Clinical Trials List
Protocol NumberE2609-G000-302
NCT Number(ClinicalTrials.gov Identfier)NCT03036280
2017-06-01 - 2019-12-31
Phase III
Terminated11
ICD-10F03.90
Unspecified dementia without behavioral disturbance
ICD-10G30.9
Alzheimer's disease, unspecified
ICD-10G30
Alzheimer's disease
ICD-9331.0
Alzheimer's disease
A Placebo-Controlled, Double-Blind, Parallel-Group, 24 Month Study With an Open-Label Extension Phase to Evaluate the Efficacy and Safety of Elenbecestat (E2609) in Subjects With Early Alzheimer's Disease
-
Trial Applicant
Syneos Health
-
Sponsor
Eisai Co., Ltd.
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- 陳韋達 Division of Neurology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- 張維紘 Division of Neurology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Co-Principal Investigator
- 王炯堯 Division of Neurology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Chon-Haw Tsai Division of Neurology
- Yi-Ting Hsu Division of Neurology
- Fu-Yu Lin Division of Neurology
- Wei-Shih Huang Division of Neurology
- Kuan-Fei Chen Division of Neurology
- Kang-Hsu Lin Division of Neurology
- Hui-Chun Huang Division of Neurology
- Yuh-Cherng Guo Division of Neurology
- Ming-Kuei Lu Division of Neurology
- Ching-Hua Lu Lu Division of Neurology
- Jui-Cheng Chen Division of Neurology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- 詹博棋 Division of Neurology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
Audit
CRO
Linkou Chang Gung Medical Foundation
Taiwan National PI
黃錦章
Co-Principal Investigator
- KuoLun Huang Division of Neurology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Co-Principal Investigator
Audit
CRO
Co-Principal Investigator
- YA-FANG CHEN Division of Radiology
- RUOH-FANG YEN Division of Nuclear Medicine
- TA-FU CHEN Division of Neurology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Yi-Chun Kuan Division of Neurology
- Shu-Ping Chao Division of Neurology
- Li-Kai Huang Division of Neurology
- YAO-TUNG LEE Division of Neurology
The Actual Total Number of Participants Enrolled
1 Stop recruiting
Audit
None
Condition/Disease
Alzheimer's Disease
Objectives
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.
Test Drug
Elenbecestat (E2609)
Active Ingredient
Elenbecestat
Dosage Form
tablet
Dosage
50
Endpoints
Primary Endpoint
Change from baseline in the CDR-SB at 24 months
Secondary Endpoints
Time to worsening of CDR scores by 24 months (eg, the worsening of global CDR score is
defined as an increase from baseline by at least 0.5 points on the global CDR scale on
2 consecutive scheduled visits at which global CDR is undertaken)
Time to conversion to dementia by 24 months for subjects who were not clinically staged as
dementia at Baseline based on clinical diagnosis
The rate of change over time (mean slope) based on CDR-SB score over 24 months
Change from baseline in CDR-SB at 27 months (ie, 24 months of treatment plus 3 months
posttreatment follow-up)
Change from baseline in ADAS-cog14, MMSE, and FAQ at 24 months
Change from baseline in ADAS-cog14 Word List (immediate recall and delayed recall) at
24 months
Biomarker Endpoints
Change from baseline in amyloid PET SUVR composite at 24 months for brain amyloid
levels
Change from baseline in CSF biomarkers t-tau and p-tau at 24 months
Change from baseline in CSF amyloid biomarkers Aβ(1-40), Aβ(1-42), and Aβ(1-x) at
24 months
Change from baseline in total hippocampal volume at 24 months using vMRI
Change from baseline in the preservation of connectivity on fMRI at 24 months
Exploratory Endpoints
Time to change of concomitant AD treatment (ie, dose increase and/or initiation of treatment
with AChEI or memantine after randomization) by 24 months
The proportion of subjects at 24 months who received dose increases and/or initiation of
treatment with AChEI or memantine after randomization
The rate of change over time (mean slope) based on NPI-10 item score over 24 months
Change from baseline in NPI-10 item at 24 months
