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A 24-Month Study to Evaluate the Efficacy and Safety of Elenbecestat (E2609) in Subjects With Early Alzheimer's Disease_ (MissionAD2)

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ClinicalTrials.gov Identifier: NCT03036280
Recruitment Status : Active, not recruiting
First Posted : January 30, 2017
Last Update Posted : September 19, 2019
Sponsor:
Collaborator:
Biogen
Information provided by (Responsible Party):
Eisai Inc. ( Eisai Co., Ltd. )

Brief Summary:
The name of this trial is MissionAD2. 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 end points for the studies E2609-G000-301 (NCT02956486) and E2609-G000-302 (NCT03036280) will be pooled for a combined total of 1900 participants.

Condition or disease Intervention/treatment Phase
Alzheimer's Disease Drug: Elenbecestat (E2609) Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 950 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : December 29, 2016
Estimated Primary Completion Date : November 21, 2023
Estimated Study Completion Date : November 21, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Core Study: Elenbecestat (E2609) 50 mg
Participants will receive one 50 milligram (mg) elenbecestat (E2609) tablet orally once a day in the morning. The core study will be double blinded.
Drug: Elenbecestat (E2609)
tablet
Other Name: 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
tablet

Experimental: Open Label Extension Phase: Elenbecestat (E2609) 50 mg
Participants completing the core study will receive one 50 milligram (mg) elenbecestat (E2609) tablet orally once a day in the morning.
Drug: Elenbecestat (E2609)
tablet
Other Name: Elenbecestat




Primary Outcome Measures :
  1. Core Study: Change From Baseline in the Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score at 24 Months [ Time Frame: Baseline, Month 24 ]
  2. Open-Label Extension Phase: Number of Participants With Treatment-Emergent Adverse Events (AEs) [ Time Frame: Up to Month 24 of Extension Phase ]
  3. Open-Label Extension Phase: Number of Participants With Abnormal Clinically Significant Vital Signs Values [ Time Frame: Up to Month 24 of Extension Phase ]
  4. 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 ]
  5. Open-Label Extension Phase: Number of Participants With Abnormal Physical Examination Findings [ Time Frame: Up to Month 24 of Extension Phase ]
  6. Open-Label Extension Phase: Number of Participants With Abnormal Neurological Examination Findings [ Time Frame: Month 12, Month 24 of Extension Phase ]
  7. Open-Label Extension Phase: Number of Participants With Abnormal Laboratory Safety Test Values [ Time Frame: Up to Month 24 of Extension Phase ]
  8. 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 ]
  9. Open-Label Extension Phase: Number of Events of Possible Signals of Drug Abuse Potential [ Time Frame: Up to Month 24 of Extension Phase ]
  10. Open-Label Extension Phase: Number of Participants With Abnormal Magnetic Resonance Imaging (MRI) Findings [ Time Frame: Month 12, Month 24 of Extension Phase ]

Secondary Outcome Measures :
  1. Core Study: Change From Baseline in Alzheimer's Disease Composite Score (ADCOMS) at 24 Months [ Time Frame: Baseline, Month 24 ]
  2. 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 ]
  3. 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 ]
  4. Open-Label Extension Phase: Change From Core Study Baseline in ADCOMS at Month 24 [ Time Frame: Baseline, Month 24 of Extension Phase ]
  5. 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 ]
  6. 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 ]
  7. 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 ]
  8. 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 ]
  9. 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 ]

Other Outcome Measures:
  1. Core Study: Change From Baseline in CDR-SB at 24 Months for Participants Enriched by Baseline PET SUVR [ Time Frame: Baseline, Month 24 ]
  2. Core Study: Change From Baseline in the ADCOMS at 24 Months for Participants Enriched by Baseline PET SUVR [ Time Frame: Baseline, Month 24 ]
  3. Core Study: The Rate of Change Over Time (Mean Slope) Based on the CDR-SB Score Over 24 Months [ Time Frame: Baseline, Month 24 ]
  4. Core Study: Time to Worsening of Clinical Dementia Rating (CDR) Score by 24 Months [ Time Frame: Baseline, Month 24 ]
  5. Core Study: Time to Conversion to Dementia by 24 Months for Participants who were not Clinically Staged as Dementia at Baseline Based on Clinical Diagnosis [ Time Frame: Baseline, Month 24 ]
  6. Core Study: Change From Baseline in CDR-SB at 27 Months [ Time Frame: Baseline, Month 27 (24 months of treatment plus 3 months post treatment follow up) ]
  7. Core Study: Change From Baseline in the ADAS-Cog14 Score at 24 Months [ Time Frame: Baseline, Month 24 ]
  8. Core Study: Change From Baseline in the MMSE Score at 24 Months [ Time Frame: Baseline, Month 24 ]
  9. Core Study: Change From Baseline in the FAQ Score at 24 Months [ Time Frame: Baseline, Month 24 ]
  10. Core Study: Change From Baseline in the ADAS-cog14 Word List (Immediate Recall and Delayed Recall) Score at 24 Months [ Time Frame: Baseline, Month 24 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   50 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03036280


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Sponsors and Collaborators
Eisai Co., Ltd.
Biogen

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Responsible Party: Eisai Co., Ltd.
ClinicalTrials.gov Identifier: NCT03036280     History of Changes
Other Study ID Numbers: E2609-G000-302
2016-004128-42 ( EudraCT Number )
First Posted: January 30, 2017    Key Record Dates
Last Update Posted: September 19, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Keywords provided by Eisai Inc. ( Eisai Co., Ltd. ):
Elenbecestat
E2609
Alzheimer's Disease
Early Alzheimer's Disease
Prodromal Alzheimer's Disease
Dementia
Dementia, Alzheimer's type
Mild Cognitive Impairment
MissionAD2
Additional relevant MeSH terms:
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Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders