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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03036280
• Date of registration: 26/01/2017
• Prospective Registration: No
• Primary sponsor: Eisai Co., Ltd.
• Public title: A 24-Month Study to Evaluate the Efficacy and Safety of Elenbecestat (E2609) in Subjects With Early Alzheimer's Disease_ MissionAD2
• Scientific title: A Placebo-Controlled, Double-Blind, Parallel-Group, 24-Month Study With an Open-Label Extension Phase to Evaluate the Efficacy and Safety of Elenbecestat (E2609) in Subjects With Early Alzheimer's Disease
• Date of first enrolment: December 29, 2016
• Target sample size: 1018
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/show/NCT03036280
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

Canada, Chile, China, Croatia, Czech Republic, Czechia, Denmark, Finland, France, Germany, Hungary, Israel, Italy, Japan, Korea, Republic of, Mexico, Poland, Portugal, Singapore, Slovakia, South Africa, Spain, Taiwan, United Kingdom, United States

Key inclusion & exclusion criteria

Inclusion Criteria:

Core Study

- Mild cognitive impairment due to AD or mild AD dementia including

1. MMSE score equal to or greater than 24

2. 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 PET or
CSF AD assessment or both

Extension Phase

•Participants who complete the Core Study

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 (e.g., 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 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 (eg,
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 (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.



Age minimum: 50 Years
Age maximum: 85 Years
Gender: All

Health Condition(s) or Problem(s) studied

Alzheimer's Disease

Intervention(s)

Drug: Elenbecestat (E2609)

Drug: Placebo

Primary Outcome(s)

Open-Label Extension Phase: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings [Time Frame: Month 1, Month 4, Month 12, Month 24 of Extension Phase]

Open-Label Extension Phase: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) [Time Frame: Up to Month 24 of Extension Phase]

Open-Label Extension Phase: Number of Participants With Abnormal Magnetic Resonance Imaging (MRI) Findings [Time Frame: Month 12, Month 24 of Extension Phase]

Open-Label Extension Phase: Number of Participants With Abnormal Neurological Examination Findings [Time Frame: Month 12, Month 24 of Extension Phase]

Open-Label Extension Phase: Number of Participants With Abnormal Physical Examination Findings [Time Frame: Up to Month 24 of Extension Phase]

Core Study: Change From Baseline in the Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score at 24 Months [Time Frame: Baseline, Month 24]

Open-Label Extension Phase: Number of Events of Possible Signals of Drug Abuse Potential [Time Frame: Up to Month 24 of Extension Phase]

Open-Label Extension Phase: Number of Participants With Abnormal Clinically Significant Vital Signs Values [Time Frame: Up to Month 24 of Extension Phase]

Open-Label Extension Phase: Number of Participants With Abnormal Laboratory Safety Test Values [Time Frame: Up to Month 24 of Extension Phase]

Open-Label Extension Phase: Number of Participants With Treatment-Emergent Adverse Events (AEs) [Time Frame: Up to Month 24 of Extension Phase]

Secondary Outcome(s)

Core Study: Change From Baseline in Alzheimer's Disease Composite Score (ADCOMS) at 24 Months [Time Frame: Baseline, Month 24]

Open-Label Extension Phase: Change From Core Study Baseline in ADAS-cog14 Word List (Immediate Recall and Delayed Recall) at Months 12, 24 [Time Frame: Baseline, Month 12, Month 24 of Extension Phase]

Open-Label Extension Phase: Change From Core Study Baseline in ADCOMS at Month 24 [Time Frame: Baseline, Month 24 of Extension Phase]

Open-Label Extension Phase: Change From Core Study Baseline in Mini Mental State Examination (MMSE) at Months 4, 8, 12, 16, 20, 24 [Time Frame: Baseline, Months 4, 8,12,16, 20, and 24 of Extension Phase]

Open-Label Extension Phase: Change From Core Study Baseline in CDR-SB at Months 12, 24 [Time Frame: Baseline, Month 12, Month 24 of Extension Phase]

Core Study: Change From Baseline in Amyloid Positron Emission Tomography Standardized Uptake Value Ratio (PET SUVR) at 24 Months for Brain Amyloid Levels [Time Frame: Baseline, Month 24]

Open-Label Extension Phase: Change From Core Study Baseline in Alzheimer's Disease Assessment Scale-Cognition14 (ADAS-cog14) at Months 12, 24 [Time Frame: Baseline, Month 12, Month 24 of Extension Phase]

Open-Label Extension Phase: Time to Conversion to Dementia for Participants who were not Clinically Staged as Dementia at Core Study Baseline Based on Clinical Diagnosis [Time Frame: Up to 24 months of Extension Phase]

Open-Label Extension Phase: Change From Core Study Baseline in Functional Assessment Questionnaire (FAQ) at Months 4, 8,12,16,20, 24 [Time Frame: Baseline, Months 4, 8,12,16, 20, and 24 of Extension Phase]

Secondary ID(s)

2016-004128-42

E2609-G000-302

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Biogen