Change from baseline in EQ-5D (subject self-reported, study partner self-reported, and
subject measured by proxy) and QOL-AD (subject and study partner) at 24 months
Change from baseline in the CDR-SB at 24 months
Secondary Endpoints
Time to worsening of CDR scores by 24 months (eg, the worsening of global CDR score is
defined as an increase from baseline by at least 0.5 points on the global CDR scale on
2 consecutive scheduled visits at which global CDR is undertaken)
Time to conversion to dementia by 24 months for subjects who were not clinically staged as
dementia at Baseline based on clinical diagnosis
The rate of change over time (mean slope) based on CDR-SB score over 24 months
Change from baseline in CDR-SB at 27 months (ie, 24 months of treatment plus 3 months
posttreatment follow-up)
Change from baseline in ADAS-cog14, MMSE, and FAQ at 24 months
Change from baseline in ADAS-cog14 Word List (immediate recall and delayed recall) at
24 months
Biomarker Endpoints
Change from baseline in amyloid PET SUVR composite at 24 months for brain amyloid
levels
Change from baseline in CSF biomarkers t-tau and p-tau at 24 months
Change from baseline in CSF amyloid biomarkers Aβ(1-40), Aβ(1-42), and Aβ(1-x) at
24 months
Change from baseline in total hippocampal volume at 24 months using vMRI
Change from baseline in the preservation of connectivity on fMRI at 24 months
Exploratory Endpoints
Time to change of concomitant AD treatment (ie, dose increase and/or initiation of treatment
with AChEI or memantine after randomization) by 24 months
The proportion of subjects at 24 months who received dose increases and/or initiation of
treatment with AChEI or memantine after randomization
The rate of change over time (mean slope) based on NPI-10 item score over 24 months
Change from baseline in NPI-10 item at 24 months
Change from baseline in EQ-5D (subject self-reported, study partner self-reported, and
subject measured by proxy) and QOL-AD (subject and study partner) at 24 months
Inclution Criteria
Inclusion Criteria
Subjects must meet all of the following criteria to be included in this study
1. MCI due to Alzheimer’s disease or Mild Alzheimer’s disease according to the National Institute
of Aging – Alzheimer’s Association (NIA-AA) core clinical criteria and must have all of the
following:
a. MMSE score equal to or greater than 24
b. CDR global score of 0.5
c. CDR Memory Box score of 0.5 or greater
2. A history of subjective memory decline with gradual onset and slow progression over the last
1 year before Screening; this MUST be corroborated by a study partner
3. Cognitive impairment of at least 1 SD from age-adjusted norms in total recall or delayed recall on
the ISLT.
4. Positive biomarker for brain amyloid pathology as indicated by at least 1 of the following:
a. PET assessment of amyloid imaging agent uptake into brain. Note: amyloid PET screens
will be performed according to local regulatory guidelines and thus may be restricted for
those subjects who are not suitable for lumbar puncture (LP) to obtain CSF for testing of
eligibility.
b. CSF assessment of Aβ(1-42)
NOTE: Subjects may undergo both the amyloid PET and CSF assessments, but need a
positive amyloid result in only 1 of the 2 procedures to confirm eligibility. Subjects who
consent to amyloid PET or CSF for eligibility purposes are not required to participate in the
amyloid PET or CSF longitudinal substudies. Use of a historical amyloid PET (conducted
within 12 months before the planned date of randomization) is acceptable for determination
of eligibility but will not suffice for the baseline assessment if the subject wishes to consent
to the amyloid PET longitudinal substudy. The historical imaging data must be made
available to the sponsor.
5. Male or female subjects between 50 and 85 years of age, inclusive at the time of consent
6. If receiving an AChEI or memantine or both for AD, must be on a stable dose for at least
12 weeks prior to Randomization. Treatment-naïve subjects with AD can be entered into the study.
