Clinical trial NCT02477800: 221AD301 Phase 3 Study of Aducanumab (BIIB037) in Early Alzheimer's Disease
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Alzheimer's Disease
Keywords: BIIB037
Aducanumab
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2015-06-23
Enrollment: 1653
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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) \[ADCS-ADL-MCI\].


Eligibility 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

Primary outcomes:
measure: Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SB) Score at Week 78
timeFrame: Baseline, Week 78
Secondary outcomes:
measure: Change From Baseline in Mini-Mental State Examination (MMSE) Score at Week 78
timeFrame: Baseline, Week 78
measure: Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (13 Items) (ADAS-Cog 13) Score at Week 78
timeFrame: Baseline, Week 78
measure: 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
timeFrame: Baseline, Week 78
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: St. Joseph's Hospital and Medical Center
state: Arizona
city: Tucson
country: United States
facility: Center for Neurosciences
state: Arizona
city: Fullerton
country: United States
facility: Neurology Center of North Orange County
state: California
city: Laguna Hills
country: United States
facility: Senior Clinical Trials, Inc.
state: California
city: Lomita
country: United States
facility: Torrance Clinical Research Institute, Inc.
state: California
city: Los Angeles
country: United States
facility: University of California - Los Angeles
state: California
city: San Francisco
country: United States
facility: UCSF - Memory and Aging Center
state: California
city: Sherman Oaks
country: United States
facility: California Neuroscience Research Medical Group Inc.
state: California
city: Simi Valley
country: United States
facility: Southern California Research LLC
state: California
city: New Haven
country: United States
facility: Institute for Neurodegenerative Disorders
state: Connecticut
city: Washington
country: United States
facility: Georgetown University Hospital
state: District of Columbia
city: Delray Beach
country: United States
facility: Brain Matters Research, Inc.
state: Florida
city: Fort Myers
country: United States
facility: Neuropsychiatric Research Center of Southwest Florida
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville Center for Clinical Research
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Miami
country: United States
facility: Miami Jewish Health Systems
state: Florida
city: Orlando
country: United States
facility: Compass Research Main
state: Florida
city: Palm Beach Gardens
country: United States
facility: Palm Beach Neurological Center
state: Florida
city: Tampa
country: United States
facility: Stedman Clinical Trials, LLC
state: Florida
city: Tampa
country: United States
facility: USF Health Byrd Institute
state: Florida
city: Tampa
country: United States
facility: Meridien Research
state: Florida
city: The Villages
country: United States
facility: Compass Research Main
state: Florida
city: West Palm Beach
country: United States
facility: Premiere Research Institute
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic Florida - Weston
state: Florida
city: Elk Grove Village
country: United States
facility: Alexian Brothers Neurosciences Institute
state: Illinois
city: Park Ridge
country: United States
facility: Advocate Lutheran General Hospital
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Neurological Center
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center Research Institute, Inc.
state: Kansas
city: Wichita
country: United States
facility: Via Christi Research, a division of Via Christi Hospitals Wichita, Inc.
state: Kansas
city: Lexington
country: United States
facility: Baptist Health Lexington
state: Kentucky
city: Boston
country: United States
facility: Brigham & Women's Hosp End/Dbt
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Methuen
country: United States
facility: ActivMed Practices & Research
state: Massachusetts
city: Plymouth
country: United States
facility: Donald S. Marks, M.D., P.C.
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Las Vegas
country: United States
facility: Las Vegas Medical research
state: Nevada
city: Toms River
country: United States
facility: Advanced Memory Research Institute of NJ, PC
state: New Jersey
city: Albany
country: United States
facility: Albany Medical College
state: New York
city: New York
country: United States
facility: New York University Medical Center PRIME
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Charlotte
country: United States
facility: ANI Neurology, PLLC d/b/a Alzheimer's Memory Center
state: North Carolina
city: Raleigh
country: United States
facility: Raleigh Neurology Associates, P.A.
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Oklahoma City
country: United States
facility: Lynn Health Science Institute
state: Oklahoma
city: Jenkintown
country: United States
facility: The Clinical Trial Center, LLC
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Plains
country: United States
facility: Northeastern Pennsylvania Memory and Alzheimer's Center
state: Pennsylvania
city: East Providence
country: United States
facility: Rhode Island Mood & Memory Research Institute
state: Rhode Island
city: Providence
country: United States
facility: Butler Hospital
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of South Carolina (MUSC)
state: South Carolina
city: Cordova
country: United States
facility: Neurology Clinic, PC
state: Tennessee
city: Knoxville
country: United States
facility: University of Tennessee Medical Center. Knoxville
state: Tennessee
city: Memphis
country: United States
facility: Clinical Neuroscience Solutions, Inc.
