Trial · NCT02956486
A 24-Month Study to Evaluate the Efficacy and Safety of Elenbecestat (E2609) in Participants With Early Alzheimer's Disease
NCT02956486, Phase 3, Terminated, Eisai Co., Ltd.; results first posted 2021-02-03
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ConductScience Library. A 24-Month Study to Evaluate the Efficacy and Safety of Elenbecestat (E2609) in Participants With Early Alzheimer's Disease. Trials, record NCT02956486. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT02956486
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- A 24-Month Study to Evaluate the Efficacy and Safety of Elenbecestat (E2609) in Participants With Early Alzheimer's Disease
- NCT number
- NCT02956486
- Status
- Terminated
- Phases
- Phase 3
- Enrollment
- 2,212 participants, actual
- Lead sponsor
- Eisai Co., Ltd.
- Conditions
- Alzheimer's Disease
- Interventions
- Elenbecestat, Placebo
- First posted
- 2016-11-07
- Last updated
- 2021-02-03
- Other registries' IDs
- eudract:2016-003928-23, eudract:2016-004128-42
- Results first posted
- 2021-02-03
- 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.
Source ClinicalTrials.gov
Registered outcomes27
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Core Phase: Change From Baseline up to Month 24 in the Clinical Dementia Rating-sum of Boxes (CDR-SB) Score | Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase | 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. |
| Primary | Extension Phase: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | From first dose of study drug up to approximately 6 months (including 1 month follow up) for the extension phase | 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. |
| Secondary | Core Phase: Change From Baseline up to Month 24 in Alzheimer's Disease Composite Score (ADCOMS) | Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase | 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. |
| Secondary | Core Phase: Change From Baseline up to Month 24 in Amyloid Positron Emission Tomography (PET) Standardized Uptake Value Ratio (SUVR) | Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase | 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. |
| Secondary | 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 | Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase | 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. |
| Secondary | 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 | Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase | 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. |
| Secondary | Core Phase: Change Per Year (Mean Slope) in CDR-SB Score up to Month 24 | Up to Month 24 of the core phase | 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. |
| Secondary | Core Phase: Time to Worsening of CDR Score up to Month 24 | Up to Month 24 of the core phase | 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. |
| Secondary | 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 | Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core 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). |
| Secondary | Core Phase: Change From Baseline up to Month 24 in the Alzheimer's Disease Assessment Scale-cognition14 (ADAS-Cog14) Score | Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase | 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. |
1 to 10 of 27Source ClinicalTrials.gov
See all 27 registered outcomesOutcomes27
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Core Phase: Change From Baseline up to Month 24 in the Clinical Dementia Rating-sum of Boxes (CDR-SB) Score | Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase | The FAS was the group of randomized participants who received at least 1 dose of study drug in the core phase and had baseline and at least 1 post-dose primary efficacy measurement. Here overall number of participants analyzed signifies all participants included in mixed effects model for repeated measures (MMRM) who were evaluable for this specific outcome measure. | score on a scale | LEAST_SQUARES_MEAN |
| PRIMARY | Extension Phase: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | From first dose of study drug up to approximately 6 months (including 1 month follow up) for the extension phase | All safety participants was the group of participants who enrolled into the extension phase and received at least 1 dose of study drug in the extension phase. | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | Core Phase: Change From Baseline up to Month 24 in Alzheimer's Disease Composite Score (ADCOMS) | Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase | The FAS was the group of randomized participants who received at least 1 dose of study drug in the core phase and had baseline and at least 1 post-dose primary efficacy measurement. Here overall number of participants analyzed signifies all participants included in MMRM who were evaluable for this specific outcome measure. | score on a scale | LEAST_SQUARES_MEAN |
| SECONDARY | Core Phase: Change From Baseline up to Month 24 in Amyloid Positron Emission Tomography (PET) Standardized Uptake Value Ratio (SUVR) | Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase | The pharmacodynamic (PD) analysis set was the group of participants in the core phase who had sufficient PD data to derive at least 1 PD parameter. Here overall number of participants analyzed signifies all participants included in MMRM who were evaluable for this specific outcome measure. | score on a scale | LEAST_SQUARES_MEAN |
| SECONDARY | 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 | Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase | The FAS was the group of randomized participants who received at least 1 dose of study drug in the core phase and had baseline and at least 1 post-dose primary efficacy measurement. Here overall number of participants analyzed signifies all participants included in MMRM who were evaluable for this specific outcome measure. | score on a scale | LEAST_SQUARES_MEAN |
| SECONDARY | 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 | Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase | The FAS was the group of randomized participants who received at least 1 dose of study drug in the core phase and had baseline and at least 1 post-dose primary efficacy measurement. Here overall number of participants analyzed signifies all participants included in MMRM who were evaluable for this specific outcome measure. | score on a scale | LEAST_SQUARES_MEAN |
| SECONDARY | Core Phase: Change Per Year (Mean Slope) in CDR-SB Score up to Month 24 | Up to Month 24 of the core phase | The FAS was the group of randomized participants who received at least 1 dose of study drug in the core phase and had baseline and at least 1 post-dose primary efficacy measurement. | change in score per year | LEAST_SQUARES_MEAN |
| SECONDARY | Core Phase: Time to Worsening of CDR Score up to Month 24 | Up to Month 24 of the core phase | The FAS was the group of randomized participants who received at least 1 dose of study drug in the core phase and had baseline and at least 1 post-dose primary efficacy measurement. | months | MEDIAN |
| SECONDARY | 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 | Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase | The FAS was the group of randomized participants who received at least 1 dose of study drug in the core phase and had baseline and at least 1 post-dose primary efficacy measurement. Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure. | months | MEDIAN |
| SECONDARY | Core Phase: Change From Baseline up to Month 24 in the Alzheimer's Disease Assessment Scale-cognition14 (ADAS-Cog14) Score | Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase | The FAS was the group of randomized participants who received at least 1 dose of study drug in the core phase and had baseline and at least 1 post-dose primary efficacy measurement. Here overall number of participants analyzed signifies all participants included in MMRM who were evaluable for this specific outcome measure. | score on a scale | LEAST_SQUARES_MEAN |
1 to 10 of 27Source ClinicalTrials.gov
See all 27 outcomesResults by group39
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Core Phase: Change From Baseline up to Month 24 in the Clinical Dementia Rating-sum of Boxes (CDR-SB) Score | Core Phase: Placebo | 2.17 | Standard Error 0.142 | score on a scale | |
| Core Phase: Change From Baseline up to Month 24 in the Clinical Dementia Rating-sum of Boxes (CDR-SB) Score | Core Phase: Elenbecestat 50 mg | 1.99 | Standard Error 0.146 | score on a scale | |
| Extension Phase: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) | Extension Phase: Elenbecestat 50 mg | 6 | Participants | ||
| Core Phase: Change From Baseline up to Month 24 in Alzheimer's Disease Composite Score (ADCOMS) | Core Phase: Placebo | 0.24 | Standard Error 0.014 | score on a scale | |
| Core Phase: Change From Baseline up to Month 24 in Alzheimer's Disease Composite Score (ADCOMS) | Core Phase: Elenbecestat 50 mg | 0.23 | Standard Error 0.015 | score on a scale | |
| Core Phase: Change From Baseline up to Month 24 in Amyloid Positron Emission Tomography (PET) Standardized Uptake Value Ratio (SUVR) | Core Phase: Placebo | 7.81 | Standard Error 2.500 | score on a scale | |
| Core Phase: Change From Baseline up to Month 24 in Amyloid Positron Emission Tomography (PET) Standardized Uptake Value Ratio (SUVR) | Core Phase: Elenbecestat 50 mg | -5.02 | Standard Error 2.046 | 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 | Core Phase: Placebo | 1.97 | Standard Error 0.157 | 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 | Core Phase: Elenbecestat 50 mg | 1.74 | Standard Error 0.169 | 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 | Core Phase: Placebo | 0.23 | Standard Error 0.017 | score on a scale |
1 to 10 of 39Source ClinicalTrials.gov
See all 39 results by groupParticipant flow33
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Core Phase | STARTED | Core Phase: Placebo | 1,108 | |
| Core Phase | STARTED | Core Phase: Elenbecestat 50 mg | 1,104 | |
| Core Phase | STARTED | Extension Phase: Elenbecestat 50 mg | 0 | |
| Core Phase | Treated | Core Phase: Placebo | 1,108 | |
| Core Phase | Treated | Core Phase: Elenbecestat 50 mg | 1,101 | |
| Core Phase | Treated | Extension Phase: Elenbecestat 50 mg | 0 | |
| Core Phase | Safety Analysis Set (SAS) | Core Phase: Placebo | 1,105 | |
| Core Phase | Safety Analysis Set (SAS) | Core Phase: Elenbecestat 50 mg | 1,099 | |
| Core Phase | Safety Analysis Set (SAS) | Extension Phase: Elenbecestat 50 mg | 0 | |
| Core Phase | Full Analysis Set (FAS) | Core Phase: Placebo | 1,084 |
1 to 10 of 33Source ClinicalTrials.gov
See all 33 participant flowAdverse events774
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Lymphopenia | Blood and lymphatic system disorders | Core Phase: Placebo | 18 | 1,105 | 18 |
| other | Lymphopenia | Blood and lymphatic system disorders | Core Phase: Elenbecestat 50 mg | 70 | 1,099 | 89 |
| other | Lymphopenia | Blood and lymphatic system disorders | Extension Phase: Elenbecestat 50 mg | 0 | 18 | 0 |
| other | Nasopharyngitis | Infections and infestations | Core Phase: Placebo | 67 | 1,105 | 80 |
| other | Nasopharyngitis | Infections and infestations | Core Phase: Elenbecestat 50 mg | 71 | 1,099 | 86 |
| other | Nasopharyngitis | Infections and infestations | Extension Phase: Elenbecestat 50 mg | 0 | 18 | 0 |
| other | Upper respiratory tract infection | Infections and infestations | Core Phase: Placebo | 50 | 1,105 | 56 |
| other | Upper respiratory tract infection | Infections and infestations | Core Phase: Elenbecestat 50 mg | 58 | 1,099 | 63 |
| other | Upper respiratory tract infection | Infections and infestations | Extension Phase: Elenbecestat 50 mg | 0 | 18 | 0 |
| other | Accidental overdose | Injury, poisoning and procedural complications | Core Phase: Placebo | 55 | 1,105 | 79 |
1 to 10 of 774Source ClinicalTrials.gov
See all 774 adverse eventsAdverse event totals9
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Core Phase: Placebo | 6 | 1,105 |
| Total, all-cause mortality | Core Phase: Elenbecestat 50 mg | 3 | 1,099 |
| Total, all-cause mortality | Extension Phase: Elenbecestat 50 mg | 0 | 18 |
| Total, other adverse events | Core Phase: Placebo | 292 | 1,105 |
| Total, other adverse events | Core Phase: Elenbecestat 50 mg | 391 | 1,099 |
| Total, other adverse events | Extension Phase: Elenbecestat 50 mg | 6 | 18 |
| Total, serious adverse events | Core Phase: Placebo | 117 | 1,105 |
| Total, serious adverse events | Core Phase: Elenbecestat 50 mg | 134 | 1,099 |
| Total, serious adverse events | Extension Phase: Elenbecestat 50 mg | 0 | 18 |
Source ClinicalTrials.gov
Papers3
The papers the trial lists on ClinicalTrials.gov.
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons0
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
None in this release.
Tests1
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
| Test | Named as |
|---|---|
| Delayed Recall Module | Secondary outcome |
Source ConductCognition
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
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