7. Subjects must have been on stable doses of all other (ie, non-AD related) permitted concomitant
medications for at least 4 weeks prior to Randomization, except for medications which are
administered as short courses (eg, up to 3 weeks unless discussed and agreed with Medical
Monitor) of treatment (eg, anti-infectives, oral steroids) or which are to be used on a Pro re nata
(PRN) basis. Subjects who require a short course of treatment, such as anti-infectives or oral
steroids, may be randomized once the acute illness has completely resolved, even if the
concomitant medication continues.
8. Must have an identified study partner (defined as a person able to support the subject for the
duration of the study and who spends at least 8 hours per week with the subject). The study partner must provide written informed consent. In addition, this person must be willing and able
to provide follow-up information on the subject throughout the course of the study. This person
must, in the opinion of the investigator, spend sufficient time with the subject on a regular basis
such that they can reliably fulfill the requirements of being a study partner. A study partner need
not be living in the same residence with the subject. For such a study partner not residing with
the subject, the investigator has to be satisfied that the subject can contact the study partner
readily during the times when the study partner is not with the subject. Study partners need to
provide input to the following assessments: CDR, FAQ, EQ-5D, QOL-AD, Zarit’s Burden
Interview, NPI-10, and the clinical assessment of suicidality. Consideration can occur for the
investigator to decide whether the study partner can provide information over the telephone or
whether the study partner must attend the study visits in person with the subject.
Subjects must meet all of the following criteria to be included in this study
1. MCI due to Alzheimer’s disease or Mild Alzheimer’s disease according to the National Institute
of Aging – Alzheimer’s Association (NIA-AA) core clinical criteria and must have all of the
following:
a. MMSE score equal to or greater than 24
b. CDR global score of 0.5
c. CDR Memory Box score of 0.5 or greater
2. A history of subjective memory decline with gradual onset and slow progression over the last
1 year before Screening; this MUST be corroborated by a study partner
3. Cognitive impairment of at least 1 SD from age-adjusted norms in total recall or delayed recall on
the ISLT.
4. Positive biomarker for brain amyloid pathology as indicated by at least 1 of the following:
a. PET assessment of amyloid imaging agent uptake into brain. Note: amyloid PET screens
will be performed according to local regulatory guidelines and thus may be restricted for
those subjects who are not suitable for lumbar puncture (LP) to obtain CSF for testing of
eligibility.
b. CSF assessment of Aβ(1-42)
NOTE: Subjects may undergo both the amyloid PET and CSF assessments, but need a
positive amyloid result in only 1 of the 2 procedures to confirm eligibility. Subjects who
consent to amyloid PET or CSF for eligibility purposes are not required to participate in the
amyloid PET or CSF longitudinal substudies. Use of a historical amyloid PET (conducted
within 12 months before the planned date of randomization) is acceptable for determination
of eligibility but will not suffice for the baseline assessment if the subject wishes to consent
to the amyloid PET longitudinal substudy. The historical imaging data must be made
available to the sponsor.
5. Male or female subjects between 50 and 85 years of age, inclusive at the time of consent
6. If receiving an AChEI or memantine or both for AD, must be on a stable dose for at least
12 weeks prior to Randomization. Treatment-naïve subjects with AD can be entered into the study.
7. Subjects must have been on stable doses of all other (ie, non-AD related) permitted concomitant
medications for at least 4 weeks prior to Randomization, except for medications which are
administered as short courses (eg, up to 3 weeks unless discussed and agreed with Medical
Monitor) of treatment (eg, anti-infectives, oral steroids) or which are to be used on a Pro re nata
(PRN) basis. Subjects who require a short course of treatment, such as anti-infectives or oral
steroids, may be randomized once the acute illness has completely resolved, even if the
concomitant medication continues.
8. Must have an identified study partner (defined as a person able to support the subject for the
duration of the study and who spends at least 8 hours per week with the subject). The study partner must provide written informed consent. In addition, this person must be willing and able
to provide follow-up information on the subject throughout the course of the study. This person
must, in the opinion of the investigator, spend sufficient time with the subject on a regular basis
such that they can reliably fulfill the requirements of being a study partner. A study partner need
not be living in the same residence with the subject. For such a study partner not residing with
the subject, the investigator has to be satisfied that the subject can contact the study partner
readily during the times when the study partner is not with the subject. Study partners need to
provide input to the following assessments: CDR, FAQ, EQ-5D, QOL-AD, Zarit’s Burden
Interview, NPI-10, and the clinical assessment of suicidality. Consideration can occur for the
investigator to decide whether the study partner can provide information over the telephone or
whether the study partner must attend the study visits in person with the subject.
Exclusion Criteria
Exclusion Criteria
Subjects who meet any of the following criteria will be excluded from this study:
1. Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive
beta-human chorionic gonadotropin test. A separate baseline assessment is required if a negative
screening pregnancy test was obtained more than 72 hours before the first dose of study drug.
Females of child-bearing potential who:
Within 28 days before study entry, did not use a highly effective method of contraception,
which includes any of the following:
o total abstinence (if it is their preferred and usual lifestyle)
o an intrauterine device or intrauterine hormone-releasing system
o an oral contraceptive (Subject must be on a stable dose of the same oral
contraceptive product for at least 28 days before dosing and throughout the study and
for 28 days after study drug discontinuation.)
o have a vasectomized partner with confirmed azoospermia.
Do not agree to use a highly effective method of contraception (as described above)
throughout the entire study period and for 28 days after study drug discontinuation.
For sites outside of the European Union, it is permissible that if a highly effective method of
contraception is not appropriate or acceptable to the subject, then the subject must agree to use a
medically acceptable method of contraception, ie, double-barrier methods of contraception such
as condom plus diaphragm or cervical/vault cap with spermicide.
NOTE: All females will be considered to be of child-bearing potential unless they are
postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group,
and without other known or suspected cause) or have been sterilized surgically (ie, bilateral tubal
ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before
dosing)
2. Any condition that may be contributing to cognitive impairment above and beyond that caused by
the subject’s AD
3. Subjects with a history of seizures within 5 years of Screening or subjects with disturbance likely
to be due to seizures within 5 years of Screening
4. History of transient ischemic attacks (TIA) or stroke within 12 months of Screening
5. Modified Hachinski Ischemia Score greater than 4 at Screening
6. Any of the following psychiatric symptoms:
• Psychiatric diagnosis or symptoms, (eg, hallucinations, major depression, or delusions)
that, in the opinion of the investigator, could interfere with study procedures
• Has a “yes” answer to C-SSRS suicidal ideation items 4 or 5, or any suicidal behavior
within 6 months before Screening, at Screening, or at the Randomization Visit, or has been
hospitalized or treated for suicidal behavior in the past 5 years before Screening
7. Have any contraindications to MRI scanning, including cardiac pacemaker/defibrillator,
ferromagnetic metal implants (eg, in skull and cardiac devices other than those approved as safe
for use in MRI scanners) or
• Have any evidence of other clinically significant lesions that could indicate a dementia
diagnosis other than AD on brain MRI at Screening.
• Exhibit other significant pathological findings on brain MRI at Screening, including but not
limited to: an area of superficial siderosis; evidence of cerebral vasogenic edema; evidence
of cerebral contusion, encephalomalacia, aneurysms, vascular malformations, or infective
lesions; evidence of multiple lacunar infarcts or stroke involving a major vascular territory,
severe small vessel, or white matter disease; space occupying lesions; or brain tumors
(however, lesions diagnosed as meningiomas or arachnoid cysts and less than 1 cm at their
greatest diameter need not be exclusionary).
