Clinical trial NCT02484547: 221AD302 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: Aducanumab
BIIB037
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2015-06-29
Enrollment: 1643
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 Scale - 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) 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: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Banner Alzheimer's Institute
state: Arizona
city: Phoenix
country: United States
facility: Xenoscience Inc.
state: Arizona
city: Sun City
country: United States
facility: Banner Sun Health Research Institute
state: Arizona
city: Irvine
country: United States
facility: Institute for Memory Impairments
state: California
city: Long Beach
country: United States
facility: Renewal Behavioral Health
state: California
city: Los Angeles
country: United States
facility: USC Keck School of Medicine
state: California
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital Presbyterian
state: California
city: Oceanside
country: United States
facility: Excell Research, Inc.
state: California
city: Oxnard
country: United States
facility: Pacific Neuroscience Medical Group
state: California
city: Redlands
country: United States
facility: Anderson Clinical Research
state: California
city: San Diego
country: United States
facility: Pacific Research Network
state: California
city: San Diego
country: United States
facility: University of California San Diego Medical Center
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: Santa Ana
country: United States
facility: Syrentis Clinical Research
state: California
city: Santa Rosa
country: United States
facility: St Joseph Heritage Healthcare
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Aurora
country: United States
facility: University Of Colorado Denver
state: Colorado
city: Thornton
country: United States
facility: IMMUNOe International Research Centers
state: Colorado
city: Fairfield
country: United States
facility: Associated Neurologists of Southern Connecticut, PC
state: Connecticut
city: New Haven
country: United States
facility: Yale University School Of Medicine
state: Connecticut
city: Norwalk
country: United States
facility: Research Center for Clinical Studies, Inc.
state: Connecticut
city: Atlantis
country: United States
facility: JEM Research Institute
state: Florida
city: Bradenton
country: United States
facility: Bradenton Research Center, Inc.
state: Florida
city: Brooksville
country: United States
facility: Meridien Research
state: Florida
city: Deerfield Beach
country: United States
facility: Quantum Laboratories Inc.
state: Florida
city: Hollywood
country: United States
facility: Infinity Clinical Research, LLC
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic in Florida
state: Florida
city: Ocala
country: United States
facility: Renstar Medical Research
state: Florida
city: Orlando
country: United States
facility: Clinical Neuroscience Solutions, Inc.
state: Florida
city: Tampa
country: United States
facility: Axiom Clinical Research of Florida
state: Florida
city: Atlanta
country: United States
facility: Emory University Cognitive Neurology Clinic & ADRC
state: Georgia
city: Columbus
country: United States
facility: Medical Research Health and Education Foundation, Inc
state: Georgia
city: Decatur
country: United States
facility: NeuroStudies.net, LLC
state: Georgia
city: Indianapolis
country: United States
facility: Josephson, Wallack, Munshower Neurology, PC
state: Indiana
city: Belmont
country: United States
facility: McLean Hospital
state: Massachusetts
city: Newton
country: United States
facility: Boston Center for Memory
state: Massachusetts
city: Hattiesburg
country: United States
facility: Hattiesburg Clinic, PA
state: Mississippi
city: Las Vegas
country: United States
facility: Cleveland Clinic Lou Ruvo Center for Brain Health
state: Nevada
city: Portsmouth
country: United States
facility: ActivMed Practices & Research
state: New Hampshire
city: Lawrenceville
country: United States
facility: AdvanceMed Research
state: New Jersey
city: Latham
country: United States
facility: Empire Neurology, PC
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College-New York Presbyterian Hospital
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Winston-Salem
country: United States
facility: PMG Research of Winston-Salem, LLC
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
city: Dublin
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Allentown
country: United States
facility: Lehigh Center for Clinical Research, LLC
state: Pennsylvania
city: Philadelphia
country: United States
facility: Penn Memory Center
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: North Charleston
country: United States
facility: Roper St. Francis Healthcare
state: South Carolina
city: Austin
country: United States
facility: Senior Adult Specialty Research
state: Texas
city: Houston
country: United States
facility: The Methodist Hospital Research Institute
state: Texas
city: Houston
country: United States
facility: Clinical Trial Network
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Health Sciences Center
state: Utah
city: Bennington
country: United States
facility: Clinical Neuroscience Research Association, Inc
state: Vermont
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Spokane
country: United States
facility: Northwest Neurological, PLLC
state: Washington
city: Brasschaat
country: Belgium
facility: A.Z. Klina
city: Brugge
country: Belgium
facility: AZ Sint-Jan Brugge
city: Bruxelles
country: Belgium
facility: Universitair Ziekenhuis Brussel
city: Fraiture
country: Belgium
facility: Centre Neurologique & de Réadaptation Fonctionnelle
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Kortrijk
country: Belgium
facility: AZ Groeninge - Campus Kennedylaan
city: Leuven
country: Belgium
facility: UZ Leuven
city: Roeselare
country: Belgium
facility: AZ Delta
city: Kamloops
country: Canada
facility: Health Research.
state: British Columbia
city: West Vancouver
country: Canada
facility: Health Research
state: British Columbia
city: Halifax
country: Canada
facility: True North Clinical Research - Halifax Inc.
state: Nova Scotia
city: Kentville
country: Canada
facility: True North Clinical Research Kentville, Inc
state: Nova Scotia
city: Burlington
country: Canada
facility: JBN Medical Diagnostic Services Inc.
state: Ontario
city: London
country: Canada
facility: St. Joseph's HC- Parkwood Institute
state: Ontario
city: Ottawa
country: Canada
facility: Bruyere Continuing Care
state: Ontario
city: Peterborough
country: Canada
facility: Kawartha Regional Memory Clinic
state: Ontario
city: Toronto
country: Canada
facility: Toronto Western Hospital
state: Ontario
city: Gatineau
country: Canada
facility: Recherches Neuro-Hippocampe Inc.
state: Quebec
city: Greenfield Park
country: Canada
facility: Recherche Sepmus, Inc.
state: Quebec
city: Sherbrooke
country: Canada
facility: DIEX Recherche Sherbrooke Inc.
state: Quebec
city: Verdun
country: Canada
facility: Douglas Hospital Research Centre
state: Quebec
city: Helsinki
country: Finland
facility: Terveystalo Kamppi
city: Kuopio
country: Finland
facility: Itä-Suomen yliopisto, Aivotutkimusyksikkö
city: Turku
country: Finland
facility: CRST, Clinical Research Services Turku
city: Marseille
country: France
facility: Hôpital de la Timone
state: Bouches-du-Rhône
city: Toulouse cedex 9
country: France
facility: CHU de Toulouse - Hôpital Purpan
state: Haute Garonne
city: Toulouse
country: France
facility: Centre de Recherche Clinique du Gérontopôle - Cité de la Santé
state: Haute Garonne
city: Montpellier
country: France
facility: Hôpital Gui de Chauliac
state: Herault
city: Rennes cedex 09
country: France
facility: CHU Rennes - Hopital Pontchaillou
state: Ille Et Vilaine
city: Nantes cedex 1
country: France
facility: CHU Nantes - Hopital Nord Laënnec
state: Loire Atlantique
city: Lille Cedex
country: France
facility: Hopital Roger Salengro - CHU Lille
state: Nord
city: Villeurbanne
country: France
facility: Hôpital des Charpennes
state: Rhone
city: Paris
country: France
facility: Hôpital Fernand Widal
city: Gunzburg
country: Germany
facility: Bezirkskrankenhaus Guenzburg
state: Baden Wuerttemberg
city: Mannheim
country: Germany
facility: ISPG - Institut fuer Studien zur Psychischen Gesundheit
state: Baden Wuerttemberg
city: Ulm
country: Germany
facility: Nervenfachaerztlichen Gemeinschaftspraxis Ulm
state: Baden Wuerttemberg
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm
state: Baden Wuerttemberg
city: Bayreuth
country: Germany
facility: Klinik Hohe Warte Bayreuth
state: Bayern
city: Muenchen
country: Germany
facility: Institut fuer Schlaganfall- und Demenzforschung (ISD)
state: Bayern
city: Muenchen
country: Germany
facility: Klinikum rechts der Isar der TU Muenchen
state: Bayern
city: Unterhaching
country: Germany
facility: Neuropraxis Muenchen Sued
state: Bayern
city: Erbach
country: Germany
facility: Neuro Centrum Odenwald
state: Hessen
city: Duesseldorf
country: Germany
facility: Universitaetsklinikum Duesseldorf AoeR
state: Nordrhein Westfalen
city: Muenster
country: Germany
facility: Universitaetsklinikum Muenster
state: Nordrhein Westfalen
city: Siegen
country: Germany
facility: Zentrum f. Neurologisch- Psychiatrische Studien und Begutachtung
state: Nordrhein Westfalen
city: Bielefeld
country: Germany
facility: Schwerpunktpraxis fuer Neurologie, Psychiatrie und Klinische Studien
state: North Rhine-Westphalia
city: Mainz
country: Germany
facility: Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
state: Rheinland Pfalz
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz gGmbH
state: Sachsen
city: Leipzig
country: Germany
facility: Kopfzentrum Leipzig
state: Sachsen
city: Altenburg
country: Germany
facility: Klinikum Altenburger Land GmbH
state: Thueringen
city: Berlin
country: Germany
facility: emovis GmbH
city: Berlin
country: Germany
facility: Neurologie im Tempelhofer Hafen
city: Ponderano
country: Italy
facility: Ospedale degli Infermi
state: Biella
city: Tricase
country: Italy
facility: Azienda Ospedaliera Card. G. Panico
state: Lecce
city: Monza
country: Italy
facility: ASST di Monza
state: Milano
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Neurologico Carlo Besta
city: Palermo
country: Italy
facility: Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone
city: Perugia
country: Italy
facility: Azienda Ospedaliera di Perugia Ospedale S. Maria della Misericordia
city: Roma
country: Italy
facility: Fondazione Santa Lucia IRCCS
city: Roma
country: Italy
facility: Umberto I Pol. di Roma-Università di Roma La Sapienza
city: Obu-shi
country: Japan
facility: Research Site
state: Aichi-Ken
city: Toon-shi
country: Japan
facility: Research Site
state: Ehime-Ken
city: Fukuoka-shi
country: Japan
facility: Research Site
state: Fukuoka-Ken
city: Kurume-shi
country: Japan
facility: Research Site
state: Fukuoka-Ken
city: Otake-shi
country: Japan
facility: Research Site
state: Hiroshima-Ken
city: Amagasaki-shi
country: Japan
facility: Research Site
state: Hyogo-Ken
city: Himeji-shi
country: Japan
facility: Research site
state: Hyogo-Ken
city: Himeji-shi
country: Japan
facility: Research Site
state: Hyogo-Ken
city: Kobe-shi
country: Japan
facility: Research Site
state: Hyogo-Ken
city: Kita-gun
country: Japan
facility: Research Site
state: Kagawa-Ken
city: Kyoto-shi
country: Japan
facility: Research Site
state: Kyoto-Fu
city: Kyoto-shi
country: Japan
facility: Research Site
state: Kyoto-Fu
city: Tsu-shi
country: Japan
facility: Research Site
state: Mie-Ken
city: Nishisonogi
country: Japan
facility: Research Site
state: Nagasaki-Ken
city: Yufu-shi
country: Japan
facility: Research Site
state: Oita-Ken
city: Kurashiki-shi
country: Japan
facility: Research Site
state: Okayama-Ken
city: Okayama-shi
country: Japan
facility: Research Site
state: Okayama-Ken
city: Tsukuba-gun
country: Japan
facility: Research Site
state: Okayama-Ken
city: Kishiwada-shi
country: Japan
facility: Research Site
state: Osaka-Fu
city: Osaka-shi
country: Japan
facility: Research Site
state: Osaka-Fu
city: Osaka-shi
country: Japan
facility: Research Site
state: Osaka-Fu
city: Osaka-shi
country: Japan
facility: Research Site
state: Osaka-Fu
city: Sennan-shi
country: Japan
facility: Research Site
state: Osaka-Fu
city: Suita-shi
country: Japan
facility: Research Site
state: Osaka-Fu
city: Iwata-shi
country: Japan
facility: Research Site
state: Shizuoka-Ken
city: Shizuoka-shi
country: Japan
facility: Research Site
state: Shizuoka-Ken
city: Shizuoka-shi
country: Japan
facility: Research Site
state: Shizuoka-Ken
city: Amsterdam
country: Netherlands
facility: Alzheimer Research Center
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum
city: Bialystok
country: Poland
facility: Podlaskie Centrum Psychogeriatrii
city: Bydgoszcz
country: Poland
facility: PALLMED Sp. z o.o.
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Katowice
country: Poland
facility: Novo-Med Zielinski i wspolnicy Sp. j.
city: Lodz
country: Poland
facility: SPZOZ Centralny Szpital Kliniczny UM w Lodzi
city: Lubin
country: Poland
facility: Centrum Diagnostyczno - Terapeutyczne "MEDICUS" Sp.z o.o.
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie
city: Plewiska
country: Poland
facility: Neurologiczny NZOZ Centrum Leczenia SM
city: Poznan
country: Poland
facility: NZOZ "NEURO-KARD", "Ilkowski i Partnerzy" Sp. Partn. Lek.
city: Rzeszow
country: Poland
facility: Centrum Medyczne Medyk
city: Slaskie
country: Poland
facility: Neuro-Care Gabriela Klodowska
city: Sopot
country: Poland
facility: NZOZ "SENIOR" Poradnia Psychogeriatryczna
city: Szczecin
country: Poland
facility: Osrodek Badan Klinicznych EUROMEDIS
city: Warszawa
country: Poland
facility: mMED Maciej Czarnecki
city: Elche
country: Spain
facility: Hospital General Universitario de Elche
state: Alicante
city: Manresa
country: Spain
facility: ALTHAIA Hospital Sant Joan de Deu
state: Barcelona
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofía
state: Córdoba
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
state: Navarra
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Universitari Quiron Dexeus
city: Barcelona
country: Spain
facility: Hospital Universitari de Bellvitge
city: Lleida
country: Spain
facility: Hospital Universitari Arnau de Vilanova
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Malmö
country: Sweden
facility: Skånes Universitetssjukhus, Malmö
city: Mölndal
country: Sweden
facility: Sahlgrenska Universitetssjukhuset, Mölndal Sjukhus
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset, Huddinge
city: Uppsala
country: Sweden
facility: Akademiska Sjukhuset
city: Basel
country: Switzerland
facility: Universitären Psychiatrischen Kliniken Basel (UPK)
city: Biel/Bienne
country: Switzerland
facility: Medizinisches Zentrum MZB Biel
city: Geneve 14
country: Switzerland
facility: Hôpitaux Universitaires de Genève - HUG
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: Lugano
country: Switzerland
facility: Ospedale Civico
city: Schlieren
country: Switzerland
facility: Institut fuer Regenerative Medizin (IREM) der Universitaet Zuerich, Zentrum fuer Praevention und Demenztherapie
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.