221AD302 Phase 3 Study of Aducanumab (BIIB037) in Early Alzheimer's Disease (EMERGE)

• ClinicalTrials.gov Identifier: NCT02484547
• Recruitment Status: Terminated
• First Posted: June 29, 2015
• Results First Posted: September 2, 2021
• Last Update Posted: September 2, 2021
• Sponsor: Biogen
• Information provided by (Responsible Party): Biogen

Study Description

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1643 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: September 15, 2015
• Actual Primary Completion Date: August 5, 2019
• Actual Study Completion Date: August 5, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Low Dose; Monthly intravenous (IV) infusions	Drug: Aducanumab (BIIB037); Low dose; Drug: Placebo; Placebo
Experimental: High Dose; Monthly intravenous (IV) infusions	Drug: Aducanumab (BIIB037); High dose; Drug: Placebo; Placebo

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in Clinical Dementia Rating Scale - 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) 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.

Eligibility Criteria

• Ages Eligible for Study: 50 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Alabama

University of Alabama at Birmingham

Birmingham, Alabama, United States, 35233

United States, Arizona

Banner Alzheimer's Institute

Phoenix, Arizona, United States, 85006

Xenoscience Inc.

Phoenix, Arizona, United States, 85013

Banner Sun Health Research Institute

Sun City, Arizona, United States, 85351

United States, California

Institute for Memory Impairments

Irvine, California, United States, 92607

Renewal Behavioral Health

Long Beach, California, United States, 85013

USC Keck School of Medicine

Los Angeles, California, United States, 90033

Hoag Memorial Hospital Presbyterian

Newport Beach, California, United States, 92663

Excell Research, Inc.

Oceanside, California, United States, 92056

Pacific Neuroscience Medical Group

Oxnard, California, United States, 93030

Anderson Clinical Research

Redlands, California, United States, 92354

Pacific Research Network

San Diego, California, United States, 92103

University of California San Diego Medical Center

San Diego, California, United States, 92103

California Pacific Medical Center

San Francisco, California, United States, 94114

Syrentis Clinical Research

Santa Ana, California, United States, 92705

St Joseph Heritage Healthcare

Santa Rosa, California, United States, 95403

Stanford University Medical Center

Stanford, California, United States, 94305

United States, Colorado

University Of Colorado Denver

Aurora, Colorado, United States, 80045

IMMUNOe International Research Centers

Thornton, Colorado, United States, 80233

United States, Connecticut

Associated Neurologists of Southern Connecticut, PC

Fairfield, Connecticut, United States, 06824

Yale University School Of Medicine

New Haven, Connecticut, United States, 06520

Research Center for Clinical Studies, Inc.

Norwalk, Connecticut, United States, 06851

United States, Florida

JEM Research Institute

Atlantis, Florida, United States, 33462

Bradenton Research Center, Inc.

Bradenton, Florida, United States, 34205

Meridien Research

Brooksville, Florida, United States, 34601

Quantum Laboratories Inc.

Deerfield Beach, Florida, United States, 33064

Infinity Clinical Research, LLC

Hollywood, Florida, United States, 33021

Mayo Clinic in Florida

Jacksonville, Florida, United States, 32224

Renstar Medical Research

Ocala, Florida, United States, 34470

Clinical Neuroscience Solutions, Inc.

Orlando, Florida, United States, 32801

Axiom Clinical Research of Florida

Tampa, Florida, United States, 33609

United States, Georgia

Emory University Cognitive Neurology Clinic & ADRC

Atlanta, Georgia, United States, 30329

Medical Research Health and Education Foundation, Inc

Columbus, Georgia, United States, 31909

NeuroStudies.net, LLC

Decatur, Georgia, United States, 30033

United States, Indiana

Josephson, Wallack, Munshower Neurology, PC

Indianapolis, Indiana, United States, 46256

United States, Massachusetts

McLean Hospital

Belmont, Massachusetts, United States, 02478

Boston Center for Memory

Newton, Massachusetts, United States, 05201

United States, Mississippi

Hattiesburg Clinic, PA

Hattiesburg, Mississippi, United States, 39401

United States, Nevada

Cleveland Clinic Lou Ruvo Center for Brain Health

Las Vegas, Nevada, United States, 89106

United States, New Hampshire

ActivMed Practices & Research

Portsmouth, New Hampshire, United States, 03801

United States, New Jersey

AdvanceMed Research

Lawrenceville, New Jersey, United States, 08648

United States, New York

Empire Neurology, PC

Latham, New York, United States, 12110

Weill Cornell Medical College-New York Presbyterian Hospital

New York, New York, United States, 10021

Mount Sinai School of Medicine

New York, New York, United States, 10029

United States, North Carolina

PMG Research of Winston-Salem, LLC

Winston-Salem, North Carolina, United States, 27103

Wake Forest Baptist Health

Winston-Salem, North Carolina, United States, 27103

United States, Ohio

Ohio State University Medical Center

Dublin, Ohio, United States, 43017

United States, Pennsylvania

Lehigh Center for Clinical Research, LLC

Allentown, Pennsylvania, United States, 18104

Penn Memory Center

Philadelphia, Pennsylvania, United States, 19104

United States, Rhode Island

Rhode Island Hospital

Providence, Rhode Island, United States, 02903

United States, South Carolina

Roper St. Francis Healthcare

North Charleston, South Carolina, United States, 29406-6076

United States, Texas

Senior Adult Specialty Research

Austin, Texas, United States, 78757

The Methodist Hospital Research Institute

Houston, Texas, United States, 77030

Clinical Trial Network

Houston, Texas, United States, 77074

United States, Utah

University of Utah Health Sciences Center

Salt Lake City, Utah, United States, 84132

United States, Vermont

Clinical Neuroscience Research Association, Inc

Bennington, Vermont, United States, 05201

United States, Washington

University of Washington Medical Center

Seattle, Washington, United States, 98195

Northwest Neurological, PLLC

Spokane, Washington, United States, 99202

Belgium

A.Z. Klina

Brasschaat, Belgium

AZ Sint-Jan Brugge

Brugge, Belgium, 8000

Universitair Ziekenhuis Brussel

Bruxelles, Belgium, 1090

Centre Neurologique & de Réadaptation Fonctionnelle

Fraiture, Belgium, 4557

Universitair Ziekenhuis Gent

Gent, Belgium, 9000

AZ Groeninge - Campus Kennedylaan

Kortrijk, Belgium, 8500

UZ Leuven

Leuven, Belgium, 3000

AZ Delta

Roeselare, Belgium, 8800

Canada, British Columbia

Health Research.

Kamloops, British Columbia, Canada

Health Research

West Vancouver, British Columbia, Canada

Canada, Nova Scotia

True North Clinical Research - Halifax Inc.

Halifax, Nova Scotia, Canada, B3S 1M7

True North Clinical Research Kentville, Inc

Kentville, Nova Scotia, Canada, B4N 4K9

Canada, Ontario

JBN Medical Diagnostic Services Inc.

Burlington, Ontario, Canada, L7M 4Y1

St. Joseph's HC- Parkwood Institute

London, Ontario, Canada, N6C 5J1

Bruyere Continuing Care

Ottawa, Ontario, Canada, K1N 5C8

Kawartha Regional Memory Clinic

Peterborough, Ontario, Canada, K9H 2P4

Toronto Western Hospital

Toronto, Ontario, Canada, M5T 2S8

Canada, Quebec

Recherches Neuro-Hippocampe Inc.

Gatineau, Quebec, Canada, J8T 8J1

Recherche Sepmus, Inc.

Greenfield Park, Quebec, Canada, J4V 2J2

DIEX Recherche Sherbrooke Inc.

Sherbrooke, Quebec, Canada, J1H 1Z1

Douglas Hospital Research Centre

Verdun, Quebec, Canada, H4H 1R3

Finland

Terveystalo Kamppi

Helsinki, Finland, 00100

Itä-Suomen yliopisto, Aivotutkimusyksikkö

Kuopio, Finland, 70210

CRST, Clinical Research Services Turku

Turku, Finland, 20520

France

Hôpital de la Timone

Marseille, Bouches-du-Rhône, France, 13385

CHU de Toulouse - Hôpital Purpan

Toulouse cedex 9, Haute Garonne, France, 31059

Centre de Recherche Clinique du Gérontopôle - Cité de la Santé

Toulouse, Haute Garonne, France, 31052

Hôpital Gui de Chauliac

Montpellier, Herault, France, 34295

CHU Rennes - Hopital Pontchaillou

Rennes cedex 09, Ille Et Vilaine, France, 35033

CHU Nantes - Hopital Nord Laënnec

Nantes cedex 1, Loire Atlantique, France, 44093

Hopital Roger Salengro - CHU Lille

Lille Cedex, Nord, France, 59037

Hôpital des Charpennes

Villeurbanne, Rhone, France, 69100

Hôpital Fernand Widal

Paris, France, 75010

Germany

Bezirkskrankenhaus Guenzburg

Gunzburg, Baden Wuerttemberg, Germany, 89312

ISPG - Institut fuer Studien zur Psychischen Gesundheit

Mannheim, Baden Wuerttemberg, Germany, 68165

Nervenfachaerztlichen Gemeinschaftspraxis Ulm

Ulm, Baden Wuerttemberg, Germany, 89078

Universitaetsklinikum Ulm

Ulm, Baden Wuerttemberg, Germany, 89081

Klinik Hohe Warte Bayreuth

Bayreuth, Bayern, Germany, 95445

Institut fuer Schlaganfall- und Demenzforschung (ISD)

Muenchen, Bayern, Germany, 81377

Klinikum rechts der Isar der TU Muenchen

Muenchen, Bayern, Germany, 81675

Neuropraxis Muenchen Sued

Unterhaching, Bayern, Germany, 82008

Neuro Centrum Odenwald

Erbach, Hessen, Germany, 64711

Universitaetsklinikum Duesseldorf AoeR

Duesseldorf, Nordrhein Westfalen, Germany, 40629

Universitaetsklinikum Muenster

Muenster, Nordrhein Westfalen, Germany, 48149

Zentrum f. Neurologisch- Psychiatrische Studien und Begutachtung

Siegen, Nordrhein Westfalen, Germany, 57076

Schwerpunktpraxis fuer Neurologie, Psychiatrie und Klinische Studien

Bielefeld, North Rhine-Westphalia, Germany, 33647

Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz

Mainz, Rheinland Pfalz, Germany, 55131

Klinikum Chemnitz gGmbH

Chemnitz, Sachsen, Germany, 09131

Kopfzentrum Leipzig

Leipzig, Sachsen, Germany, 04275

Klinikum Altenburger Land GmbH

Altenburg, Thueringen, Germany, 04600

emovis GmbH

Berlin, Germany, 10629

Neurologie im Tempelhofer Hafen

Berlin, Germany, 12099

Italy

Ospedale degli Infermi

Ponderano, Biella, Italy, 13875

Azienda Ospedaliera Card. G. Panico

Tricase, Lecce, Italy, 73039

ASST di Monza

Monza, Milano, Italy, 20052

Fondazione IRCCS Istituto Neurologico Carlo Besta

Milano, Italy, 20133

Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone

Palermo, Italy, 90100

Azienda Ospedaliera di Perugia Ospedale S. Maria della Misericordia

Perugia, Italy, 06156

Fondazione Santa Lucia IRCCS

Roma, Italy, 00179

Umberto I Pol. di Roma-Università di Roma La Sapienza

Roma, Italy, 00185

Japan

Research Site

Obu-shi, Aichi-Ken, Japan, 474-8511

Research Site

Toon-shi, Ehime-Ken, Japan, 791-0295

Research Site

Fukuoka-shi, Fukuoka-Ken, Japan, 814-0180

Research Site

Kurume-shi, Fukuoka-Ken, Japan, 830-0011

Research Site

Otake-shi, Hiroshima-Ken, Japan, 739-0696

Research Site

Amagasaki-shi, Hyogo-Ken, Japan, 660-8511

Research site

Himeji-shi, Hyogo-Ken, Japan, 670-0981

Research Site

Himeji-shi, Hyogo-Ken, Japan, 672-8043

Research Site

Kobe-shi, Hyogo-Ken, Japan, 650-0047

Research Site

Kita-gun, Kagawa-Ken, Japan, 761-0793

Research Site

Kyoto-shi, Kyoto-Fu, Japan, 607-8113

Research Site

Kyoto-shi, Kyoto-Fu, Japan, 616-8255

Research Site

Tsu-shi, Mie-Ken, Japan, 514-8507

Research Site

Nishisonogi, Nagasaki-Ken, Japan, 851-2103

Research Site

Yufu-shi, Oita-Ken, Japan, 879-5593

Research Site

Kurashiki-shi, Okayama-Ken, Japan, 710-0813

Research Site

Okayama-shi, Okayama-Ken, Japan, 703-8265

Research Site

Tsukuba-gun, Okayama-Ken, Japan, 701-0304

Research Site

Kishiwada-shi, Osaka-Fu, Japan, 596-8522

Research Site

Osaka-shi, Osaka-Fu, Japan, 530-0001

Research Site

Osaka-shi, Osaka-Fu, Japan, 545-8586

Research Site

Osaka-shi, Osaka-Fu, Japan, 553-0003

Research Site

Sennan-shi, Osaka-Fu, Japan, 590-0503

Research Site

Suita-shi, Osaka-Fu, Japan, 565-0871

Research Site

Iwata-shi, Shizuoka-Ken, Japan, 438-0043

Research Site

Shizuoka-shi, Shizuoka-Ken, Japan, 420-8688

Research Site

Shizuoka-shi, Shizuoka-Ken, Japan, 424-8636

Netherlands

Alzheimer Research Center

Amsterdam, Netherlands, 1081 GM

Erasmus Medisch Centrum

Rotterdam, Netherlands, 3015 CE

Poland

Podlaskie Centrum Psychogeriatrii

Bialystok, Poland, 15-732

PALLMED Sp. z o.o.

Bydgoszcz, Poland, 85-796

Uniwersyteckie Centrum Kliniczne

Gdansk, Poland

Novo-Med Zielinski i wspolnicy Sp. j.

Katowice, Poland, 40-650

SPZOZ Centralny Szpital Kliniczny UM w Lodzi

Lodz, Poland, 92-216

Centrum Diagnostyczno - Terapeutyczne "MEDICUS" Sp.z o.o.

Lubin, Poland, 59-300

Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie

Lublin, Poland, 20-950

Neurologiczny NZOZ Centrum Leczenia SM

Plewiska, Poland, 62-064

NZOZ "NEURO-KARD", "Ilkowski i Partnerzy" Sp. Partn. Lek.

Poznan, Poland, 61-853

Centrum Medyczne Medyk

Rzeszow, Poland, 35-055

Neuro-Care Gabriela Klodowska

Slaskie, Poland, 41-100

NZOZ "SENIOR" Poradnia Psychogeriatryczna

Sopot, Poland, 81-855

Osrodek Badan Klinicznych EUROMEDIS

Szczecin, Poland, 70-111

mMED Maciej Czarnecki

Warszawa, Poland, 01-697

Spain

Hospital General Universitario de Elche

Elche, Alicante, Spain, 3203

ALTHAIA Hospital Sant Joan de Deu

Manresa, Barcelona, Spain, 08243

Hospital Universitario Reina Sofía

Cordoba, Córdoba, Spain, 14011

Clinica Universidad de Navarra

Pamplona, Navarra, Spain, 31008

Hospital del Mar

Barcelona, Spain, 08003

Hospital Universitari Quiron Dexeus

Barcelona, Spain, 08028

Hospital Universitari de Bellvitge

Barcelona, Spain, 8907

Hospital Universitari Arnau de Vilanova

Lleida, Spain, 25198

Hospital Universitario Virgen Macarena

Sevilla, Spain, 41009

Sweden

Skånes Universitetssjukhus, Malmö

Malmö, Sweden, 20502

Sahlgrenska Universitetssjukhuset, Mölndal Sjukhus

Mölndal, Sweden, 43141

Karolinska Universitetssjukhuset, Huddinge

Stockholm, Sweden, 14186

Akademiska Sjukhuset

Uppsala, Sweden, 75185

Switzerland

Universitären Psychiatrischen Kliniken Basel (UPK)

Basel, Switzerland, 4025

Medizinisches Zentrum MZB Biel

Biel/Bienne, Switzerland, 2502

Hôpitaux Universitaires de Genève - HUG

Geneve 14, Switzerland, 1211

Centre Hospitalier Universitaire Vaudois

Lausanne, Switzerland, CH-1011

Ospedale Civico

Lugano, Switzerland, 6903

Institut fuer Regenerative Medizin (IREM) der Universitaet Zuerich, Zentrum fuer Praevention und Demenztherapie

Schlieren, Switzerland, 8952

Sponsors and Collaborators

Biogen

Investigators

• 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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Salloway 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.

• Responsible Party: Biogen
• ClinicalTrials.gov Identifier: NCT02484547
• Other Study ID Numbers: 221AD302; 2015-000967-15 ( EudraCT Number )
• First Posted: June 29, 2015
• Results First Posted: September 2, 2021
• Last Update Posted: September 2, 2021
• Last Verified: August 2021

Keywords provided by Biogen:

Aducanumab; BIIB037

Additional relevant MeSH terms:

Alzheimer Disease; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders