistical analysis
  • Core Phase: Placebo vs Core Phase: Elenbecestat 50 mg · MMRM · p = 0.063 · Ls mean difference: -0.40 · 95% CI -0.82 to 0.02
SecondaryCore Phase: Change From Last Dose in the ADAS-cog14 Score

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.

Time frame:
From last dose in the core phase (up to Month 24) up to 3 months follow-up (up to Month 27)
Reported as:
Least squares mean · score on a scale
Core Phase: Change From Last Dose in the ADAS-cog14 Score
score on a scaleCore Phase: PlaceboCore Phase: Elenbecestat 50 mg
Core Phase: Change From Last Dose in the ADAS-cog14 Score0.96 ± 0.1960.40 ± 0.201
Statistical analysis
  • Core Phase: Placebo vs Core Phase: Elenbecestat 50 mg · MMRM · p = 0.045 · Ls mean difference: -0.56 · 95% CI -1.11 to -0.01
SecondaryCore Phase: Change From Last Dose in the MMSE Score

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.

Time frame:
From last dose in the core phase (up to Month 24) up to 3 months follow-up (up to Month 27)
Reported as:
Least squares mean · score on a scale
Core Phase: Change From Last Dose in the MMSE Score
score on a scaleCore Phase: PlaceboCore Phase: Elenbecestat 50 mg
Core Phase: Change From Last Dose in the MMSE Score-0.22 ± 0.101-0.26 ± 0.102
Statistical analysis
  • Core Phase: Placebo vs Core Phase: Elenbecestat 50 mg · MMRM · p = 0.799 · Ls mean difference: -0.04 · 95% CI -0.32 to 0.24
SecondaryCore Phase: Change From Last Dose in the ADAS-cog14 Word List (Immediate Recall and Delayed Recall) Score

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.

Time frame:
From last dose in the core phase (up to Month 24) up to 3 months follow-up (up to Month 27)
Reported as:
Least squares mean · score on a scale
Core Phase: Change From Last Dose in the ADAS-cog14 Word List (Immediate Recall and Delayed Recall) Score
score on a scaleCore Phase: PlaceboCore Phase: Elenbecestat 50 mg
Core Phase: Change From Last Dose in the ADAS-cog14 Word List (Immediate Recall and Delayed Recall) Score0.54 ± 0.0880.22 ± 0.090
Statistical analysis
  • Core Phase: Placebo vs Core Phase: Elenbecestat 50 mg · MMRM · p = 0.012 · Ls mean difference: -0.32 · 95% CI -0.56 to -0.07
SecondaryExtension Phase: Change From Core Phase Baseline up to Month 12 of the Extension Phase in CDR-SB Score

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.

Time frame:
Baseline (Day 1: before first dose in the core phase) up to Month 12 of the extension phase

No measurements were reported for this outcome.

SecondaryExtension Phase: Change From Core Phase Baseline up to Month 12 of the Extension Phase in ADCOMS

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.

Time frame:
Baseline (Day 1: before first dose in the core phase) up to Month 12 of the extension phase

No measurements were reported for this outcome.

SecondaryExtension Phase: Change From Core Phase Baseline up to Month 12 of the Extension Phase in MMSE Score

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.

Time frame:
Baseline (Day 1: before first dose in the core phase) up to Month 12 of the extension phase

No measurements were reported for this outcome.

SecondaryExtension Phase: Change From Core Phase Baseline up to Month 12 of the Extension Phase in FAQ Score

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").

Time frame:
Baseline (Day 1: before first dose in the core phase) up to Month 12 of the extension phase

No measurements were reported for this outcome.

SecondaryExtension Phase: Change From Core Phase Baseline up to Month 12 of the Extension Phase in ADAS-cog14 Score

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.

Time frame:
Baseline (Day 1: before first dose in the core phase) up to Month 12 of the extension phase

No measurements were reported for this outcome.

SecondaryExtension 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

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.

Time frame:
Baseline (Day 1: before first dose in the core phase) up to Month 12 of the extension phase

No measurements were reported for this outcome.

SecondaryExtension 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

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).

Time frame:
Baseline (Day 1: before first dose in the core phase) up to Month 12 of the extension phase

No measurements were reported for this outcome.

Adverse events

Collected over From first dose of study drug up to approximately 27 months (including 3 months follow up) for the Core Phase and up to approximately 6 months (including 1 month follow up) for the Extension Phase. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Core Phase: Placebo6/1,105 (0.5%)117/1,105 (10.6%)292/1,105 (26.4%)
Core Phase: Elenbecestat 50 mg3/1,099 (0.3%)134/1,099 (12.2%)391/1,099 (35.6%)
Extension Phase: Elenbecestat 50 mg0/18 (0%)0/18 (0%)6/18 (33.3%)
Most frequent serious events
Showing 10 of 236
Most frequent serious events
EventCore Phase: PlaceboCore Phase: Elenbecestat 50 mgExtension Phase: Elenbecestat 50 mg
FallInjury, poisoning and procedural complications4/11057/10990/18
OsteoarthritisMusculoskeletal and connective tissue disorders6/11051/10990/18
PneumoniaInfections and infestations3/11055/10990/18
InfluenzaInfections and infestations2/11055/10990/18
SyncopeNervous system disorders1/11054/10990/18
Urinary tract infectionInfections and infestations2/11053/10990/18
Hip fractureInjury, poisoning and procedural complications1/11053/10990/18
Femur fractureInjury, poisoning and procedural complications0/11053/10990/18
CataractEye disorders1/11053/10990/18
Breast cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)3/11051/10990/18
Most frequent other events
Showing 10 of 22
Most frequent other events
EventCore Phase: PlaceboCore Phase: Elenbecestat 50 mgExtension Phase: Elenbecestat 50 mg
Cognitive disorderNervous system disorders0/11050/10992/18
NasopharyngitisInfections and infestations67/110571/10990/18
LymphopeniaBlood and lymphatic system disorders18/110570/10990/18
Accidental overdoseInjury, poisoning and procedural complications55/110566/10990/18
ArthralgiaMusculoskeletal and connective tissue disorders0/11050/10991/18
OsteoarthritisMusculoskeletal and connective tissue disorders0/11050/10991/18
Pain in extremityMusculoskeletal and connective tissue disorders0/11050/10991/18
Cerebral microhaemorrhageNervous system disorders0/11050/10991/18
SomnolenceNervous system disorders0/11050/10991/18
Gait disturbanceGeneral disorders0/11050/10991/18

Baseline characteristics

The SAS was the group of participants who received at least 1 dose of study drug in the core phase and had at least 1 post-dose safety assessment.

Age, Continuous
Age, Continuous(years)Core Phase: PlaceboCore Phase: Elenbecestat 50 mgTotal
Mean72.1 ± 7.0971.9 ± 7.1872.0 ± 7.13
Sex: Female, Male
Sex: Female, Male(Participants)Core Phase: PlaceboCore Phase: Elenbecestat 50 mgTotal
Female5925341126
Male5135651078
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Core Phase: PlaceboCore Phase: Elenbecestat 50 mgTotal
Hispanic or Latino162158320
Not Hispanic or Latino9439411884
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Core Phase: PlaceboCore Phase: Elenbecestat 50 mgTotal
American Indian or Alaska Native101
Asian233247480
Native Hawaiian or Other Pacific Islander022
Black or African American122234
White8518171668
More than one race000
Unknown or Not Reported81119
08

Study locations

258 sites
  • Facility #1
    Chandler, Arizona 85226, United States
  • Facility #1
    Colton, California 92324, United States
  • Facility #1
    Costa Mesa, California 92626, United States
  • Facility #1
    Fullerton, California 92835, United States
  • Facility #1
    Imperial, California 92251, United States
  • Facility #1
    Irvine, California 92618, United States
  • Facility #1
    Lemon Grove, California 91945, United States
  • Facility #1
    Oceanside, California 92054, United States
  • Facility #2
    Oceanside, California 92054, United States
  • Facility #1
    Oxnard, California 93030, United States
  • Facility #1
    Panorama City, California 91402, United States
  • Facility #1
    San Diego, California 92123, United States
  • Facility #1
    Denver, Colorado 80218, United States
  • Facility #1
    Atlantis, Florida 33462, United States
  • Facility #1
    Aventura, Florida 33187, United States
  • Facility #2
    Aventura, Florida 33187, United States
  • Facility #1
    Boynton Beach, Florida 33437, United States
  • Facility #1
    Coral Gables, Florida 33134, United States
  • Facility #2
    Coral Gables, Florida 33134, United States
  • Facility #1
    Delray Beach, Florida 33445, United States
  • Facility #1
    Doral, Florida 33122, United States
  • Facility #1
    Hialeah, Florida 33016, United States
  • Facility #2
    Miami, Florida 33122, United States
  • Facility #11
    Miami, Florida 33125, United States
  • Facility #9
    Miami, Florida 33125, United States
  • Facility #10
    Miami, Florida 33126, United States
  • Facility #4
    Miami, Florida 33133, United States
  • Facility #1
    Miami, Florida 33137, United States
  • Facility #6
    Miami, Florida 33144, United States
  • Facility #3
    Miami, Florida 33155, United States
  • Facility #7
    Miami, Florida 33174, United States
  • Facility #8
    Miami, Florida 33176, United States
  • Facility #2
    Orlando, Florida 32801, United States
  • Facility #1
    Orlando, Florida 32806, United States
  • Facility #3
    Orlando, Florida 32807, United States
  • Facility #1
    Palm Beach Gardens, Florida 33410, United States
  • Facility #1
    Pompano Beach, Florida 33064, United States
  • Facility #1
    Port Charlotte, Florida 33952, United States
  • Facility #1
    Port Orange, Florida 32127, United States
  • Facility #1
    Spring Hill, Florida 34609, United States
  • Facility #1
    Tampa, Florida 33613, United States
  • Facility #2
    Tampa, Florida 33614, United States
  • Facility #1
    The Villages, Florida 32162, United States
  • Facility #1
    Atlanta, Georgia 30328, United States
  • Facility #1
    Columbus, Georgia 31909, United States
  • Facility #1
    Decatur, Georgia 30033, United States
  • Facility #1
    Suwanee, Georgia 30024, United States
  • Facility #1
    Meridian, Idaho 83642, United States
  • Facility #1
    Northbrook, Illinois 60062, United States
  • Facility #2
    Wichita, Kansas 67214, United States
  • Facility #1
    Boston, Massachusetts 2115, United States
  • Facility #1
    Farmington Hills, Michigan 48334, United States
  • Facility #1
    Chesterfield, Missouri 63005, United States
  • Facility #1
    O'Fallon, Missouri 63368, United States
  • Facility #2
    Saint Louis, Missouri 63104, United States
  • Facility #1
    Saint Peters, Missouri 63303, United States
  • Facility #1
    Mount Arlington, New Jersey 7856, United States
  • Facility #2
    Springfield, New Jersey 7081, United States
  • Facility #1
    West Long Branch, New Jersey 7764, United States
  • Facility #1
    Amherst, New York 14226, United States
  • Facility #1
    Brooklyn, New York 11229, United States
  • Facility #1
    New York, New York 10032, United States
  • Facility #1
    Canton, Ohio 44718, United States
  • Facility #1
    Centerville, Ohio 45459, United States
  • Facility #1
    Cleveland, Ohio 44195, United States
  • Facility #1
    Dayton, Ohio 45459, United States
  • Facility #1
    Lakewood, Ohio 44107, United States
  • Facility #1
    Westerville, Ohio 43081, United States
  • Facility #1
    Oklahoma City, Oklahoma 73116, United States
  • Facility #1
    Portland, Oregon 97210, United States
  • Facility #1
    Jenkintown, Pennsylvania 19046, United States
  • Facility #1
    Media, Pennsylvania 19063, United States
  • Facility #1
    Philadelphia, Pennsylvania 19104, United States
  • Facility #1
    East Providence, Rhode Island 02914, United States
  • Facility #1
    Providence, Rhode Island 2906, United States
  • Facility #1
    Port Royal, South Carolina 29935, United States
  • Facility #1
    Cordova, Tennessee 38018, United States
  • Facility #2
    Nashville, Tennessee 37203, United States
  • Facility #1
    Nashville, Tennessee 37212, United States
  • Facility #1
    Austin, Texas 78757, United States
  • Facility #1
    Dallas, Texas 75231, United States
  • Facility #1
    Houston, Texas 77084, United States
  • Facility #1
    San Antonio, Texas 78229-3900, United States
  • Facility #3
    San Antonio, Texas 78240, United States
  • Facility #1
    Salt Lake City, Utah 84108, United States
  • Facility #1
    Bennington, Vermont 5201, United States
  • Facility #1
    Hampton, Virginia 23666, United States
  • Facility #1
    Madison, Wisconsin 53705, United States
  • Facility #2
    Caba, Buenos Aires -1405, Argentina
  • Facility #1
    Caba, Buenos Aires C1012AAR, Argentina
  • Facility #4
    Caba, Buenos Aires C1126AAB, Argentina
  • Facility #3
    Caba, Buenos Aires C1427, Argentina
  • Facility #1
    Ciudad Autonoma de Buenos Aires, Buenos Aires 1111, Argentina
  • Facility #3
    Ciudad Autonoma de Buenos Aires, Buenos Aires 1430, Argentina
  • Facility #2
    Ciudad Autonoma de Buenos Aires, Buenos Aires C1230AAZ, Argentina
  • Facility #1
    Cordoba, Capital X5003DCE, Argentina
  • Facility #1
    Rosario, Santa Fe 2000, Argentina
  • Facility #4
    Buenos Aires, 1199, Argentina
  • Facility #5
    Caba, C1428AQK, Argentina
  • Facility #2
    Cordoba, X5004A0A, Argentina

Showing the first 100 of 258 sites across 18 countries.

09

References and documents

Publications

  • Bullich S, Mueller A, De Santi S, Koglin N, Krause S, Kaplow J, Kanekiyo M, Roe-Vellve N, Perrotin A, Jovalekic A, Scott D, Gee M, Stephens A, Irizarry M. Evaluation of tau deposition using 18F-PI-2620 PET in MCI and early AD subjects-a MissionAD tau sub-study. Alzheimers Res Ther. 2022 Jul 27;14(1):105. doi: 10.1186/s13195-022-01048-x. PubMed 35897078 ↗

Study documents

  • Study protocol · May 23, 2019
  • Statistical analysis plan · Mar 19, 2020

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Undecided

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Feb 3, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02956486
Lead sponsor
Eisai Co., Ltd.
Collaborators
Biogen
Responsible party
Sponsor
First posted
Nov 6, 2016
Start date
Oct 20, 2016
Primary completion
Jan 15, 2020
Completion
Jan 15, 2020
Results posted
Feb 3, 2021
Last update
Feb 3, 2021

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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