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

NCT ID: NCT02477800

Last Updated: 2021-09-02

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 1653 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-08-13
• Study Completion Date: 2019-08-08

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].

Conditions

Alzheimer's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Low Dose

Monthly intravenous (IV) infusion

Group Type: EXPERIMENTAL

Aducanumab (BIIB037)

Intervention Type: DRUG

Low dose

Placebo

Intervention Type: DRUG

Placebo

High Dose

Monthly intravenous (IV) infusion

Group Type: EXPERIMENTAL

Aducanumab (BIIB037)

Intervention Type: DRUG

High dose

Placebo

Intervention Type: DRUG

Placebo

Interventions

Aducanumab (BIIB037)

Low dose

Intervention Type: DRUG

Aducanumab (BIIB037)

High dose

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

Eligibility Criteria

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

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)

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Biogen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Biogen

Locations

St. Joseph's Hospital and Medical Center

Phoenix, Arizona, United States

Center for Neurosciences

Tucson, Arizona, United States

Neurology Center of North Orange County

Fullerton, California, United States

Senior Clinical Trials, Inc.

Laguna Hills, California, United States

Torrance Clinical Research Institute, Inc.

Lomita, California, United States

University of California - Los Angeles

Los Angeles, California, United States

UCSF - Memory and Aging Center

San Francisco, California, United States

California Neuroscience Research Medical Group Inc.

Sherman Oaks, California, United States

Southern California Research LLC

Simi Valley, California, United States

Institute for Neurodegenerative Disorders

New Haven, Connecticut, United States

Georgetown University Hospital

Washington D.C., District of Columbia, United States

Brain Matters Research, Inc.

Delray Beach, Florida, United States

Neuropsychiatric Research Center of Southwest Florida

Fort Myers, Florida, United States

Jacksonville Center for Clinical Research

Jacksonville, Florida, United States

University of Miami

Miami, Florida, United States

Miami Jewish Health Systems

Miami, Florida, United States

Compass Research Main

Orlando, Florida, United States

Palm Beach Neurological Center

Palm Beach Gardens, Florida, United States

Stedman Clinical Trials, LLC

Tampa, Florida, United States

USF Health Byrd Institute

Tampa, Florida, United States

Meridien Research

Tampa, Florida, United States

Compass Research Main

The Villages, Florida, United States

Premiere Research Institute

West Palm Beach, Florida, United States

Cleveland Clinic Florida - Weston

Weston, Florida, United States

Alexian Brothers Neurosciences Institute

Elk Grove Village, Illinois, United States

Advocate Lutheran General Hospital

Park Ridge, Illinois, United States

Fort Wayne Neurological Center

Fort Wayne, Indiana, United States

Indiana University School of Medicine

Indianapolis, Indiana, United States

University of Kansas Medical Center Research Institute, Inc.

Kansas City, Kansas, United States

Via Christi Research, a division of Via Christi Hospitals Wichita, Inc.

Wichita, Kansas, United States

Baptist Health Lexington

Lexington, Kentucky, United States

Brigham & Women's Hosp End/Dbt

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

ActivMed Practices & Research

Methuen, Massachusetts, United States

Donald S. Marks, M.D., P.C.

Plymouth, Massachusetts, United States

Mayo Clinic

Rochester, Minnesota, United States

Washington University

St Louis, Missouri, United States

Las Vegas Medical research

Las Vegas, Nevada, United States

Advanced Memory Research Institute of NJ, PC

Toms River, New Jersey, United States

Albany Medical College

Albany, New York, United States

New York University Medical Center PRIME

New York, New York, United States

University of Rochester

Rochester, New York, United States

ANI Neurology, PLLC d/b/a Alzheimer's Memory Center

Charlotte, North Carolina, United States

Raleigh Neurology Associates, P.A.

Raleigh, North Carolina, United States

Cleveland Clinic

Cleveland, Ohio, United States

Lynn Health Science Institute

Oklahoma City, Oklahoma, United States

The Clinical Trial Center, LLC

Jenkintown, Pennsylvania, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Northeastern Pennsylvania Memory and Alzheimer's Center

Plains, Pennsylvania, United States

Rhode Island Mood & Memory Research Institute

East Providence, Rhode Island, United States

Butler Hospital

Providence, Rhode Island, United States

Medical University of South Carolina (MUSC)

Charleston, South Carolina, United States

Neurology Clinic, PC

Cordova, Tennessee, United States

University of Tennessee Medical Center. Knoxville

Knoxville, Tennessee, United States

Clinical Neuroscience Solutions, Inc.

