Study Stopped
Study was discontinued based on futility analysis done and not based on safety concerns. Follow-up visits and closing out study activities are completed
221AD301 Phase 3 Study of Aducanumab (BIIB037) in Early Alzheimer's Disease
ENGAGE
A Phase 3 Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Aducanumab (BIIB037) in Subjects With Early Alzheimer's Disease
2 other identifiers
interventional
1,653
13 countries
179
Brief Summary
The primary objective of the study is to evaluate the efficacy of monthly doses of aducanumab in slowing cognitive and functional impairment as measured by changes in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score as compared with placebo in participants with early AD. Secondary objectives are to assess the effect of monthly doses of aducanumab as compared with placebo on clinical progression as measured by Mini-Mental State Examination (MMSE), AD Assessment Scale-Cognitive Subscale (13 items) \[ADAS-Cog 13\], and AD Cooperative Study-Activities of Daily Living Inventory (Mild Cognitive Impairment version) \[ADCS-ADL-MCI\].
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Aug 2015
Typical duration for phase_3
179 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 18, 2015
CompletedFirst Posted
Study publicly available on registry
June 23, 2015
CompletedStudy Start
First participant enrolled
August 13, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 8, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
August 8, 2019
CompletedResults Posted
Study results publicly available
September 2, 2021
CompletedSeptember 2, 2021
August 1, 2021
4 years
June 18, 2015
July 1, 2021
August 9, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SB) Score at Week 78
CDR-SB integrates assessments from 3 domains of cognition (memory, orientation, judgment/problem-solving) and 3 domains of function (community affairs, home/hobbies, personal care). Following caregiver interview and systematic patient examination, the rater assigns a score describing the participant's current performance level in each of these domains of life functioning. Prespecified severity anchors range from none = 0, questionable = 0.5, mild = 1, moderate = 2 to severe = 3 (the personal care domain omits the 0.5 score). "Sum of boxes" scoring methodology sums the score for each of the 6 domains and provides a value ranging from 0 to 18 that can change in increments of 0.5 or greater. Higher scores indicate greater disease severity. Mixed model for repeated measures (MMRM) analysis was used to analyze change from baseline in CDR-SB. A positive change from baseline indicates clinical decline.
Baseline, Week 78
Secondary Outcomes (3)
Change From Baseline in Mini-Mental State Examination (MMSE) Score at Week 78
Baseline, Week 78
Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (13 Items) (ADAS-Cog 13) Score at Week 78
Baseline, Week 78
Change From Baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (Mild Cognitive Impairment Version) (ADCS-ADL-MCI) Score at Week 78
Baseline, Week 78
Study Arms (2)
Low Dose
EXPERIMENTALMonthly intravenous (IV) infusion
High Dose
EXPERIMENTALMonthly intravenous (IV) infusion
Interventions
Eligibility Criteria
You may qualify if:
- Must meet all of the following clinical criteria for MCI due to AD or mild AD and must have:
- A Clinical Dementia Rating (CDR)-Global Score of 0.5.
- Objective evidence of cognitive impairment at screening
- An MMSE score between 24 and 30 (inclusive)
- Must have a positive amyloid Positron Emission Tomography (PET) scan
- Must consent to apolipoprotein E (ApoE) genotyping
- If using drugs to treat symptoms related to AD, doses must be stable for at least 8 weeks prior to screening visit 1
- Must have a reliable informant or caregiver
You may not qualify if:
- Any medical or neurological condition (other than Alzheimer's Disease) that might be a contributing cause of the subject's cognitive impairment
- Have had a stroke or Transient Ischemic Attack (TIA) or unexplained loss of consciousness in the past 1 year
- Clinically significant unstable psychiatric illness in past 6 months
- History of unstable angina, myocardial infarction, advanced chronic heart failure, or clinically significant conduction abnormalities within 1 year prior to Screening
- Indication of impaired renal or liver function
- Have human immunodeficiency virus (HIV) infection
- Have a significant systematic illness or infection in past 30 days
- Relevant brain hemorrhage, bleeding disorder and cerebrovascular abnormalities
- Any contraindications to brain magnetic resonance imaging (MRI) or PET scans
- Alcohol or substance abuse in past 1 year
- Taking blood thinners (except for aspirin at a prophylactic dose or less)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Biogenlead
Study Sites (181)
St. Joseph's Hospital and Medical Center
Phoenix, Arizona, 85013, United States
Center for Neurosciences
Tucson, Arizona, 85718, United States
Neurology Center of North Orange County
Fullerton, California, 92835, United States
Senior Clinical Trials, Inc.
Laguna Hills, California, 92653, United States
Torrance Clinical Research Institute, Inc.
Lomita, California, 90717, United States
University of California - Los Angeles
Los Angeles, California, 90095, United States
UCSF - Memory and Aging Center
San Francisco, California, 94158, United States
California Neuroscience Research Medical Group Inc.
Sherman Oaks, California, 91403, United States
Southern California Research LLC
Simi Valley, California, 93065, United States
Institute for Neurodegenerative Disorders
New Haven, Connecticut, 06510, United States
Georgetown University Hospital
Washington D.C., District of Columbia, 20057, United States
Brain Matters Research, Inc.
Delray Beach, Florida, 33445, United States
Neuropsychiatric Research Center of Southwest Florida
Fort Myers, Florida, 33912, United States
Jacksonville Center for Clinical Research
Jacksonville, Florida, 32216, United States
University of Miami
Miami, Florida, 33136, United States
Miami Jewish Health Systems
Miami, Florida, 33137, United States
Compass Research Main
Orlando, Florida, 32806, United States
Palm Beach Neurological Center
Palm Beach Gardens, Florida, 33410, United States
Stedman Clinical Trials, LLC
Tampa, Florida, 33613, United States
USF Health Byrd Institute
Tampa, Florida, 33616, United States
Meridien Research
Tampa, Florida, 33634, United States
Compass Research Main
The Villages, Florida, 32162, United States
Premiere Research Institute
West Palm Beach, Florida, 33407, United States
Cleveland Clinic Florida - Weston
Weston, Florida, 33331, United States
Alexian Brothers Neurosciences Institute
Elk Grove Village, Illinois, 60007, United States
Advocate Lutheran General Hospital
Park Ridge, Illinois, 60068, United States
Fort Wayne Neurological Center
Fort Wayne, Indiana, 46804, United States
Indiana University School of Medicine
Indianapolis, Indiana, 46202, United States
University of Kansas Medical Center Research Institute, Inc.
Kansas City, Kansas, 66160, United States
Via Christi Research, a division of Via Christi Hospitals Wichita, Inc.
Wichita, Kansas, 67214, United States
Baptist Health Lexington
Lexington, Kentucky, 40503, United States
Brigham & Women's Hosp End/Dbt
Boston, Massachusetts, 02115, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215, United States
ActivMed Practices & Research
Methuen, Massachusetts, 01844, United States
Donald S. Marks, M.D., P.C.
Plymouth, Massachusetts, 02360, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
Washington University
St Louis, Missouri, 63131, United States
Las Vegas Medical research
Las Vegas, Nevada, 89113, United States
Advanced Memory Research Institute of NJ, PC
Toms River, New Jersey, 08755, United States
Albany Medical College
Albany, New York, 12208, United States
New York University Medical Center PRIME
New York, New York, 10016, United States
University of Rochester
Rochester, New York, 14620, United States
ANI Neurology, PLLC d/b/a Alzheimer's Memory Center
Charlotte, North Carolina, 28270, United States
Raleigh Neurology Associates, P.A.
Raleigh, North Carolina, 27607-6010, United States
Cleveland Clinic
Cleveland, Ohio, 44195, United States
Lynn Health Science Institute
Oklahoma City, Oklahoma, 73112, United States
The Clinical Trial Center, LLC
Jenkintown, Pennsylvania, 19046, United States
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213, United States
Northeastern Pennsylvania Memory and Alzheimer's Center
Plains, Pennsylvania, 18705, United States
Rhode Island Mood & Memory Research Institute
East Providence, Rhode Island, 02915, United States
Butler Hospital
Providence, Rhode Island, 02906, United States
Medical University of South Carolina (MUSC)
Charleston, South Carolina, 29425, United States
Neurology Clinic, PC
Cordova, Tennessee, 38108, United States
University of Tennessee Medical Center. Knoxville
Knoxville, Tennessee, 37920, United States
Clinical Neuroscience Solutions, Inc.