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern Medical Center at Dallas
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Richmond
country: United States
facility: National Clinical Research Inc.-Richmond
state: Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin, Inc.
state: Wisconsin
city: Darlinghurst
country: Australia
facility: St Vincent's Hospital Sydney
state: New South Wales
city: East Gosford
country: Australia
facility: Central Coast Neurosciences Research, Gosford
state: New South Wales
city: Erina
country: Australia
facility: Central Coast Neurosciences Research
state: New South Wales
city: North Ryde
country: Australia
facility: KARA Institute for Neurological Diseases
state: New South Wales
city: Waratah
country: Australia
facility: Calvary Mater Newcastle
state: New South Wales
city: Chermside
country: Australia
facility: The Prince Charles Hospital
state: Queensland
city: Herston
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: Toowoomba
country: Australia
facility: Toowoomba Base Hospital
state: Queensland
city: Box Hill
country: Australia
facility: Box Hill Hospital
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Hospital
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: West Perth
country: Australia
facility: Neurodegenerative Disorders Research
state: Western Australia
city: Graz
country: Austria
facility: LKH - Universitaetsklinikum Graz
city: Salzburg
country: Austria
facility: Christian-Doppler-Klinik - Universitätsklinikum Salzburg
city: Calgary
country: Canada
facility: Heritage Medical Research Clinic
state: Alberta
city: Penticton
country: Canada
facility: The Medical Arts Health Research Group
state: British Columbia
city: Vancouver
country: Canada
facility: UBC Hospital
state: British Columbia
city: Toronto
country: Canada
facility: Toronto Memory Program (Neurology Research Inc.)
state: Ontario
city: Toronto
country: Canada
facility: Toronto Sunnybrook Hospital
state: Ontario
city: Montreal
country: Canada
facility: The Montreal Neurological Institute
state: Quebec
city: Verdun
country: Canada
facility: McGill Centre for Studies in Aging
state: Quebec
city: Quebec
country: Canada
facility: CHU de Quebec - Hôpital de l' Enfant Jésus
city: Ballerup
country: Denmark
facility: CCBR - Ballerup - DK
city: København Ø
country: Denmark
facility: Rigshospitalet
city: Vejle
country: Denmark
facility: CCBR - Vejle - DK
city: Ålborg
country: Denmark
facility: CCBR - Ålborg - DK
city: Strasbourg Cedex
country: France
facility: CHU Strasbourg - Hôpital Hautepierre
state: Bas Rhin
city: Strasbourg
country: France
facility: Hopital Louis Pasteur Colmar
state: Bas Rhin
city: Bordeaux
country: France
facility: Groupe Hospitalier Pellegrin - Hôpital Pellegrin
state: Gironde
city: Reims
country: France
facility: CHU Reims - Hôpital Maison Blanche
state: Marne
city: Bron Cedex
country: France
facility: Hopital Neurologique Pierre Wertheimer
state: Rhone
city: Paris
country: France
facility: Groupe hospitalier Broca - La Rochefoucauld - La Collégiale
city: Paris
country: France
facility: Groupe Hospitalier Pitie-Salpetriere
city: Boeblingen
country: Germany
facility: Praxis Dr. Scholz
state: Baden Wuerttemberg
city: Ostfildern
country: Germany
facility: Aerztliche Gemeinschaftspraxis
state: Baden Wuerttemberg
city: Stuttgart
country: Germany
facility: Neuro MVZ Stuttgart
state: Baden Wuerttemberg
city: Frankfurt
country: Germany
facility: Klinikum der Johann Wolfgang Goethe-Universitaet
state: Bayern
city: Neuburg
country: Germany
facility: Praxis Dr. med. Bergmann
state: Bayern
city: Kassel
country: Germany
facility: Neurologische Gemeinschaftspraxis Kassel
state: Hessen
city: Hannover
country: Germany
facility: Klinische Forschung Hannover-Mitte GmbH
state: Niedersachsen
city: Aachen
country: Germany
facility: Universitaetsklinikum Aachen AOeR
state: Nordrhein Westfalen
city: Bonn
country: Germany
facility: Universitaetsklinikum Bonn AoeR
state: Nordrhein Westfalen
city: Cologne
country: Germany
facility: Universitaetsklinikum Koeln
state: Nordrhein Westfalen
city: Berlin
country: Germany
facility: Charite Universitaetsmedizin Berlin - Campus Benjamin Franklin
city: Torrette Di Ancona
country: Italy
facility: Azienda Ospedaliero Universitaria Ospedali Riuniti
state: Ancona
city: Cefalù
country: Italy
facility: Fondazione Istituto G.Giglio di Cefalù
state: Palermo
city: Bergamo
country: Italy
facility: Azienda Ospedaliera Ospedali Riuniti di Bergamo
city: Brescia
country: Italy
facility: Azienda Ospedaliera Spedali Civili di Brescia
city: Genova
country: Italy
facility: Azienda Ospedaliero Universitaria San Martino
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Milano
country: Italy
facility: Casa di Cura del Policlinico
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria "Federico II"
city: Napoli
country: Italy
facility: Seconda Università degli Studi di Napoli
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
city: Roma
country: Italy
facility: Policlinico Universitario Agostino Gemelli
city: Salerno
country: Italy
facility: Azienda Ospedaliera Universitaria OO. RR. S. Giovanni di Dio e Ruggi D'Aragona
city: Siena
country: Italy
facility: A.O.U. Senese Policlinico Santa Maria alle Scotte
city: Chiba-Shi
country: Japan
facility: Research Site
state: Chiba-Ken
city: Inzai-shi
country: Japan
facility: Research Site
state: Chiba-Ken
city: Kurume-shi
country: Japan
facility: Research Site
state: Fukuoka-ken
city: Aizuwakamatsu-shi
country: Japan
facility: Research Site
state: Fukushima-Ken
city: Asahikawa-shi
country: Japan
facility: Research Site
state: Hokkaido
city: Sapporo-shi
country: Japan
facility: Research Site
state: Hokkaido
city: Sapporo-shi
country: Japan
facility: Research Site
state: Hokkaido
city: Atsugi-shi
country: Japan
facility: Research Site
state: Kanagawa-Ken
city: Kamakura-shi
country: Japan
facility: Research Site
state: Kanagawa-Ken
city: Kawasaki-Shi
country: Japan
facility: Research Site
state: Kanagawa-Ken
city: Yokohama-shi
country: Japan
state: Kanagawa-ken
city: Yokohama-shi
country: Japan
facility: Research Site
state: Kanagawa-Ken
city: Yokohama-shi
country: Japan
facility: Research Site
state: Kanagawa-Ken
city: Kyoto-shi
country: Japan
facility: Research Site
state: Kyoto-Fu
city: Nagaoka-shi
country: Japan
facility: Research Site
state: Niigata-Ken
city: Iruma-gun
country: Japan
facility: Research Site
state: Saitama-Ken
city: Kasukabe-shi
country: Japan
facility: Research Site
state: Saitama-Ken
city: Bunkyo-ku
country: Japan
facility: Research Site
state: Tokyo-To
city: Shinjuku-ku (I)
country: Japan
facility: Research Site
state: Tokyo-To
city: Shinjuku-ku
country: Japan
facility: Research Site
state: Tokyo-To
city: Ota-ku
country: Japan
facility: Research Site
state: Tokyo
city: Yamagata-shi
country: Japan
facility: Research Site
state: Yamagata-Ken
city: Itabashi-ku
country: Japan
facility: Research Site
city: Itabashi-ku
country: Japan
facility: Research Site
city: Kiyose-shi
country: Japan
facility: Research Site
city: Kodaira-shi
country: Japan
facility: Research Site
city: Incheon
country: Korea, Republic of
facility: Inha University Hospital
state: Gyeonggi-do
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Konkuk University Medical Center
city: Amadora
country: Portugal
facility: Hospital Professor Doutor Fernando Fonseca, E.P.E.
city: Braga
country: Portugal
facility: Hospital de Braga
city: Coimbra
country: Portugal
facility: Centro Hospitalar e Universitário de Coimbra E.P.E
city: Lisboa
country: Portugal
facility: CUF Alvalade
city: Loures
country: Portugal
facility: Hospital Beatriz Ângelo
city: Torres Vedras
country: Portugal
facility: Campus Neurologico Senior
city: San Sebastian
country: Spain
facility: Policlinica Guipuzcoa
state: Guipuzcoa
city: Barakaldo
country: Spain
facility: Hospital de Cruces
state: Vizcaya
city: Barcelona
country: Spain
facility: Fundacio ACE
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Madrid
country: Spain
facility: Clinica Ruber
city: Valencia
country: Spain
facility: Hospital Universitario Dr. Peset
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
city: Changhua
country: Taiwan
facility: Changhua Christian Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taoyuan County
country: Taiwan
facility: Chang Gung Memorial Hospital, Linkou
city: Bristol
country: United Kingdom
facility: Southmead Hospital
state: Avon
city: London
country: United Kingdom
facility: Re:Cognition Health Ltd
state: Greater London
city: London
country: United Kingdom
facility: Charing Cross Hospital
state: Greater London
city: London
country: United Kingdom
facility: The National Hospital for Neurology and Neurosurgery Centre
state: Greater London
city: Salford
country: United Kingdom
facility: Salford Royal
state: Greater Manchester
city: Edinburgh
country: United Kingdom
facility: The University of Edinburgh
state: Lothian Region
city: Blackburn
country: United Kingdom
facility: Manchester Royal Infirmary
state: Merseyside
city: Bath
country: United Kingdom
facility: The RICE Centre
state: Somerset
city: Glasgow
country: United Kingdom
facility: Glasgow Memory Clinic Ltd
state: Strathclyde
city: Glasgow
country: United Kingdom
facility: Stobhill ACH Hospital
state: Strathclyde
city: Dundee
country: United Kingdom
facility: Ninewells Hospital
state: Tayside Region
city: Newcastle upon Tyne
country: United Kingdom
facility: Newcastle University
state: Tyne & Wear
city: Chippenham
country: United Kingdom
facility: Kingshill Research Centre
state: Wiltshire
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.