Memphis, Tennessee, United States

UT Southwestern Medical Center at Dallas

Dallas, Texas, United States

Baylor College of Medicine

Houston, Texas, United States

National Clinical Research Inc.-Richmond

Richmond, Virginia, United States

Medical College of Wisconsin, Inc.

Milwaukee, Wisconsin, United States

St Vincent's Hospital Sydney

Darlinghurst, New South Wales, Australia

Central Coast Neurosciences Research, Gosford

East Gosford, New South Wales, Australia

Central Coast Neurosciences Research

Erina, New South Wales, Australia

KARA Institute for Neurological Diseases

North Ryde, New South Wales, Australia

Calvary Mater Newcastle

Waratah, New South Wales, Australia

The Prince Charles Hospital

Chermside, Queensland, Australia

Royal Brisbane and Women's Hospital

Herston, Queensland, Australia

Toowoomba Base Hospital

Toowoomba, Queensland, Australia

Box Hill Hospital

Box Hill, Victoria, Australia

Austin Hospital

Heidelberg, Victoria, Australia

Royal Melbourne Hospital

Parkville, Victoria, Australia

Neurodegenerative Disorders Research

West Perth, Western Australia, Australia

LKH - Universitaetsklinikum Graz

Graz, , Austria

Christian-Doppler-Klinik - Universitätsklinikum Salzburg

Salzburg, , Austria

Heritage Medical Research Clinic

Calgary, Alberta, Canada

The Medical Arts Health Research Group

Penticton, British Columbia, Canada

UBC Hospital

Vancouver, British Columbia, Canada

Toronto Memory Program (Neurology Research Inc.)

Toronto, Ontario, Canada

Toronto Sunnybrook Hospital

Toronto, Ontario, Canada

The Montreal Neurological Institute

Montreal, Quebec, Canada

McGill Centre for Studies in Aging

Verdun, Quebec, Canada

CHU de Quebec - Hôpital de l' Enfant Jésus

Québec, , Canada

CCBR - Ålborg - DK

Aalborg, , Denmark

CCBR - Ballerup - DK

Ballerup Municipality, , Denmark

Rigshospitalet

København Ø, , Denmark

CCBR - Vejle - DK

Vejle, , Denmark

Hopital Louis Pasteur Colmar

Strasbourg, Bas Rhin, France

CHU Strasbourg - Hôpital Hautepierre

Strasbourg, Bas Rhin, France

Groupe Hospitalier Pellegrin - Hôpital Pellegrin

Bordeaux, Gironde, France

CHU Reims - Hôpital Maison Blanche

Reims, Marne, France

Hopital Neurologique Pierre Wertheimer

Bron, Rhone, France

Groupe hospitalier Broca - La Rochefoucauld - La Collégiale

Paris, , France

Groupe Hospitalier Pitie-Salpetriere

Paris, , France

Praxis Dr. Scholz

Böblingen, Baden-Wurttemberg, Germany

Aerztliche Gemeinschaftspraxis

Ostfildern, Baden-Wurttemberg, Germany

Neuro MVZ Stuttgart

Stuttgart, Baden-Wurttemberg, Germany

Klinikum der Johann Wolfgang Goethe-Universitaet

Frankfurt, Bavaria, Germany

Praxis Dr. med. Bergmann

Neuburg am Inn, Bavaria, Germany

Neurologische Gemeinschaftspraxis Kassel

Kassel, Hesse, Germany

Klinische Forschung Hannover-Mitte GmbH

Hanover, Lower Saxony, Germany

Universitaetsklinikum Aachen AOeR

Aachen, North Rhine-Westphalia, Germany

Universitaetsklinikum Bonn AoeR

Bonn, North Rhine-Westphalia, Germany

Universitaetsklinikum Koeln

Cologne, North Rhine-Westphalia, Germany

Charite Universitaetsmedizin Berlin - Campus Benjamin Franklin

Berlin, , Germany

Azienda Ospedaliero Universitaria Ospedali Riuniti

Torrette Di Ancona, Ancona, Italy

Fondazione Istituto G.Giglio di Cefalù

Cefalù, Palermo, Italy

Azienda Ospedaliera Ospedali Riuniti di Bergamo

Bergamo, , Italy

Azienda Ospedaliera Spedali Civili di Brescia

Brescia, , Italy

Azienda Ospedaliero Universitaria San Martino

Genova, , Italy

Ospedale San Raffaele

Milan, , Italy

Casa di Cura del Policlinico

Milan, , Italy

Azienda Ospedaliera Universitaria "Federico II"

Napoli, , Italy

Seconda Università degli Studi di Napoli

Napoli, , Italy

Azienda Ospedaliero Universitaria Pisana

Pisa, , Italy

Policlinico Universitario Agostino Gemelli

Roma, , Italy

Azienda Ospedaliera Universitaria OO. RR. S. Giovanni di Dio e Ruggi D'Aragona

Salerno, , Italy

A.O.U. Senese Policlinico Santa Maria alle Scotte

Siena, , Italy

Research Site

Chiba, Chiba, Japan

Research Site

Inzai-shi, Chiba, Japan

Research Site

Kurume-shi, Fukuoka, Japan

Research Site

Aizuwakamatsu-shi, Fukushima, Japan

Research Site

Asahikawa-shi, Hokkaido, Japan

Research Site

Sapporo, Hokkaido, Japan

Research Site

Sapporo, Hokkaido, Japan

Research Site

Atsugi-shi, Kanagawa, Japan

Research Site

Kamakura-shi, Kanagawa, Japan

Research Site

Kawasaki-Shi, Kanagawa, Japan

Yokohama, Kanagawa, Japan

Research Site

Yokohama, Kanagawa, Japan

Research Site

Yokohama, Kanagawa, Japan

Research Site

Kyoto, Kyoto, Japan

Research Site

Nagaoka-shi, Niigata, Japan

Research Site

Iruma-gun, Saitama, Japan

Research Site

Kasukabe-shi, Saitama, Japan

Research Site

Ōta-ku, Tokyo, Japan

Research Site

Bunkyō City, Tokyo-To, Japan

Research Site

Shinjuku-ku (I), Tokyo-To, Japan

Research Site

Shinjuku-ku, Tokyo-To, Japan

Research Site

Yamagata, Yamagata, Japan

Research Site

Itabashi-ku, , Japan

Research Site

Itabashi-ku, , Japan

Research Site

Kiyose-shi, , Japan

Research Site

Kodaira-shi, , Japan

Hospital Professor Doutor Fernando Fonseca, E.P.E.

Amadora, , Portugal

Hospital de Braga

Braga, , Portugal

Centro Hospitalar e Universitário de Coimbra E.P.E

Coimbra, , Portugal

CUF Alvalade

Lisbon, , Portugal

Hospital Beatriz Ângelo

Loures, , Portugal

Campus Neurologico Senior

Torres Vedras, , Portugal

Inha University Hospital

Incheon, Gyeonggi-do, South Korea

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, South Korea

Gachon University Gil Medical Center

Incheon, , South Korea

Asan Medical Center

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Konkuk University Medical Center

Seoul, , South Korea

Policlinica Guipuzcoa

Donostia / San Sebastian, Guipuzcoa, Spain

Hospital de Cruces

Barakaldo, Vizcaya, Spain

Fundacio ACE

Barcelona, , Spain

Hospital Clinic i Provincial de Barcelona

Barcelona, , Spain

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Clinica Ruber

Madrid, , Spain

Hospital Universitario Dr. Peset

Valencia, , Spain

Hospital Universitari i Politecnic La Fe

Valencia, , Spain

Changhua Christian Hospital

Changhua, , Taiwan

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, , Taiwan

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, , Taiwan

National Cheng Kung University Hospital

Tainan City, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Chang Gung Memorial Hospital, Linkou

Taoyuan, , Taiwan

Southmead Hospital

Bristol, Avon, United Kingdom

Re:Cognition Health Ltd

London, Greater London, United Kingdom

Charing Cross Hospital

London, Greater London, United Kingdom

The National Hospital for Neurology and Neurosurgery Centre

London, Greater London, United Kingdom

Salford Royal

Salford, Greater Manchester, United Kingdom

The University of Edinburgh

Edinburgh, Lothian Region, United Kingdom

Manchester Royal Infirmary

Blackburn, Merseyside, United Kingdom

The RICE Centre

Bath, Somerset, United Kingdom

Glasgow Memory Clinic Ltd

Glasgow, Strathclyde, United Kingdom

Stobhill ACH Hospital

Glasgow, Strathclyde, United Kingdom

Ninewells Hospital

Dundee, Tayside Region, United Kingdom

Newcastle University

Newcastle upon Tyne, Tyne & Wear, United Kingdom

Kingshill Research Centre

Chippenham, Wiltshire, United Kingdom

Countries

United States; Australia; Austria; Canada; Denmark; France; Germany; Italy; Japan; Portugal; South Korea; Spain; Taiwan; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 38165296 (View on PubMed)

Muralidharan 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.

Reference Type: DERIVED

PMID: 36600109 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34807243 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2015-000966-72

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

221AD301

Identifier Type: -

Identifier Source: org_study_id