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221AD301 Phase 3 Study of Aducanumab (BIIB037) in Early Alzheimer's Disease (ENGAGE)

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. Identifier: NCT02477800
Recruitment Status : Terminated (Study was discontinued based on futility analysis done and not based on safety concerns. Follow-up visits and closing out study activities are completed)
First Posted : June 23, 2015
Results First Posted : September 2, 2021
Last Update Posted : September 2, 2021
Information provided by (Responsible Party):

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].

Condition or disease Intervention/treatment Phase
Alzheimer's Disease Drug: Aducanumab (BIIB037) Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1653 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : August 13, 2015
Actual Primary Completion Date : August 8, 2019
Actual Study Completion Date : August 8, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Aducanumab

Arm Intervention/treatment
Experimental: Low Dose
Monthly intravenous (IV) infusion
Drug: Aducanumab (BIIB037)
Low dose

Drug: Placebo

Experimental: High Dose
Monthly intravenous (IV) infusion
Drug: Aducanumab (BIIB037)
High dose

Drug: Placebo

Primary Outcome Measures :
  1. Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SB) Score at Week 78 [ Time Frame: Baseline, 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.

Secondary Outcome Measures :
  1. Change From Baseline in Mini-Mental State Examination (MMSE) Score at Week 78 [ Time Frame: Baseline, Week 78 ]
    The MMSE is a widely used performance-based test of global cognitive status. It consists of 11 tasks that assess orientation, word recall, attention and calculation, language abilities, and visuospatial functions. The scores from the 11 tests are combined to obtain the total score, which ranges from 0 to 30, with lower scores over time indicating increasing cognitive impairment. MMRM analysis was used to analyze change from baseline in MMSE. A negative change from baseline indicates clinical decline.

  2. Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (13 Items) (ADAS-Cog 13) Score at Week 78 [ Time Frame: Baseline, Week 78 ]
    ADAS-Cog13 comprises both cognitive tasks and clinical ratings of cognitive performance. The scale items capture word recall, ability to follow commands, the ability to correctly copy or draw an image, naming, the ability to interact with everyday objects, orientation, word recognition, memory, comprehension of spoken language, word-finding, and language ability, with a measure for delayed word recall and concentration/distractibility. The total score ranges from 0 to 85. An increase in score over time indicates increasing cognitive impairment. MMRM analysis was used to analyze change from baseline in ADAS-Cog 13. A positive change from baseline indicates clinical decline.

  3. 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 [ Time Frame: Baseline, Week 78 ]
    The ADCS-ADL-MCI consists of 17 instrumental items (e.g., shopping, preparing meals, using household appliances) and 1 basic item (getting dressed). Ratings reflect caregiver observations about the patient's actual functioning over the previous month and provide an assessment of change in the functional state of the participant over time. The total score ranges from 0 to 53, with lower values over time reflecting functional deterioration. MMRM analysis was used to analyze change from baseline in ADAS-ADL-MCI. A negative change from baseline indicates clinical decline.

Information from the National Library of Medicine

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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

Key Inclusion Criteria:

  • 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

Key Exclusion Criteria:

  • 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)

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 identifier (NCT number): NCT02477800

