Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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. )

Tracking Information
First Submitted Date  ICMJE January 26, 2017
First Posted Date  ICMJE January 30, 2017
Last Update Posted Date September 19, 2019
Actual Study Start Date  ICMJE December 29, 2016
Estimated Primary Completion Date November 21, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 5, 2019)
  • 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 Participants With Treatment-Emergent Adverse Events (AEs) [ 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 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 Abnormal Physical Examination Findings [ Time Frame: Up to 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 Laboratory Safety Test Values [ Time Frame: Up to 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 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 Magnetic Resonance Imaging (MRI) Findings [ Time Frame: Month 12, Month 24 of Extension Phase ]
Original Primary Outcome Measures  ICMJE
 (submitted: January 26, 2017)
Change from Baseline in the Clinical Dementia Rating - Sum of Boxes (CDR-SB) score at 24 months [ Time Frame: Baseline; 24 months ]
Change History Complete list of historical versions of study NCT03036280 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 5, 2019)
  • Core Study: Change From Baseline in Alzheimer's Disease Composite Score (ADCOMS) at 24 Months [ Time Frame: Baseline, Month 24 ]
  • 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 CDR-SB 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 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 ]
  • 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: 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: 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: January 26, 2017)
  • Time to worsening of Clinical Dementia Rating (CDR) score by 24 months [ Time Frame: up to 24 months ]
    Worsening of the global CDR score is defined as an increase from baseline by at least 0.5 points on the global CDR scale on two consecutive scheduled visits at which global CDR is undertaken.
  • Time to conversion to dementia for participants who were not clinically staged as dementia at baseline based on clinical diagnosis [ Time Frame: up to 24 months ]
  • The rate of change over time (mean slope) based on the CDR-SB score over 24 months [ Time Frame: 24 months ]
  • Change from Baseline in CDR-SB at 27 months [ Time Frame: Baseline; 27 months (24 months of treatment plus 3 months posttreatment follow up) ]
  • Change from Baseline in the Alzheimer's Disease Assessment Scale-Cognition14 (ADAS-Cog14) score at 24 months [ Time Frame: Baseline; 24 months ]
  • Change from Baseline in the Mini Mental State Examination (MMSE) score at 24 months [ Time Frame: Baseline; 24 months ]
  • Change from Baseline in the Functional Assessment Questionnaire (FAQ) score at 24 months [ Time Frame: Baseline; 24 months ]
  • Change from Baseline in ADAS-cog14 Word List (immediate recall and delayed recall) scores at 24 months [ Time Frame: Baseline; 24 months ]
Current Other Pre-specified Outcome Measures
 (submitted: June 5, 2019)
  • Core Study: Change From Baseline in CDR-SB at 24 Months for Participants Enriched by Baseline PET SUVR [ Time Frame: Baseline, Month 24 ]
  • Core Study: Change From Baseline in the ADCOMS at 24 Months for Participants Enriched by Baseline PET SUVR [ Time Frame: Baseline, Month 24 ]
  • Core Study: The Rate of Change Over Time (Mean Slope) Based on the CDR-SB Score Over 24 Months [ Time Frame: Baseline, Month 24 ]
  • Core Study: Time to Worsening of Clinical Dementia Rating (CDR) Score by 24 Months [ Time Frame: Baseline, Month 24 ]
  • 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 ]
  • 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) ]
  • Core Study: Change From Baseline in the ADAS-Cog14 Score at 24 Months [ Time Frame: Baseline, Month 24 ]
  • Core Study: Change From Baseline in the MMSE Score at 24 Months [ Time Frame: Baseline, Month 24 ]
  • Core Study: Change From Baseline in the FAQ Score at 24 Months [ Time Frame: Baseline, Month 24 ]
  • 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 ]
Original Other Pre-specified Outcome Measures
 (submitted: January 26, 2017)
  • Change from Baseline in amyloid positron emission tomography standardized uptake value ratio (PET SUVR) composite at 24 months for brain amyloid levels [ Time Frame: Baseline; 24 months ]
  • Change from Baseline in cerebrospinal fluid (CSF) biomarkers t-tau and p-tau at 24 months [ Time Frame: Baseline; 24 months ]
  • Change from Baseline in CSF amyloid biomarkers Aβ(1-40), Aβ(1-42), and Aβ(1-x) at 24 months [ Time Frame: Baseline; 24 months ]
  • Change from Baseline in total hippocampal volume at 24 months using volumetric magnetic resonance imaging (vMRI) [ Time Frame: Baseline; 24 months ]
  • Change from Baseline in the preservation of connectivity on functional MRI (fMRI) at 24 months [ Time Frame: Baseline; 24 months ]
 
Descriptive Information
Brief Title  ICMJE A 24-Month Study to Evaluate the Efficacy and Safety of Elenbecestat (E2609) in Subjects With Early Alzheimer's Disease_
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Alzheimer's Disease
Intervention  ICMJE
  • Drug: Elenbecestat (E2609)
    tablet
    Other Name: Elenbecestat
  • Drug: Placebo
    tablet
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Elenbecestat (E2609)
  • 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.
    Intervention: Drug: Placebo
  • 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.
    Intervention: Drug: Elenbecestat (E2609)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: July 3, 2019)
950
Original Estimated Enrollment  ICMJE
 (submitted: January 26, 2017)
1330
Estimated Study Completion Date  ICMJE November 21, 2023
Estimated Primary Completion Date November 21, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 50 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Chile,   China,   Croatia,   Czechia,   Denmark,   Finland,   France,   Germany,   Hungary,   Italy,   Japan,   Korea, Republic of,   Mexico,   Poland,   Portugal,   Singapore,   Slovakia,   South Africa,   Spain,   Taiwan,   United Kingdom,   United States
Removed Location Countries Czech Republic,   Israel
 
Administrative Information
NCT Number  ICMJE NCT03036280
Other Study ID Numbers  ICMJE E2609-G000-302
2016-004128-42 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Eisai Inc. ( Eisai Co., Ltd. )
Study Sponsor  ICMJE Eisai Co., Ltd.
Collaborators  ICMJE Biogen
Investigators  ICMJE Not Provided
PRS Account Eisai Inc.
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP