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
221AD302 Phase 3 Study of Aducanumab (BIIB037) in Early Alzheimer's Disease
EMERGE
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
1,643
13 countries
180
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 Sep 2015
Typical duration for phase_3
180 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 29, 2015
CompletedStudy Start
First participant enrolled
September 15, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 5, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
August 5, 2019
CompletedResults Posted
Study results publicly available
September 2, 2021
CompletedSeptember 2, 2021
August 1, 2021
3.9 years
June 18, 2015
July 1, 2021
August 9, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Change From Baseline in Clinical Dementia Rating Scale - 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) 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) infusions
High Dose
EXPERIMENTALMonthly intravenous (IV) infusions
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 (180)
University of Alabama at Birmingham
Birmingham, Alabama, 35233, United States
Banner Alzheimer's Institute
Phoenix, Arizona, 85006, United States
Xenoscience Inc.
Phoenix, Arizona, 85013, United States
Banner Sun Health Research Institute
Sun City, Arizona, 85351, United States
Institute for Memory Impairments
Irvine, California, 92607, United States
Renewal Behavioral Health
Long Beach, California, 85013, United States
USC Keck School of Medicine
Los Angeles, California, 90033, United States
Hoag Memorial Hospital Presbyterian
Newport Beach, California, 92663, United States
Excell Research, Inc.
Oceanside, California, 92056, United States
Pacific Neuroscience Medical Group
Oxnard, California, 93030, United States
Anderson Clinical Research
Redlands, California, 92354, United States
Pacific Research Network
San Diego, California, 92103, United States
University of California San Diego Medical Center
San Diego, California, 92103, United States
California Pacific Medical Center
San Francisco, California, 94114, United States
Syrentis Clinical Research
Santa Ana, California, 92705, United States
St Joseph Heritage Healthcare
Santa Rosa, California, 95403, United States
Stanford University Medical Center
Stanford, California, 94305, United States
University Of Colorado Denver
Aurora, Colorado, 80045, United States
IMMUNOe International Research Centers
Thornton, Colorado, 80233, United States
Associated Neurologists of Southern Connecticut, PC
Fairfield, Connecticut, 06824, United States
Yale University School Of Medicine
New Haven, Connecticut, 06520, United States
Research Center for Clinical Studies, Inc.
Norwalk, Connecticut, 06851, United States
JEM Research Institute
Atlantis, Florida, 33462, United States
Bradenton Research Center, Inc.
Bradenton, Florida, 34205, United States
Meridien Research
Brooksville, Florida, 34601, United States
Quantum Laboratories Inc.
Deerfield Beach, Florida, 33064, United States
Infinity Clinical Research, LLC
Hollywood, Florida, 33021, United States
Mayo Clinic in Florida
Jacksonville, Florida, 32224, United States
Renstar Medical Research
Ocala, Florida, 34470, United States
Clinical Neuroscience Solutions, Inc.
Orlando, Florida, 32801, United States
Axiom Clinical Research of Florida
Tampa, Florida, 33609, United States
Emory University Cognitive Neurology Clinic & ADRC
Atlanta, Georgia, 30329, United States
Medical Research Health and Education Foundation, Inc
Columbus, Georgia, 31909, United States
NeuroStudies.net, LLC
Decatur, Georgia, 30033, United States
Josephson, Wallack, Munshower Neurology, PC
Indianapolis, Indiana, 46256, United States
McLean Hospital
Belmont, Massachusetts, 02478, United States
Boston Center for Memory
Newton, Massachusetts, 05201, United States
Hattiesburg Clinic, PA
Hattiesburg, Mississippi, 39401, United States
Cleveland Clinic Lou Ruvo Center for Brain Health
Las Vegas, Nevada, 89106, United States
ActivMed Practices & Research
Portsmouth, New Hampshire, 03801, United States
AdvanceMed Research
Lawrenceville, New Jersey, 08648, United States
Empire Neurology, PC
Latham, New York, 12110, United States
Weill Cornell Medical College-New York Presbyterian Hospital
New York, New York, 10021, United States
Mount Sinai School of Medicine
New York, New York, 10029, United States
PMG Research of Winston-Salem, LLC
Winston-Salem, North Carolina, 27103, United States
Wake Forest Baptist Health
Winston-Salem, North Carolina, 27103, United States
Ohio State University Medical Center
Dublin, Ohio, 43017, United States
Lehigh Center for Clinical Research, LLC
Allentown, Pennsylvania, 18104, United States
Penn Memory Center
Philadelphia, Pennsylvania, 19104, United States
Rhode Island Hospital
Providence, Rhode Island, 02903, United States
Roper St. Francis Healthcare
North Charleston, South Carolina, 29406-6076, United States
Senior Adult Specialty Research
Austin, Texas, 78757, United States
The Methodist Hospital Research Institute
Houston, Texas, 77030, United States
Clinical Trial Network
Houston, Texas, 77074, United States
University of Utah Health Sciences Center
Salt Lake City, Utah, 84132, United States
Clinical Neuroscience Research Association, Inc
Bennington, Vermont, 05201, United States
University of Washington Medical Center
Seattle, Washington, 98195, United States
Northwest Neurological, PLLC
Spokane, Washington, 99202, United States
A.Z. Klina
Brasschaat, Belgium
AZ Sint-Jan Brugge
Bruges, 8000, Belgium
Universitair Ziekenhuis Brussel
Brussels, 1090, Belgium
Centre Neurologique & de Réadaptation Fonctionnelle
Fraiture, 4557, Belgium
Universitair Ziekenhuis Gent
Ghent, 9000, Belgium
AZ Groeninge - Campus Kennedylaan
Kortrijk, 8500, Belgium
UZ Leuven
Leuven, 3000, Belgium
AZ Delta
Roeselare, 8800, Belgium
Health Research.
Kamloops, British Columbia, Canada
Health Research
West Vancouver, British Columbia, Canada
True North Clinical Research - Halifax Inc.
Halifax, Nova Scotia, B3S 1M7, Canada
True North Clinical Research Kentville, Inc
Kentville, Nova Scotia, B4N 4K9, Canada
JBN Medical Diagnostic Services Inc.
Burlington, Ontario, L7M 4Y1, Canada
St. Joseph's HC- Parkwood Institute
London, Ontario, N6C 5J1, Canada
Bruyere Continuing Care
Ottawa, Ontario, K1N 5C8, Canada
Kawartha Regional Memory Clinic
Peterborough, Ontario, K9H 2P4, Canada
Toronto Western Hospital
Toronto, Ontario, M5T 2S8, Canada
Recherches Neuro-Hippocampe Inc.
Gatineau, Quebec, J8T 8J1, Canada
Recherche Sepmus, Inc.
Greenfield Park, Quebec, J4V 2J2, Canada
DIEX Recherche Sherbrooke Inc.
Sherbrooke, Quebec, J1H 1Z1, Canada
Douglas Hospital Research Centre
Verdun, Quebec, H4H 1R3, Canada
Terveystalo Kamppi
Helsinki, 00100, Finland
Itä-Suomen yliopisto, Aivotutkimusyksikkö
Kuopio, 70210, Finland
CRST, Clinical Research Services Turku
Turku, 20520, Finland
Hôpital de la Timone
Marseille, Bouches-du-Rhône, 13385, France
Centre de Recherche Clinique du Gérontopôle - Cité de la Santé
Toulouse, Haute Garonne, 31052, France
CHU de Toulouse - Hôpital Purpan
Toulouse, Haute Garonne, 31059, France
Hôpital Gui de Chauliac
Montpellier, Herault, 34295, France
CHU Rennes - Hopital Pontchaillou
Rennes, Ille Et Vilaine, 35033, France
CHU Nantes - Hopital Nord Laënnec
Nantes, Loire Atlantique, 44093, France
Hopital Roger Salengro - CHU Lille
Lille, Nord, 59037, France
Hôpital des Charpennes
Villeurbanne, Rhone, 69100, France
Hôpital Fernand Widal
Paris, 75010, France
Bezirkskrankenhaus Guenzburg
Gunzburg, Baden-Wurttemberg, 89312, Germany
ISPG - Institut fuer Studien zur Psychischen Gesundheit
Mannheim, Baden-Wurttemberg, 68165, Germany
Nervenfachaerztlichen Gemeinschaftspraxis Ulm
Ulm, Baden-Wurttemberg, 89078, Germany
Universitaetsklinikum Ulm
Ulm, Baden-Wurttemberg, 89081, Germany
Klinik Hohe Warte Bayreuth
Bayreuth, Bavaria, 95445, Germany
Institut fuer Schlaganfall- und Demenzforschung (ISD)
Munich, Bavaria, 81377, Germany
Klinikum rechts der Isar der TU Muenchen
Munich, Bavaria, 81675, Germany
Neuropraxis Muenchen Sued
Unterhaching, Bavaria, 82008, Germany
Neuro Centrum Odenwald
Erbach im Odenwald, Hesse, 64711, Germany
Schwerpunktpraxis fuer Neurologie, Psychiatrie und Klinische Studien
Bielefeld, North Rhine-Westphalia, 33647, Germany
Universitaetsklinikum Duesseldorf AoeR
Düsseldorf, North Rhine-Westphalia, 40629, Germany
Universitaetsklinikum Muenster
Münster, North Rhine-Westphalia, 48149, Germany
Zentrum f. Neurologisch- Psychiatrische Studien und Begutachtung
Siegen, North Rhine-Westphalia, 57076, Germany
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
Mainz, Rhineland-Palatinate, 55131, Germany
Klinikum Chemnitz gGmbH
Chemnitz, Saxony, 09131, Germany
Kopfzentrum Leipzig
Leipzig, Saxony, 04275, Germany
Klinikum Altenburger Land GmbH
Altenburg, Thuringia, 04600, Germany
emovis GmbH
Berlin, 10629, Germany
Neurologie im Tempelhofer Hafen
Berlin, 12099, Germany
Ospedale degli Infermi
Ponderano, Biella, 13875, Italy
Azienda Ospedaliera Card. G. Panico
Tricase, Lecce, 73039, Italy
ASST di Monza
Monza, Milano, 20052, Italy
Fondazione IRCCS Istituto Neurologico Carlo Besta
Milan, 20133, Italy
Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone
Palermo, 90100, Italy
Azienda Ospedaliera di Perugia Ospedale S. Maria della Misericordia
Perugia, 06156, Italy
Fondazione Santa Lucia IRCCS
Roma, 00179, Italy
Umberto I Pol. di Roma-Università di Roma La Sapienza
Roma, 00185, Italy
Research Site
Obu-shi, Aichi-ken, 474-8511, Japan
Research Site
Toon-shi, Ehime, 791-0295, Japan
Research Site
Fukuoka, Fukuoka, 814-0180, Japan
Research Site
Kurume-shi, Fukuoka, 830-0011, Japan
Research Site
Otake-shi, Hiroshima, 739-0696, Japan
Research Site
Amagasaki-shi, Hyōgo, 660-8511, Japan
Research site
Himeji-shi, Hyōgo, 670-0981, Japan
Research Site
Himeji-shi, Hyōgo, 672-8043, Japan
Research Site
Kobe, Hyōgo, 650-0047, Japan
Research Site
Kita-gun, Kagawa-ken, 761-0793, Japan
Research Site
Kyoto, Kyoto, 607-8113, Japan
Research Site
Kyoto, Kyoto, 616-8255, Japan
Research Site
Tsu, Mie-ken, 514-8507, Japan
Research Site
Nishisonogi, Nagasaki, 851-2103, Japan
Research Site
Yufu-shi, Oita Prefecture, 879-5593, Japan
Research Site
Kurashiki-shi, Okayama-ken, 710-0813, Japan
Research Site
Okayama, Okayama-ken, 703-8265, Japan
Research Site
Tsukuba-gun, Okayama-ken, 701-0304, Japan
Research Site
Kishiwada-shi, Osaka, 596-8522, Japan
Research Site
Osaka, Osaka, 530-0001, Japan
Research Site
Osaka, Osaka, 545-8586, Japan
Research Site
Osaka, Osaka, 553-0003, Japan
Research Site
Sennan-shi, Osaka, 590-0503, Japan
Research Site
Suita-shi, Osaka, 565-0871, Japan
Research Site
Iwata-shi, Shizuoka, 438-0043, Japan
Research Site
Shizuoka, Shizuoka, 420-8688, Japan
Research Site
Shizuoka, Shizuoka, 424-8636, Japan
Alzheimer Research Center
Amsterdam, 1081 GM, Netherlands
Erasmus Medisch Centrum
Rotterdam, 3015 CE, Netherlands
Podlaskie Centrum Psychogeriatrii
Bialystok, 15-732, Poland
PALLMED Sp. z o.o.
Bydgoszcz, 85-796, Poland
Uniwersyteckie Centrum Kliniczne
Gdansk, Poland
Novo-Med Zielinski i wspolnicy Sp. j.
Katowice, 40-650, Poland
SPZOZ Centralny Szpital Kliniczny UM w Lodzi
Lodz, 92-216, Poland
Centrum Diagnostyczno - Terapeutyczne "MEDICUS" Sp.z o.o.
Lubin, 59-300, Poland
Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie
Lublin, 20-950, Poland
Neurologiczny NZOZ Centrum Leczenia SM
Plewiska, 62-064, Poland
NZOZ "NEURO-KARD", "Ilkowski i Partnerzy" Sp. Partn. Lek.
Poznan, 61-853, Poland
Centrum Medyczne Medyk
Rzeszów, 35-055, Poland
NZOZ "SENIOR" Poradnia Psychogeriatryczna
Sopot, 81-855, Poland
Osrodek Badan Klinicznych EUROMEDIS
Szczecin, 70-111, Poland
Neuro-Care Gabriela Klodowska
Śląskie, 41-100, Poland
mMED Maciej Czarnecki
Warsaw, 01-697, Poland
Hospital General Universitario de Elche
Elche, Alicante, 3203, Spain
ALTHAIA Hospital Sant Joan de Deu
Manresa, Barcelona, 08243, Spain
Hospital Universitario Reina Sofía
Córdoba, Córdoba, 14011, Spain
Clinica Universidad de Navarra
Pamplona, Navarre, 31008, Spain
Hospital del Mar
Barcelona, 08003, Spain
Hospital Universitari Quiron Dexeus
Barcelona, 08028, Spain
Hospital Universitari de Bellvitge
Barcelona, 8907, Spain
Hospital Universitari Arnau de Vilanova
Lleida, 25198, Spain
Hospital Universitario Virgen Macarena
Seville, 41009, Spain
Skånes Universitetssjukhus, Malmö
Malmo, 20502, Sweden
Sahlgrenska Universitetssjukhuset, Mölndal Sjukhus
Mölndal, 43141, Sweden
Karolinska Universitetssjukhuset, Huddinge
Stockholm, 14186, Sweden
Akademiska Sjukhuset
Uppsala, 75185, Sweden
Universitären Psychiatrischen Kliniken Basel (UPK)
Basel, 4025, Switzerland
Medizinisches Zentrum MZB Biel
Biel/Bienne, 2502, Switzerland
Hôpitaux Universitaires de Genève - HUG
Geneva, 1211, Switzerland
Centre Hospitalier Universitaire Vaudois
Lausanne, CH-1011, Switzerland
Ospedale Civico
Lugano, 6903, Switzerland
Institut fuer Regenerative Medizin (IREM) der Universitaet Zuerich, Zentrum fuer Praevention und Demenztherapie
Schlieren, 8952, Switzerland
Related Publications (4)
Burton J, Brothers HM, Hutchison RM, Murphy J, Sun T, Dent G, Curiale G, Kowalski K. Lower baseline amyloid beta burden is associated with greater percent of amyloid beta positron emission tomography reduction and better clinical outcomes in the aducanumab Phase 3 trials ENGAGE and EMERGE in early Alzheimer's disease. J Prev Alzheimers Dis. 2025 Aug;12(7):100202. doi: 10.1016/j.tjpad.2025.100202. Epub 2025 May 24.
PMID: 40413110DERIVEDLoomis 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 29, 2015
Study Start
September 15, 2015
Primary Completion
August 5, 2019
Study Completion
August 5, 2019
Last Updated
September 2, 2021
Results First Posted
September 2, 2021
Record last verified: 2021-08