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

Alzheimer's Disease Clinical Trial

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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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02477800
• Other study ID #: 221AD301
• Secondary ID: 2015-000966-72
• Status: Terminated
• Phase: Phase 3
• Start date: August 13, 2015
• Est. completion date: August 8, 2019

Study information

• Verified date: August 2021
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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].

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1653
• Est. completion date: August 8, 2019
• Est. primary completion date: August 8, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

Drug:
• Aducanumab (BIIB037)
Low dose
• Aducanumab (BIIB037)
High dose
• Placebo
Placebo

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Canada,  Denmark,  France,  Germany,  Italy,  Japan,  Korea, Republic of,  Portugal,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Clinical Dementia Rating 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	Change From Baseline in Mini-Mental State Examination (MMSE) Score at 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.	Baseline, Week 78
Secondary	Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (13 Items) (ADAS-Cog 13) Score at 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.	Baseline, Week 78
Secondary	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	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.	Baseline, Week 78