Memphis, Tennessee, 38119, United States
UT Southwestern Medical Center at Dallas
Dallas, Texas, 75390, United States
Baylor College of Medicine
Houston, Texas, 77030, United States
National Clinical Research Inc.-Richmond
Richmond, Virginia, 23294, United States
Medical College of Wisconsin, Inc.
Milwaukee, Wisconsin, 53266, United States
St Vincent's Hospital Sydney
Darlinghurst, New South Wales, 2010, Australia
Central Coast Neurosciences Research, Gosford
East Gosford, New South Wales, 2250, Australia
Central Coast Neurosciences Research
Erina, New South Wales, 2250, Australia
KARA Institute for Neurological Diseases
North Ryde, New South Wales, 2113, Australia
Calvary Mater Newcastle
Waratah, New South Wales, 2298, Australia
The Prince Charles Hospital
Chermside, Queensland, 4032, Australia
Royal Brisbane and Women's Hospital
Herston, Queensland, 4006, Australia
Toowoomba Base Hospital
Toowoomba, Queensland, 4350, Australia
Box Hill Hospital
Box Hill, Victoria, 3128, Australia
Austin Hospital
Heidelberg, Victoria, 3084, Australia
Royal Melbourne Hospital
Parkville, Victoria, 3050, Australia
Neurodegenerative Disorders Research
West Perth, Western Australia, 6005, Australia
LKH - Universitaetsklinikum Graz
Graz, 8036, Austria
Christian-Doppler-Klinik - Universitätsklinikum Salzburg
Salzburg, 5020, Austria
Heritage Medical Research Clinic
Calgary, Alberta, T2N 1N4, Canada
The Medical Arts Health Research Group
Penticton, British Columbia, V2A 5C8, Canada
UBC Hospital
Vancouver, British Columbia, V6T 2B5, Canada
Toronto Memory Program (Neurology Research Inc.)
Toronto, Ontario, M3B 2S7, Canada
Toronto Sunnybrook Hospital
Toronto, Ontario, M4N 3M5, Canada
The Montreal Neurological Institute
Montreal, Quebec, H3A 2B4, Canada
McGill Centre for Studies in Aging
Verdun, Quebec, H4H 1R3, Canada
CHU de Quebec - Hôpital de l' Enfant Jésus
Québec, G1J 1Z4, Canada
CCBR - Ålborg - DK
Aalborg, 9100, Denmark
CCBR - Ballerup - DK
Ballerup Municipality, 2750, Denmark
Rigshospitalet
København Ø, 2100, Denmark
CCBR - Vejle - DK
Vejle, 7100, Denmark
Hopital Louis Pasteur Colmar
Strasbourg, Bas Rhin, 67091, France
CHU Strasbourg - Hôpital Hautepierre
Strasbourg, Bas Rhin, 67098, France
Groupe Hospitalier Pellegrin - Hôpital Pellegrin
Bordeaux, Gironde, 33076, France
CHU Reims - Hôpital Maison Blanche
Reims, Marne, 51092, France
Hopital Neurologique Pierre Wertheimer
Bron, Rhone, 69677, France
Groupe hospitalier Broca - La Rochefoucauld - La Collégiale
Paris, 75013, France
Groupe Hospitalier Pitie-Salpetriere
Paris, 75013, France
Praxis Dr. Scholz
Böblingen, Baden-Wurttemberg, 71034, Germany
Aerztliche Gemeinschaftspraxis
Ostfildern, Baden-Wurttemberg, 73760, Germany
Neuro MVZ Stuttgart
Stuttgart, Baden-Wurttemberg, 70182, Germany
Klinikum der Johann Wolfgang Goethe-Universitaet
Frankfurt, Bavaria, 97080, Germany
Praxis Dr. med. Bergmann
Neuburg am Inn, Bavaria, 86633, Germany
Neurologische Gemeinschaftspraxis Kassel
Kassel, Hesse, 34121, Germany
Klinische Forschung Hannover-Mitte GmbH
Hanover, Lower Saxony, 30159, Germany
Universitaetsklinikum Aachen AOeR
Aachen, North Rhine-Westphalia, 52074, Germany
Universitaetsklinikum Bonn AoeR
Bonn, North Rhine-Westphalia, 53127, Germany
Universitaetsklinikum Koeln
Cologne, North Rhine-Westphalia, 53105, Germany
Charite Universitaetsmedizin Berlin - Campus Benjamin Franklin
Berlin, 14050, Germany
Azienda Ospedaliero Universitaria Ospedali Riuniti
Torrette Di Ancona, Ancona, 60126, Italy
Fondazione Istituto G.Giglio di Cefalù
Cefalù, Palermo, 90015, Italy
Azienda Ospedaliera Ospedali Riuniti di Bergamo
Bergamo, 24100, Italy
Azienda Ospedaliera Spedali Civili di Brescia
Brescia, 25100, Italy
Azienda Ospedaliero Universitaria San Martino
Genova, 16132, Italy
Ospedale San Raffaele
Milan, 20132, Italy
Casa di Cura del Policlinico
Milan, 20144, Italy
Azienda Ospedaliera Universitaria "Federico II"
Napoli, 80131, Italy
Seconda Università degli Studi di Napoli
Napoli, 80138, Italy
Azienda Ospedaliero Universitaria Pisana
Pisa, 56126, Italy
Policlinico Universitario Agostino Gemelli
Roma, 00168, Italy
Azienda Ospedaliera Universitaria OO. RR. S. Giovanni di Dio e Ruggi D'Aragona
Salerno, 84131, Italy
A.O.U. Senese Policlinico Santa Maria alle Scotte
Siena, 53100, Italy
Research Site
Chiba, Chiba, 263-0043, Japan
Research Site
Inzai-shi, Chiba, Japan
Research Site
Kurume-shi, Fukuoka, 830-0011, Japan
Research Site
Aizuwakamatsu-shi, Fukushima, 965-8585, Japan
Research Site
Asahikawa-shi, Hokkaido, 070-8644, Japan
Research Site
Sapporo, Hokkaido, 006-8555, Japan
Research Site
Sapporo, Hokkaido, 064-8570, Japan
Research Site
Atsugi-shi, Kanagawa, 243-8551, Japan
Research Site
Kamakura-shi, Kanagawa, 247-8533, Japan
Research Site
Kawasaki-Shi, Kanagawa, 211-8533, Japan
Unknown Facility
Yokohama, Kanagawa, 223-0059, Japan
Research Site
Yokohama, Kanagawa, 225-0013, Japan
Research Site
Yokohama, Kanagawa, 225-0025, Japan
Research Site
Kyoto, Kyoto, 616-8255, Japan
Research Site
Nagaoka-shi, Niigata, 940-2081, Japan
Research Site
Iruma-gun, Saitama, 350-0495, Japan
Research Site
Kasukabe-shi, Saitama, 344-0036, Japan
Research Site
Ōta-ku, Tokyo, 143-8541, Japan
Research Site
Bunkyō City, Tokyo-To, 113-0034, Japan
Research Site
Shinjuku-ku (I), Tokyo-To, 162-8655, Japan
Research Site
Shinjuku-ku, Tokyo-To, 162-8655, Japan
Research Site
Yamagata, Yamagata, 990-0834, Japan
Research Site
Itabashi-ku, 173-0015, Japan
Research Site
Itabashi-ku, 173-8610, Japan
Research Site
Kiyose-shi, Japan
Research Site
Kodaira-shi, 187-8551, Japan
Hospital Professor Doutor Fernando Fonseca, E.P.E.
Amadora, 2720-276, Portugal
Hospital de Braga
Braga, 4710-243, Portugal
Centro Hospitalar e Universitário de Coimbra E.P.E
Coimbra, 3040-278, Portugal
CUF Alvalade
Lisbon, 1600-618, Portugal
Hospital Beatriz Ângelo
Loures, 2674-514, Portugal
Campus Neurologico Senior
Torres Vedras, 2560-280, Portugal
Inha University Hospital
Incheon, Gyeonggi-do, 22332, South Korea
Seoul National University Bundang Hospital
Seongnam-si, Gyeonggi-do, 13620, South Korea
Gachon University Gil Medical Center
Incheon, 21565, South Korea
Asan Medical Center
Seoul, 05505, South Korea
Samsung Medical Center
Seoul, 06351, South Korea
Konkuk University Medical Center
Seoul, 143-729, South Korea
Policlinica Guipuzcoa
Donostia / San Sebastian, Guipuzcoa, 20014, Spain
Hospital de Cruces
Barakaldo, Vizcaya, 48903, Spain
Fundacio ACE
Barcelona, 08028, Spain
Hospital Clinic i Provincial de Barcelona
Barcelona, 08036, Spain
Hospital de la Santa Creu i Sant Pau
Barcelona, 08041, Spain
Clinica Ruber
Madrid, 28006, Spain
Hospital Universitario Dr. Peset
Valencia, 46017, Spain
Hospital Universitari i Politecnic La Fe
Valencia, 46026, Spain
Changhua Christian Hospital
Changhua, 500, Taiwan
Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung City, 807, Taiwan
Kaohsiung Chang Gung Memorial Hospital
Kaohsiung City, 83301, Taiwan
National Cheng Kung University Hospital
Tainan, 704, Taiwan
National Taiwan University Hospital
Taipei, 100, Taiwan
Chang Gung Memorial Hospital, Linkou
Taoyuan, 333, Taiwan
Southmead Hospital
Bristol, Avon, BS16 1LE, United Kingdom
Re:Cognition Health Ltd
London, Greater London, W1G 9JF, United Kingdom
Charing Cross Hospital
London, Greater London, W6 8RF, United Kingdom
The National Hospital for Neurology and Neurosurgery Centre
London, Greater London, WC1N 3BG, United Kingdom
Salford Royal
Salford, Greater Manchester, M6 8HD, United Kingdom
The University of Edinburgh
Edinburgh, Lothian Region, EH8 9YL, United Kingdom
Manchester Royal Infirmary
Blackburn, Merseyside, BB3 2HH, United Kingdom
The RICE Centre
Bath, Somerset, BA1 3NG, United Kingdom
Glasgow Memory Clinic Ltd
Glasgow, Strathclyde, G20 0XA, United Kingdom
Stobhill ACH Hospital
Glasgow, Strathclyde, G21 3UW, United Kingdom
Ninewells Hospital
Dundee, Tayside Region, DD2 1GZ, United Kingdom
Newcastle University
Newcastle upon Tyne, Tyne & Wear, NE4 5PL, United Kingdom
Kingshill Research Centre
Chippenham, Wiltshire, SN15 1GG, United Kingdom
Related Publications (3)
Loomis SJ, Miller R, Castrillo-Viguera C, Umans K, Cheng W, O'Gorman J, Hughes R, Budd Haeberlein S, Whelan CD. Genome-Wide Association Studies of ARIA From the Aducanumab Phase 3 ENGAGE and EMERGE Studies. Neurology. 2024 Feb 13;102(3):e207919. doi: 10.1212/WNL.0000000000207919. Epub 2023 Dec 28.
PMID: 38165296DERIVEDMuralidharan KK, Kowalski KG, Tong X, Haeberlein SB, Rajagovindan R, Nestorov I. Characterization of exposure-Clinical Dementia Rating-Sum of Boxes relationship in subjects with early Alzheimer's disease from the aducanumab Phase 3 trials. J Pharmacokinet Pharmacodyn. 2023 Feb;50(1):45-62. doi: 10.1007/s10928-022-09839-3. Epub 2023 Jan 4.
PMID: 36600109DERIVEDSalloway S, Chalkias S, Barkhof F, Burkett P, Barakos J, Purcell D, Suhy J, Forrestal F, Tian Y, Umans K, Wang G, Singhal P, Budd Haeberlein S, Smirnakis K. Amyloid-Related Imaging Abnormalities in 2 Phase 3 Studies Evaluating Aducanumab in Patients With Early Alzheimer Disease. JAMA Neurol. 2022 Jan 1;79(1):13-21. doi: 10.1001/jamaneurol.2021.4161.
PMID: 34807243DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Limitations and Caveats
The study was halted prematurely based on a prespecified futility analysis and not based on safety concerns. Participants discontinued due to study termination are included in "Reason not Specified" category in participant flow tables above.
Results Point of Contact
- Title
- Biogen Study Medical Director
- Organization
- Biogen
Study Officials
- STUDY DIRECTOR
Medical Director
Biogen
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 18, 2015
First Posted
June 23, 2015
Study Start
August 13, 2015
Primary Completion
August 8, 2019
Study Completion
August 8, 2019
Last Updated
September 2, 2021
Results First Posted
September 2, 2021
Record last verified: 2021-08