8. Subjects who have a history of moderate to severe hepatic impairment (eg, Child-Pugh Class B or
C). Any 2 of the following criteria at Screening would exclude the subject: INR ≥ 1.7; bilirubin
≥ 1.5 × ULN; albumin < LLN; ascites or hepatic encephalopathy. Please note that a single
significant abnormality could meet criteria for moderate impairment. (revised per
Amendment 01)
9. Results of laboratory tests conducted during screening that are outside the following limits:
• Absolute lymphocyte count (ALC) below Lower Limit of Normal (LLN) or below
800 per mm3 (whichever is higher); ALC will be derived from the complete blood count
(CBC) with differential representing the normal lymphocytes (with atypical lymphocytes
removed and presented as a separate count if they are present) and calculated by the white
blood cell count × percentage of lymphocytes. (revised per Amendment 01)
• Thyroid stimulating hormone (TSH) above normal range. Other tests of thyroid function
with results outside the normal range should only be exclusionary if they are considered
clinically significant by the investigator (this applies to all subjects whether or not they are
taking thyroid supplements)
• Abnormally low (below LLN) serum Vitamin B12 levels (if subject is taking Vitamin B12
injections, level should be at or above the LLN)
10. Subjects at risk of increased risk of infection, specifically:
• Subjects with chronic viral hepatitis, a history of active tuberculosis disease (TB),
ophthalmic shingles or ocular herpes simplex virus (HSV) infection
• Any active infection within the last 4 weeks before randomization. For such cases, the
timing of randomization can be extended (up to 4 weeks) to allow the infection to resolve
• Any immunological disease which is not adequately controlled, or which requires treatment
with biologic drugs during the study. History of immunoglobulin (Ig) deficiency or other
immunodeficiency disorders (including subjects known to be HIV positive)
11. Have received any live/live attenuated vaccine in the 3 months before randomization
12. Any chronic inflammatory disease that is not adequately controlled or that requires systemic or
ocular immunosuppressive or immunomodulatory therapy.
NOTE: The following subjects do not need to be excluded:
• Subjects with seasonal or perennial allergic rhinitis, asthma, or chronic obstructive
pulmonary disease where the condition is considered to be stable and adequately controlled
by inhaled steroids.
• Hashimoto’s thyroiditis but who are stable on thyroid replacement therapy and not on
systemic immunosuppressive therapy.
• Cutaneous manifestations of immunological disease that do not require systemic
immunosuppressive therapy or systemic immunomodulatory therapy (ie, topical steroid
treatment is permitted)
13. Any other clinically significant abnormalities, such as:
• Physical examination, vital signs, laboratory tests or ECG at Screening or Baseline which
in the opinion of the investigator require further investigation or treatment or which may
interfere with study procedures or safety.
• Other medical conditions (eg, cardiac, respiratory, gastrointestinal, psychiatric, renal
disease) which are not adequately and stably controlled, or which in the opinion of the
investigator(s) could affect the subject’s safety or interfere with the study assessments
(revised per Amendment 01)
• Illiteracy, or severe visual or hearing impairment that would prevent the subject from
performing psychometric tests accurately
14. A prolonged QTc interval calculated using Fridericia’s formula (QTcF) interval (QTcF greater
than 450 ms). If the QTcF is greater than 450 ms on the first single 12-lead ECG, 2 additional
12-lead ECGs will be performed 1 minute apart and the mean of the 3 QTcF values will be
calculated.
15. Malignant neoplasms within 5 years of Screening (except for basal or squamous cell carcinoma in
situ of the skin, or localized prostate cancer in male subjects with treatment cycles completed at
least 6 months prior to screening). Subjects who had malignant neoplasms but who have had at
least 5 years of documented uninterrupted remission before Screening need not be excluded.
16. Hypopigmentation conditions (eg, albinism and vitiligo). Hypopigmentation associated with
scarring need not be exclusionary
17. Known or suspected history of drug or alcohol abuse or dependence within 2 years before
Screening
18. Taking prohibited medications
19. Have participated in a clinical study involving:
• any therapeutic monoclonal antibody, protein derived from a monoclonal antibody,
immunoglobulin therapy, or vaccine within 6 months before Screening for whom it cannot
be documented that they were randomized only to placebo or never received study drug
• elenbecestat (E2609)
• any new chemical entity for AD with last study drug dose occurring within 6 months prior to
Screening unless it can be documented that the subject received only placebo
• any other investigational medication (unless it can be documented that the subject received
only placebo) or device within 8 weeks or 5 half-lives (whichever is longer) before
randomization
20. Planned surgery which requires general, spinal or epidural anesthesia that would take place
during the study. Planned surgery which requires only local anesthesia and which can be
undertaken as day case without inpatient stay postoperatively need not result in exclusion if in the
opinion of the investigator this operation does not interfere with study procedures and subject
safety.
Subjects who meet any of the following criteria will be excluded from this study:
1. Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive
beta-human chorionic gonadotropin test. A separate baseline assessment is required if a negative
screening pregnancy test was obtained more than 72 hours before the first dose of study drug.
Females of child-bearing potential who:
Within 28 days before study entry, did not use a highly effective method of contraception,
which includes any of the following:
o total abstinence (if it is their preferred and usual lifestyle)
o an intrauterine device or intrauterine hormone-releasing system
o an oral contraceptive (Subject must be on a stable dose of the same oral
contraceptive product for at least 28 days before dosing and throughout the study and
for 28 days after study drug discontinuation.)
o have a vasectomized partner with confirmed azoospermia.
Do not agree to use a highly effective method of contraception (as described above)
throughout the entire study period and for 28 days after study drug discontinuation.
For sites outside of the European Union, it is permissible that if a highly effective method of
contraception is not appropriate or acceptable to the subject, then the subject must agree to use a
medically acceptable method of contraception, ie, double-barrier methods of contraception such
as condom plus diaphragm or cervical/vault cap with spermicide.
NOTE: All females will be considered to be of child-bearing potential unless they are
postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group,
and without other known or suspected cause) or have been sterilized surgically (ie, bilateral tubal
ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before
dosing)
2. Any condition that may be contributing to cognitive impairment above and beyond that caused by
the subject’s AD
3. Subjects with a history of seizures within 5 years of Screening or subjects with disturbance likely
to be due to seizures within 5 years of Screening
4. History of transient ischemic attacks (TIA) or stroke within 12 months of Screening
5. Modified Hachinski Ischemia Score greater than 4 at Screening
6. Any of the following psychiatric symptoms:
• Psychiatric diagnosis or symptoms, (eg, hallucinations, major depression, or delusions)
that, in the opinion of the investigator, could interfere with study procedures
• Has a “yes” answer to C-SSRS suicidal ideation items 4 or 5, or any suicidal behavior
within 6 months before Screening, at Screening, or at the Randomization Visit, or has been
hospitalized or treated for suicidal behavior in the past 5 years before Screening
7. Have any contraindications to MRI scanning, including cardiac pacemaker/defibrillator,
ferromagnetic metal implants (eg, in skull and cardiac devices other than those approved as safe
for use in MRI scanners) or
• Have any evidence of other clinically significant lesions that could indicate a dementia
diagnosis other than AD on brain MRI at Screening.
• Exhibit other significant pathological findings on brain MRI at Screening, including but not
limited to: an area of superficial siderosis; evidence of cerebral vasogenic edema; evidence
of cerebral contusion, encephalomalacia, aneurysms, vascular malformations, or infective
lesions; evidence of multiple lacunar infarcts or stroke involving a major vascular territory,
severe small vessel, or white matter disease; space occupying lesions; or brain tumors
(however, lesions diagnosed as meningiomas or arachnoid cysts and less than 1 cm at their
greatest diameter need not be exclusionary).
8. Subjects who have a history of moderate to severe hepatic impairment (eg, Child-Pugh Class B or
C). Any 2 of the following criteria at Screening would exclude the subject: INR ≥ 1.7; bilirubin
≥ 1.5 × ULN; albumin < LLN; ascites or hepatic encephalopathy. Please note that a single
significant abnormality could meet criteria for moderate impairment. (revised per
Amendment 01)
9. Results of laboratory tests conducted during screening that are outside the following limits:
• Absolute lymphocyte count (ALC) below Lower Limit of Normal (LLN) or below
800 per mm3 (whichever is higher); ALC will be derived from the complete blood count
(CBC) with differential representing the normal lymphocytes (with atypical lymphocytes
removed and presented as a separate count if they are present) and calculated by the white
blood cell count × percentage of lymphocytes. (revised per Amendment 01)
• Thyroid stimulating hormone (TSH) above normal range. Other tests of thyroid function
with results outside the normal range should only be exclusionary if they are considered
clinically significant by the investigator (this applies to all subjects whether or not they are
taking thyroid supplements)
• Abnormally low (below LLN) serum Vitamin B12 levels (if subject is taking Vitamin B12
injections, level should be at or above the LLN)
10. Subjects at risk of increased risk of infection, specifically:
• Subjects with chronic viral hepatitis, a history of active tuberculosis disease (TB),
ophthalmic shingles or ocular herpes simplex virus (HSV) infection
• Any active infection within the last 4 weeks before randomization. For such cases, the
timing of randomization can be extended (up to 4 weeks) to allow the infection to resolve
• Any immunological disease which is not adequately controlled, or which requires treatment
with biologic drugs during the study. History of immunoglobulin (Ig) deficiency or other
immunodeficiency disorders (including subjects known to be HIV positive)
11. Have received any live/live attenuated vaccine in the 3 months before randomization
12. Any chronic inflammatory disease that is not adequately controlled or that requires systemic or
ocular immunosuppressive or immunomodulatory therapy.
NOTE: The following subjects do not need to be excluded:
• Subjects with seasonal or perennial allergic rhinitis, asthma, or chronic obstructive
pulmonary disease where the condition is considered to be stable and adequately controlled
by inhaled steroids.
• Hashimoto’s thyroiditis but who are stable on thyroid replacement therapy and not on
systemic immunosuppressive therapy.
• Cutaneous manifestations of immunological disease that do not require systemic
immunosuppressive therapy or systemic immunomodulatory therapy (ie, topical steroid
treatment is permitted)
13. Any other clinically significant abnormalities, such as:
• Physical examination, vital signs, laboratory tests or ECG at Screening or Baseline which
in the opinion of the investigator require further investigation or treatment or which may
interfere with study procedures or safety.
• Other medical conditions (eg, cardiac, respiratory, gastrointestinal, psychiatric, renal
disease) which are not adequately and stably controlled, or which in the opinion of the
investigator(s) could affect the subject’s safety or interfere with the study assessments
(revised per Amendment 01)
• Illiteracy, or severe visual or hearing impairment that would prevent the subject from
performing psychometric tests accurately
14. A prolonged QTc interval calculated using Fridericia’s formula (QTcF) interval (QTcF greater
than 450 ms). If the QTcF is greater than 450 ms on the first single 12-lead ECG, 2 additional
12-lead ECGs will be performed 1 minute apart and the mean of the 3 QTcF values will be
calculated.
15. Malignant neoplasms within 5 years of Screening (except for basal or squamous cell carcinoma in
situ of the skin, or localized prostate cancer in male subjects with treatment cycles completed at
least 6 months prior to screening). Subjects who had malignant neoplasms but who have had at
least 5 years of documented uninterrupted remission before Screening need not be excluded.
16. Hypopigmentation conditions (eg, albinism and vitiligo). Hypopigmentation associated with
scarring need not be exclusionary
17. Known or suspected history of drug or alcohol abuse or dependence within 2 years before
Screening
18. Taking prohibited medications
19. Have participated in a clinical study involving:
• any therapeutic monoclonal antibody, protein derived from a monoclonal antibody,
immunoglobulin therapy, or vaccine within 6 months before Screening for whom it cannot
be documented that they were randomized only to placebo or never received study drug
• elenbecestat (E2609)
• any new chemical entity for AD with last study drug dose occurring within 6 months prior to
Screening unless it can be documented that the subject received only placebo
• any other investigational medication (unless it can be documented that the subject received
only placebo) or device within 8 weeks or 5 half-lives (whichever is longer) before
randomization
20. Planned surgery which requires general, spinal or epidural anesthesia that would take place
during the study. Planned surgery which requires only local anesthesia and which can be
undertaken as day case without inpatient stay postoperatively need not result in exclusion if in the
opinion of the investigator this operation does not interfere with study procedures and subject
safety.
The Estimated Number of Participants
-
Taiwan
40 participants
-
Global
1330 participants
