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

Alzheimer's Disease Clinical Trial

— MissionAD2  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03036280
• Other study ID #: E2609-G000-302
• Secondary ID: 2016-004128-42
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 29, 2016
• Est. completion date: November 21, 2023

Study information

• Verified date: September 2019
• Source: Eisai Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1018
• Est. completion date: November 21, 2023
• Est. primary completion date: November 21, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

Drug:
• Elenbecestat (E2609)
tablet
• Placebo
tablet
• Elenbecestat (E2609)
tablet

Locations

Country	Name	City	State
Canada	Facility #1	Gatineau	Quebec
Canada	Facility #1	Greenfield Park	Quebec
Canada	Facility #1	Sherbrooke	Quebec
Canada	Facility #1	Toronto	Ontario
Canada	Facility #1	Verdun	Quebec
Chile	Facility #1	Antofagasta
Chile	Facility #1	Santiago	Metropolitan Region
Chile	Facility #2	Santiago	Metropolitan Region
Chile	Facility #3	Santiago	Metropolitan Region
Chile	Facility #4	Santiago	Metropolitan Region
China	Facility #1	Beijing	Beijing
China	Facility #2	Beijing	Beijing
China	Facility #3	Beijing	Beijing
China	Facility #4	Beijing	Beijing
China	Facility #6	Beijing	Beijing
China	Facility #7	Beijing	Beijing
China	Facility #8	Beijing	Beijing
China	Facility #1	Changchun	Jilin
China	Facility #1	Chengdu	Sichuan
China	Facility #1	Chongqing	Chongqing
China	Facility #1	Fuzhou	Fujian
China	Facility #1	Guangzhou	Guangdong
China	Facility #2	Guangzhou	Guangdong
China	Facility #3	Guangzhou	Guangdong
China	Facility #4	Guangzhou	Guangdong
China	Facility #5	Guangzhou	Guangdong
China	Facility #1	Hangzhou	Zheijang
China	Facility #2	Hangzhou	Zheijang
China	Facility #1	Shanghai
China	Facility #2	Shanghai	Shanghai
China	Facility #3	Shanghai	Shanghai
China	Facility #4	Shanghai	Shanghai
China	Facility #1	Shenzhen	Guangdong
China	Facility #1	Taiyuan	Shanxi
China	Facility #1	Tianjin	Tianjin
China	Facility #1	Xi'an	Shanxi
China	Facility #1	Xi'ning City	Qinghai
China	Facility #1	Zhengzhou	Henan
Croatia	Facility #1	Zagreb
Croatia	Facility #2	Zagreb
Croatia	Facility #3	Zagreb
Croatia	Facility #4	Zagreb
Czechia	Facility #1	Brno
Czechia	Facility #2	Brno
Czechia	Facility #1	Praha 10
Czechia	Facility #1	Praha 6
Czechia	Facility #1	Rychnov nad Kneznou
Denmark	Facility #1	Aalborg
Denmark	Facility #1	Ballerup	Copenhagen
Denmark	Facility #1	Vejle	Region Sonerjylland
Finland	Facility #1	Helsinki
Finland	Facility #1	Kuopio
Finland	Facility #1	Oulu
Finland	Facility #1	Turku
France	Facility #1	Limoges
France	Facility #1	Nice
France	Facility #1	Paris
France	Facility #1	Rouen
France	Facility #1	TOURS Cedex
France	Facility #1	Vienne
France	Facility #1	Villefranche-sur-Saône
France	Facility #1	Villeurbanne
Germany	Facility #1	Freiburg
Germany	Facility #1	Hamburg
Germany	Facility #1	Koeln	Deutschland
Germany	Facility #1	Mannheim	Baden Wurttemberg
Germany	Facility #1	Mittweida	Saxony
Germany	Facility #1	Muenchen	Bavaria
Germany	Facility #1	Munchen	Bayern
Germany	Facility #1	Schwerin	Mecklenburg Vorpommern
Germany	Facility #1	Siegen	North Rhine-Westphalia
Germany	Facility #1	Ulm
Hungary	Facility #1	Budapest
Hungary	Facility #2	Budapest
Hungary	Facility #1	Komarom	Esztergom
Italy	Facility #1	Ancona
Italy	Facility #2	Brescia
Italy	Facility #1	Cefalu	Palermo
Italy	Facility #1	Chieti
Italy	Facility #2	Milano
Italy	Facility #3	Milano
Italy	Facility #1	Orbassano
Italy	Facility #1	Pisa
Italy	Facility #1	Pozzilli
Italy	Facility #1	Roma
Italy	Facility #1	Rome
Italy	Facility #2	Rome
Italy	Facility #1	Salerno
Italy	Facility #1	Torino
Italy	Facility #2	Verona
Japan	Eisai Trial Site 1	Atsugi-shi	Kanagawa
Japan	Eisai Trial Site 1	Bunkyo-ku	Tokyo
Japan	Eisai Trial Site 2	Bunkyo-ku	Tokyo
Japan	Eisai Trial Site 3	Bunkyo-ku	Tokyo
Japan	Eisai Trial Site 4	Bunkyo-ku	Tokyo
Japan	Eisai Trial Site 1	Chiba-shi	Chiba
Japan	Eisai Trial Site 2	Chiba-shi	Chiba
Japan	Eisai Trial Site 1	Chuo-ku	Niigata-city/Niigata
Japan	Eisai Trial Site 1	Fujisawa-shi	Kanagawa
Japan	Eisai Trial Site 1	Hachioji	Tokyo
Japan	Eisai Trial Site 1	Hirosaki-city	Aomori
Japan	Eisai Trial Site 1	Inzai	Chiba
Japan	Eisai Trial Site 1	Iruma-gun	Saitama
Japan	Eisai Trial Site 1	Isezaki-city	Gunma
Japan	Eisai Trial Site 1	Kamakura-shi	Kanagawa
Japan	Eisai Trial Site 1	Kanazawa-shi	Ishikawa
Japan	Eisai Trial Site 1	Kasukabe City	Saitama
Japan	Eisai Trial Site 1	Katsushika-ku	Tokyo
Japan	Eisai Trial Site 1	Kawasaki-shi	Kanagawa
Japan	Eisai Trial Site 1	Koriyama	Fukushima
Japan	Eisai Trial Site 1	Koshigaya-shi	Saitama
Japan	Eisai Trial Site 2	Koshigaya-shi	Saitama
Japan	Eisai Trial Site 1	Koto-ku	Tokyo
Japan	Eisai Trial Site 1	Maebashi city	Gunma
Japan	Eisai Trial Site 1	Minato-ku	Tokyo
Japan	Eisai Trial Site 1	Minato-ku	Tokyo
Japan	Eisai Trial Site 1	Mitaka City	Tokyo
Japan	Eisai Trial Site 1	Morioka-shi	Iwate
Japan	Eisai Trial Site 1	Nagaoka	Niigata
Japan	Eisai Trial Site 1	Nagoya	Aichi
Japan	Eisai Trial Site 1	Nerima-ku	Tokyo
Japan	Eisai Trial Site 1	Ota-ku	Tokyo
Japan	Eisai Trial Site 2	Ota-ku	Tokyo
Japan	Eisai Trial Site 1	Saitama city	Saitama
Japan	Eisai Trial Site 1	Sapporo	Hokkaido
Japan	Eisai Trial Site 2	Sapporo-shi	Hokkaido
Japan	Eisai Trial Site 3	Sapporo-shi	Hokkaido
Japan	Eisai Trial Site 1	Shibuya-ku	Tokyo
Japan	Eisai Trial Site 1	Shinagawa-ku	Tokyo
Japan	Eisai Trial Site 2	Shinagawa-ku	Tokyo
Japan	Eisai Trial Site 1	Shinjuku-ku	Tokyo
Japan	Eisai Trial Site 2	Shinjuku-ku	Tokyo
Japan	Eisai Trial Site 1	Shizuoka-city	Shizuoka
Japan	Eisai Trial Site 1	Toride	Ibaraki
Japan	Eisai Trial Site 1	Urayasu	Chiba
Japan	Eisai Trial Site 1	Yokohama	Kanagawa
Japan	Eisai Trial Site 2	Yokohama	Kanagawa
Korea, Republic of	Facility #1	Gwangju-si
Korea, Republic of	Facility #1	Incheon
Korea, Republic of	Facility #1	Seongnam	Gyeonggi
Korea, Republic of	Facility #1	Seoul
Korea, Republic of	Facility #2	Seoul
Korea, Republic of	Facility #3	Seoul
Korea, Republic of	Facility #4	Seoul
Korea, Republic of	Facility #5	Seoul
Korea, Republic of	Facility #6	Seoul
Mexico	Facility #1	Guadalajara	Jalisco
Mexico	Facility #1	Mexico City
Mexico	Facility #1	Monterrey	Nuevo Leon
Mexico	Facility #2	Monterrey	Nuevo Leon
Poland	Facility #1	Bialystok
Poland	Facility #1	Bydgoszcz
Poland	Facility #1	Katowice	Silesia
Poland	Facility #1	Krakow
Poland	Facility #2	Krakow
Poland	Facility #1	Pruszcz Gdanski
Poland	Facility #1	Warszawa
Portugal	Facility #1	Braga
Portugal	Facility #1	Guimaräes	Creixomil
Portugal	Facility #1	Matosinhos
Portugal	Facility #1	Santa Maria da Feira
Portugal	Facility #1	Torres Vedras
Singapore	Facility #1	Singapore
Singapore	Facility #2	Singapore
Slovakia	Facility #1	Banska Bystrica
Slovakia	Facility #1	Bratislava
Slovakia	Facility #2	Bratislava
Slovakia	Facility #3	Bratislava
Slovakia	Facility #1	Dubnica nad Vahom
Slovakia	Facility #1	Kosice
Slovakia	Facility #1	Roznava
Slovakia	Facility #1	Svidnik	Slovak Republic
South Africa	Facility #1	Cape Town	Western Cape
South Africa	Facility #2	Cape Town	Western Cape
South Africa	Facility #1	George	Western Cape
South Africa	Facility #1	Johannesburg	Gauteng
South Africa	Facility #1	Pinelands	Cape Town
Spain	Facility #1	Barcelona
Spain	Facility #2	Barcelona	Catalunya
Spain	Facility #3	Barcelona
Spain	Facility #1	Castilla Y Leon	Zamora
Spain	Facility #1	Madrid
Spain	Facility #2	Madrid
Spain	Facility #3	Madrid
Spain	Facility #4	Madrid
Spain	Facility #1	Salamanca
Spain	Facility #1	San Sebastian	Gipuzkoa
Spain	Facility #1	Sevilla
Taiwan	Facility #1	Changhua
Taiwan	Facility #1	Changhua County
Taiwan	Facility #2	Kaohsiung City
Taiwan	Facility #1	New Taipei City
Taiwan	Facility #1	Taichung City
Taiwan	Facility #1	Tainan City
Taiwan	Facility #1	Taipei
Taiwan	Facility #2	Taipei
Taiwan	Facility #1	Taiwan
Taiwan	Facility #1	Taoyuan City
United Kingdom	Facility #1	Birmingham
United Kingdom	Facility #1	Guildford
United States	Facility #1	Albany	New York
United States	Facility #1	Aventura	Florida
United States	Facility #1	Baton Rouge	Louisiana
United States	Facility #1	Beachwood	Ohio
United States	Facility #1	Bellflower	California
United States	Facility #1	Bradenton	Florida
United States	Facility #1	Charlotte	North Carolina
United States	Facility #2	Charlotte	North Carolina
United States	Facility #1	Chicago	Illinois
United States	Facility #1	Creve Coeur	Missouri
United States	Facility #1	Dallas	Texas
United States	Facility #1	Decatur	Georgia
United States	Facility #1	DeSoto	Texas
United States	Facility #1	Doral	Florida
United States	Facility #1	Elk Grove Village	Illinois
United States	Facility #1	Gilbert	Arizona
United States	Facility #1	Glendale	California
United States	Facility #1	Glens Falls	New York
United States	Facility #1	Greenville	Texas
United States	Facility #1	Hattiesburg	Mississippi
United States	Facility #1	Hialeah	Florida
United States	Facility #2	Hialeah	Florida
United States	Facility #1	Honolulu	Hawaii
United States	Facility #1	Houston	Texas
United States	Facility #1	Houston	Texas
United States	Facility #1	Irvine	California
United States	Facility #2	Jacksonville	Florida
United States	Facility #1	Knoxville	Tennessee
United States	Facility #1	Laguna Hills	California
United States	Facility #1	Lake Worth	Florida
United States	Facility #1	Las Vegas	Nevada
United States	Facility #1	Little Rock	Arkansas
United States	Facility #1	Lomita	California
United States	Facility #1	Los Angeles	California
United States	Facility #1	Maitland	Florida
United States	Facility #1	Manhasset	New York
United States	Facility #1	Mansfield	Texas
United States	Facility #1	Medford	Oregon
United States	Facility #1	Melbourne	Florida
United States	Facility #1	Miami	Florida
United States	Facility #2	Miami	Florida
United States	Facility #3	Miami	Florida
United States	Facility #4	Miami	Florida
United States	Facility #5	Miami	Florida
United States	Facility #6	Miami	Florida
United States	Facility #7	Miami	Florida
United States	Facility #8	Miami	Florida
United States	Facility #9	Miami	Florida
United States	Facility #1	Miami Lakes	Florida
United States	Facility #1	Miami Springs	Florida
United States	Facility #1	New Haven	Connecticut
United States	Facility #1	Newnan	Georgia
United States	Facility #1	Norristown	Pennsylvania
United States	Facility #1	North Miami	Florida
United States	Facility #1	Ocala	Florida
United States	Facility #1	Oceanside	California
United States	Facility #1	Oklahoma City	Oklahoma
United States	Facility #1	Orange City	Florida
United States	Facility #1	Ormond Beach	Florida
United States	Facility #1	Palmetto Bay	Florida
United States	Facility #1	Palo Alto	California
United States	Facility #1	Pembroke Pines	Florida
United States	Facility #1	Phoenix	Arizona
United States	Facility #1	Pinellas Park	Florida
United States	Facility #1	Plains	Pennsylvania
United States	Facility #1	Plymouth	Massachusetts
United States	Facility #1	Portland	Oregon
United States	Facility #1	Richmond	Virginia
United States	Facility #2	Richmond	Virginia
United States	Facility #1	Riverside	California
United States	Facility# 1	Saint Louis	Missouri
United States	Facility #1	Saint Petersburg	Florida
United States	Facility #1	Salt Lake City	Utah
United States	Facility #1	Santa Ana	California
United States	Facility #2	Santa Ana	California
United States	Facility #1	Santa Monica	California
United States	Facility #1	Schaumburg	Illinois
United States	Facility #1	Stamford	Connecticut
United States	Facility #1	Toms River	New Jersey
United States	Facility #1	West Jordan	Utah
United States	Facility #1	West Palm Beach	Florida
United States	Facility #1	Wichita	Kansas
United States	Facility #1	Woodmere	New York

Sponsors (2)

Lead Sponsor	Collaborator
Eisai Co., Ltd.	Biogen

Countries where clinical trial is conducted

United States,  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, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Core Study: Change From Baseline in CDR-SB at 24 Months for Participants Enriched by Baseline PET SUVR		Baseline, Month 24
Other	Core Study: Change From Baseline in the ADCOMS at 24 Months for Participants Enriched by Baseline PET SUVR		Baseline, Month 24
Other	Core Study: The Rate of Change Over Time (Mean Slope) Based on the CDR-SB Score Over 24 Months		Baseline, Month 24
Other	Core Study: Time to Worsening of Clinical Dementia Rating (CDR) Score by 24 Months		Baseline, Month 24
Other	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		Baseline, Month 24
Other	Core Study: Change From Baseline in CDR-SB at 27 Months		Baseline, Month 27 (24 months of treatment plus 3 months post treatment follow up)
Other	Core Study: Change From Baseline in the ADAS-Cog14 Score at 24 Months		Baseline, Month 24
Other	Core Study: Change From Baseline in the MMSE Score at 24 Months		Baseline, Month 24
Other	Core Study: Change From Baseline in the FAQ Score at 24 Months		Baseline, Month 24
Other	Core Study: Change From Baseline in the ADAS-cog14 Word List (Immediate Recall and Delayed Recall) Score at 24 Months		Baseline, Month 24
Primary	Core Study: Change From Baseline in the Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score at 24 Months		Baseline, Month 24
Primary	Open-Label Extension Phase: Number of Participants With Treatment-Emergent Adverse Events (AEs)		Up to Month 24 of Extension Phase
Primary	Open-Label Extension Phase: Number of Participants With Abnormal Clinically Significant Vital Signs Values		Up to Month 24 of Extension Phase
Primary	Open-Label Extension Phase: Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings		Month 1, Month 4, Month 12, Month 24 of Extension Phase
Primary	Open-Label Extension Phase: Number of Participants With Abnormal Physical Examination Findings		Up to Month 24 of Extension Phase
Primary	Open-Label Extension Phase: Number of Participants With Abnormal Neurological Examination Findings		Month 12, Month 24 of Extension Phase
Primary	Open-Label Extension Phase: Number of Participants With Abnormal Laboratory Safety Test Values		Up to Month 24 of Extension Phase
Primary	Open-Label Extension Phase: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS)		Up to Month 24 of Extension Phase
Primary	Open-Label Extension Phase: Number of Events of Possible Signals of Drug Abuse Potential		Up to Month 24 of Extension Phase
Primary	Open-Label Extension Phase: Number of Participants With Abnormal Magnetic Resonance Imaging (MRI) Findings		Month 12, Month 24 of Extension Phase
Secondary	Core Study: Change From Baseline in Alzheimer's Disease Composite Score (ADCOMS) at 24 Months		Baseline, Month 24
Secondary	Core Study: Change From Baseline in Amyloid Positron Emission Tomography Standardized Uptake Value Ratio (PET SUVR) at 24 Months for Brain Amyloid Levels		Baseline, Month 24
Secondary	Open-Label Extension Phase: Change From Core Study Baseline in CDR-SB at Months 12, 24		Baseline, Month 12, Month 24 of Extension Phase
Secondary	Open-Label Extension Phase: Change From Core Study Baseline in ADCOMS at Month 24		Baseline, Month 24 of Extension Phase
Secondary	Open-Label Extension Phase: Change From Core Study Baseline in Mini Mental State Examination (MMSE) at Months 4, 8, 12, 16, 20, 24		Baseline, Months 4, 8,12,16, 20, and 24 of Extension Phase
Secondary	Open-Label Extension Phase: Change From Core Study Baseline in Functional Assessment Questionnaire (FAQ) at Months 4, 8,12,16,20, 24		Baseline, Months 4, 8,12,16, 20, and 24 of Extension Phase
Secondary	Open-Label Extension Phase: Change From Core Study Baseline in Alzheimer's Disease Assessment Scale-Cognition14 (ADAS-cog14) at Months 12, 24		Baseline, Month 12, Month 24 of Extension Phase
Secondary	Open-Label Extension Phase: Change From Core Study Baseline in ADAS-cog14 Word List (Immediate Recall and Delayed Recall) at Months 12, 24		Baseline, Month 12, Month 24 of Extension Phase
Secondary	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		Up to 24 months of Extension Phase