Hide Hide 181 study locations
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United States, Arizona
St. Joseph's Hospital and Medical Center
Phoenix, Arizona, United States, 85013
Center for Neurosciences
Tucson, Arizona, United States, 85718
United States, California
Neurology Center of North Orange County
Fullerton, California, United States, 92835
Senior Clinical Trials, Inc.
Laguna Hills, California, United States, 92653
Torrance Clinical Research Institute, Inc.
Lomita, California, United States, 90717
University of California - Los Angeles
Los Angeles, California, United States, 90095
UCSF - Memory and Aging Center
San Francisco, California, United States, 94158
California Neuroscience Research Medical Group Inc.
Sherman Oaks, California, United States, 91403
Southern California Research LLC
Simi Valley, California, United States, 93065
United States, Connecticut
Institute for Neurodegenerative Disorders
New Haven, Connecticut, United States, 06510
United States, District of Columbia
Georgetown University Hospital
Washington, District of Columbia, United States, 20057
United States, Florida
Brain Matters Research, Inc.
Delray Beach, Florida, United States, 33445
Neuropsychiatric Research Center of Southwest Florida
Fort Myers, Florida, United States, 33912
Jacksonville Center for Clinical Research
Jacksonville, Florida, United States, 32216
University of Miami
Miami, Florida, United States, 33136
Miami Jewish Health Systems
Miami, Florida, United States, 33137
Compass Research Main
Orlando, Florida, United States, 32806
Palm Beach Neurological Center
Palm Beach Gardens, Florida, United States, 33410
Stedman Clinical Trials, LLC
Tampa, Florida, United States, 33613
USF Health Byrd Institute
Tampa, Florida, United States, 33616
Meridien Research
Tampa, Florida, United States, 33634
Compass Research Main
The Villages, Florida, United States, 32162
Premiere Research Institute
West Palm Beach, Florida, United States, 33407
Cleveland Clinic Florida - Weston
Weston, Florida, United States, 33331
United States, Illinois
Alexian Brothers Neurosciences Institute
Elk Grove Village, Illinois, United States, 60007
Advocate Lutheran General Hospital
Park Ridge, Illinois, United States, 60068
United States, Indiana
Fort Wayne Neurological Center
Fort Wayne, Indiana, United States, 46804
Indiana University School of Medicine
Indianapolis, Indiana, United States, 46202
United States, Kansas
University of Kansas Medical Center Research Institute, Inc.
Kansas City, Kansas, United States, 66160
Via Christi Research, a division of Via Christi Hospitals Wichita, Inc.
Wichita, Kansas, United States, 67214
United States, Kentucky
Baptist Health Lexington
Lexington, Kentucky, United States, 40503
United States, Massachusetts
Brigham & Women's Hosp End/Dbt
Boston, Massachusetts, United States, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
ActivMed Practices & Research
Methuen, Massachusetts, United States, 01844
Donald S. Marks, M.D., P.C.
Plymouth, Massachusetts, United States, 02360
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Missouri
Washington University
Saint Louis, Missouri, United States, 63131
United States, Nevada
Las Vegas Medical research
Las Vegas, Nevada, United States, 89113
United States, New Jersey
Advanced Memory Research Institute of NJ, PC
Toms River, New Jersey, United States, 08755
United States, New York
Albany Medical College
Albany, New York, United States, 12208
New York University Medical Center PRIME
New York, New York, United States, 10016
University of Rochester
Rochester, New York, United States, 14620
United States, North Carolina
ANI Neurology, PLLC d/b/a Alzheimer's Memory Center
Charlotte, North Carolina, United States, 28270
Raleigh Neurology Associates, P.A.
Raleigh, North Carolina, United States, 27607-6010
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
United States, Oklahoma
Lynn Health Science Institute
Oklahoma City, Oklahoma, United States, 73112
United States, Pennsylvania
The Clinical Trial Center, LLC
Jenkintown, Pennsylvania, United States, 19046
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
Northeastern Pennsylvania Memory and Alzheimer's Center
Plains, Pennsylvania, United States, 18705
United States, Rhode Island
Rhode Island Mood & Memory Research Institute
East Providence, Rhode Island, United States, 02915
Butler Hospital
Providence, Rhode Island, United States, 02906
United States, South Carolina
Medical University of South Carolina (MUSC)
Charleston, South Carolina, United States, 29425
United States, Tennessee
Neurology Clinic, PC
Cordova, Tennessee, United States, 38108
University of Tennessee Medical Center. Knoxville
Knoxville, Tennessee, United States, 37920
Clinical Neuroscience Solutions, Inc.
Memphis, Tennessee, United States, 38119
United States, Texas
UT Southwestern Medical Center at Dallas
Dallas, Texas, United States, 75390
Baylor College of Medicine
Houston, Texas, United States, 77030
United States, Virginia
National Clinical Research Inc.-Richmond
Richmond, Virginia, United States, 23294
United States, Wisconsin
Medical College of Wisconsin, Inc.
Milwaukee, Wisconsin, United States, 53266
Australia, New South Wales
St Vincent's Hospital Sydney
Darlinghurst, New South Wales, Australia, 2010
Central Coast Neurosciences Research, Gosford
East Gosford, New South Wales, Australia, 2250
Central Coast Neurosciences Research
Erina, New South Wales, Australia, 2250
KARA Institute for Neurological Diseases
North Ryde, New South Wales, Australia, 2113
Calvary Mater Newcastle
Waratah, New South Wales, Australia, 2298
Australia, Queensland
The Prince Charles Hospital
Chermside, Queensland, Australia, 4032
Royal Brisbane and Women's Hospital
Herston, Queensland, Australia, 4006
Toowoomba Base Hospital
Toowoomba, Queensland, Australia, 4350
Australia, Victoria
Box Hill Hospital
Box Hill, Victoria, Australia, 3128
Austin Hospital
Heidelberg, Victoria, Australia, 3084
Royal Melbourne Hospital
Parkville, Victoria, Australia, 3050
Australia, Western Australia
Neurodegenerative Disorders Research
West Perth, Western Australia, Australia, 6005
LKH - Universitaetsklinikum Graz
Graz, Austria, 8036
Christian-Doppler-Klinik - Universitätsklinikum Salzburg
Salzburg, Austria, 5020
Canada, Alberta
Heritage Medical Research Clinic
Calgary, Alberta, Canada, T2N 1N4
Canada, British Columbia
The Medical Arts Health Research Group
Penticton, British Columbia, Canada, V2A 5C8
UBC Hospital
Vancouver, British Columbia, Canada, V6T 2B5
Canada, Ontario
Toronto Memory Program (Neurology Research Inc.)
Toronto, Ontario, Canada, M3B 2S7
Toronto Sunnybrook Hospital
Toronto, Ontario, Canada, M4N 3M5
Canada, Quebec
The Montreal Neurological Institute
Montreal, Quebec, Canada, H3A 2B4
McGill Centre for Studies in Aging
Verdun, Quebec, Canada, H4H 1R3
CHU de Quebec - Hôpital de l' Enfant Jésus
Quebec, Canada, G1J 1Z4
CCBR - Ballerup - DK
Ballerup, Denmark, 2750
København Ø, Denmark, 2100
CCBR - Vejle - DK
Vejle, Denmark, 7100
CCBR - Ålborg - DK
Ålborg, Denmark, 9100
CHU Strasbourg - Hôpital Hautepierre
Strasbourg Cedex, Bas Rhin, France, 67098
Hopital Louis Pasteur Colmar
Strasbourg, Bas Rhin, France, 67091
Groupe Hospitalier Pellegrin - Hôpital Pellegrin
Bordeaux, Gironde, France, 33076
CHU Reims - Hôpital Maison Blanche
Reims, Marne, France, 51092
Hopital Neurologique Pierre Wertheimer
Bron Cedex, Rhone, France, 69677
Groupe hospitalier Broca - La Rochefoucauld - La Collégiale
Paris, France, 75013
Groupe Hospitalier Pitie-Salpetriere
Paris, France, 75013
Praxis Dr. Scholz
Boeblingen, Baden Wuerttemberg, Germany, 71034
Aerztliche Gemeinschaftspraxis
Ostfildern, Baden Wuerttemberg, Germany, 73760
Neuro MVZ Stuttgart
Stuttgart, Baden Wuerttemberg, Germany, 70182
Klinikum der Johann Wolfgang Goethe-Universitaet
Frankfurt, Bayern, Germany, 97080
Praxis Dr. med. Bergmann
Neuburg, Bayern, Germany, 86633
Neurologische Gemeinschaftspraxis Kassel
Kassel, Hessen, Germany, 34121
Klinische Forschung Hannover-Mitte GmbH
Hannover, Niedersachsen, Germany, 30159
Universitaetsklinikum Aachen AOeR
Aachen, Nordrhein Westfalen, Germany, 52074
Universitaetsklinikum Bonn AoeR
Bonn, Nordrhein Westfalen, Germany, 53127
Universitaetsklinikum Koeln
Cologne, Nordrhein Westfalen, Germany, 53105
Charite Universitaetsmedizin Berlin - Campus Benjamin Franklin
Berlin, Germany, 14050
Azienda Ospedaliero Universitaria Ospedali Riuniti
Torrette Di Ancona, Ancona, Italy, 60126
Fondazione Istituto G.Giglio di Cefalù
Cefalù, Palermo, Italy, 90015
Azienda Ospedaliera Ospedali Riuniti di Bergamo
Bergamo, Italy, 24100
Azienda Ospedaliera Spedali Civili di Brescia
Brescia, Italy, 25100
Azienda Ospedaliero Universitaria San Martino
Genova, Italy, 16132
Ospedale San Raffaele
Milano, Italy, 20132
Casa di Cura del Policlinico
Milano, Italy, 20144
Azienda Ospedaliera Universitaria "Federico II"
Napoli, Italy, 80131
Seconda Università degli Studi di Napoli
Napoli, Italy, 80138
Azienda Ospedaliero Universitaria Pisana
Pisa, Italy, 56126
Policlinico Universitario Agostino Gemelli
Roma, Italy, 00168
Azienda Ospedaliera Universitaria OO. RR. S. Giovanni di Dio e Ruggi D'Aragona
Salerno, Italy, 84131
A.O.U. Senese Policlinico Santa Maria alle Scotte
Siena, Italy, 53100
Research Site
Chiba-Shi, Chiba-Ken, Japan, 263-0043
Research Site
Inzai-shi, Chiba-Ken, Japan
Research Site
Kurume-shi, Fukuoka-ken, Japan, 830-0011
Research Site
Aizuwakamatsu-shi, Fukushima-Ken, Japan, 965-8585
Research Site
Asahikawa-shi, Hokkaido, Japan, 070-8644
Research Site
Sapporo-shi, Hokkaido, Japan, 006-8555
Research Site
Sapporo-shi, Hokkaido, Japan, 064-8570
Research Site
Atsugi-shi, Kanagawa-Ken, Japan, 243-8551
Research Site
Kamakura-shi, Kanagawa-Ken, Japan, 247-8533
Research Site
Kawasaki-Shi, Kanagawa-Ken, Japan, 211-8533
Yokohama-shi, Kanagawa-ken, Japan, 223-0059
Research Site
Yokohama-shi, Kanagawa-Ken, Japan, 225-0013
Research Site
Yokohama-shi, Kanagawa-Ken, Japan, 225-0025
Research Site
Kyoto-shi, Kyoto-Fu, Japan, 616-8255
Research Site
Nagaoka-shi, Niigata-Ken, Japan, 940-2081
Research Site
Iruma-gun, Saitama-Ken, Japan, 350-0495
Research Site
Kasukabe-shi, Saitama-Ken, Japan, 344-0036
Research Site
Bunkyo-ku, Tokyo-To, Japan, 113-0034
Research Site
Shinjuku-ku (I), Tokyo-To, Japan, 162-8655
Research Site
Shinjuku-ku, Tokyo-To, Japan, 162-8655
Research Site
Ota-ku, Tokyo, Japan, 143-8541
Research Site
Yamagata-shi, Yamagata-Ken, Japan, 990-0834
Research Site
Itabashi-ku, Japan, 173-0015
Research Site
Itabashi-ku, Japan, 173-8610
Research Site
Kiyose-shi, Japan
Research Site
Kodaira-shi, Japan, 187-8551
Korea, Republic of
Inha University Hospital
Incheon, Gyeonggi-do, Korea, Republic of, 22332
Seoul National University Bundang Hospital
Seongnam-si, Gyeonggi-do, Korea, Republic of, 13620
Gachon University Gil Medical Center
Incheon, Korea, Republic of, 21565
Asan Medical Center
Seoul, Korea, Republic of, 05505
Samsung Medical Center
Seoul, Korea, Republic of, 06351
Konkuk University Medical Center
Seoul, Korea, Republic of, 143-729
Hospital Professor Doutor Fernando Fonseca, E.P.E.
Amadora, Portugal, 2720-276
Hospital de Braga
Braga, Portugal, 4710-243
Centro Hospitalar e Universitário de Coimbra E.P.E
Coimbra, Portugal, 3040-278
CUF Alvalade
Lisboa, Portugal, 1600-618
Hospital Beatriz Ângelo
Loures, Portugal, 2674-514
Campus Neurologico Senior
Torres Vedras, Portugal, 2560-280
Policlinica Guipuzcoa
San Sebastian, Guipuzcoa, Spain, 20014
Hospital de Cruces
Barakaldo, Vizcaya, Spain, 48903
Fundacio ACE
Barcelona, Spain, 08028
Hospital Clinic i Provincial de Barcelona
Barcelona, Spain, 08036
Hospital de la Santa Creu i Sant Pau
Barcelona, Spain, 08041
Clinica Ruber
Madrid, Spain, 28006
Hospital Universitario Dr. Peset
Valencia, Spain, 46017
Hospital Universitari i Politecnic La Fe
Valencia, Spain, 46026
Changhua Christian Hospital
Changhua, Taiwan, 500
Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung, Taiwan, 807
Kaohsiung Chang Gung Memorial Hospital
Kaohsiung, Taiwan, 83301
National Cheng Kung University Hospital
Tainan, Taiwan, 704
National Taiwan University Hospital
Taipei, Taiwan, 100
Chang Gung Memorial Hospital, Linkou
Taoyuan County, Taiwan, 333
United Kingdom
Southmead Hospital
Bristol, Avon, United Kingdom, BS16 1LE
Re:Cognition Health Ltd
London, Greater London, United Kingdom, W1G 9JF
Charing Cross Hospital
London, Greater London, United Kingdom, W6 8RF
The National Hospital for Neurology and Neurosurgery Centre
London, Greater London, United Kingdom, WC1N 3BG
Salford Royal
Salford, Greater Manchester, United Kingdom, M6 8HD
The University of Edinburgh
Edinburgh, Lothian Region, United Kingdom, EH8 9YL
Manchester Royal Infirmary
Blackburn, Merseyside, United Kingdom, BB3 2HH
The RICE Centre
Bath, Somerset, United Kingdom, BA1 3NG
Glasgow Memory Clinic Ltd
Glasgow, Strathclyde, United Kingdom, G20 0XA
Stobhill ACH Hospital
Glasgow, Strathclyde, United Kingdom, G21 3UW
Ninewells Hospital
Dundee, Tayside Region, United Kingdom, DD2 1GZ
Newcastle University
Newcastle upon Tyne, Tyne & Wear, United Kingdom, NE4 5PL
Kingshill Research Centre
Chippenham, Wiltshire, United Kingdom, SN15 1GG
Sponsors and Collaborators
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Study Director: Medical Director Biogen
  Study Documents (Full-Text)

Documents provided by Biogen:
Study Protocol  [PDF] June 28, 2018
Statistical Analysis Plan  [PDF] September 11, 2018

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Biogen Identifier: NCT02477800    
Other Study ID Numbers: 221AD301
2015-000966-72 ( EudraCT Number )
First Posted: June 23, 2015    Key Record Dates
Results First Posted: September 2, 2021
Last Update Posted: September 2, 2021
Last Verified: August 2021
Keywords provided by Biogen:
Additional relevant MeSH terms:
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Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders