221AD301 Phase 3 Study of Aducanumab (BIIB037) in Early Alzheimer's Disease
- Registration Number
- NCT02477800
- Lead Sponsor
- Biogen
- 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) \[ADCS-ADL-MCI\].
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 1653
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Low Dose Aducanumab (BIIB037) Monthly intravenous (IV) infusion Low Dose Placebo Monthly intravenous (IV) infusion High Dose Aducanumab (BIIB037) Monthly intravenous (IV) infusion High Dose Placebo Monthly intravenous (IV) infusion
- Primary Outcome Measures
Name Time Method Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SB) Score at Week 78 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
Name Time Method Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (13 Items) (ADAS-Cog 13) Score at Week 78 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.
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 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.
Change From Baseline in Mini-Mental State Examination (MMSE) Score at Week 78 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.
Trial Locations
- Locations (155)
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Azienda Ospedaliero Universitaria Ospedali Riuniti
🇮🇹Torrette Di Ancona, Ancona, Italy
Centro Hospitalar e Universitário de Coimbra E.P.E
🇵🇹Coimbra, Portugal
Hospital Professor Doutor Fernando Fonseca, E.P.E.
🇵🇹Amadora, Portugal
Hospital de Braga
🇵🇹Braga, Portugal
CUF Alvalade
🇵🇹Lisboa, Portugal
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
Campus Neurologico Senior
🇵🇹Torres Vedras, Portugal
Kaohsiung Medical University Chung-Ho Memorial Hospital
🇨🇳Kaohsiung, Taiwan
University of Rochester
🇺🇸Rochester, New York, United States
Indiana University School of Medicine
🇺🇸Indianapolis, Indiana, United States
Via Christi Research, a division of Via Christi Hospitals Wichita, Inc.
🇺🇸Wichita, Kansas, United States
Neurodegenerative Disorders Research
🇦🇺West Perth, Western Australia, Australia
Albany Medical College
🇺🇸Albany, New York, United States
St. Joseph's Hospital and Medical Center
🇺🇸Phoenix, Arizona, United States
Lynn Health Science Institute
🇺🇸Oklahoma City, Oklahoma, United States
CCBR - Ballerup - DK
🇩🇰Ballerup, Denmark
Rigshospitalet
🇩🇰København Ø, Denmark
CCBR - Vejle - DK
🇩🇰Vejle, Denmark
Stobhill ACH Hospital
🇬🇧Glasgow, Strathclyde, United Kingdom
Neuropsychiatric Research Center of Southwest Florida
🇺🇸Fort Myers, Florida, United States
Azienda Ospedaliero Universitaria Pisana
🇮🇹Pisa, Italy
Torrance Clinical Research Institute, Inc.
🇺🇸Lomita, California, United States
Palm Beach Neurological Center
🇺🇸Palm Beach Gardens, Florida, United States
Azienda Ospedaliera Ospedali Riuniti di Bergamo
🇮🇹Bergamo, Italy
UCSF - Memory and Aging Center
🇺🇸San Francisco, California, United States
Georgetown University Hospital
🇺🇸Washington, District of Columbia, United States
Praxis Dr. med. Bergmann
🇩🇪Neuburg, Bayern, Germany
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
ANI Neurology, PLLC d/b/a Alzheimer's Memory Center
🇺🇸Charlotte, North Carolina, United States
Butler Hospital
🇺🇸Providence, Rhode Island, United States
Azienda Ospedaliero Universitaria San Martino
🇮🇹Genova, Italy
Policlinico Universitario Agostino Gemelli
🇮🇹Roma, Italy
Inha University Hospital
🇰🇷Incheon, Gyeonggi-do, Korea, Republic of
Universitaetsklinikum Aachen AOeR
🇩🇪Aachen, Nordrhein Westfalen, Germany
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Casa di Cura del Policlinico
🇮🇹Milano, Italy
Seconda Università degli Studi di Napoli
🇮🇹Napoli, Italy
Azienda Ospedaliera Universitaria OO. RR. S. Giovanni di Dio e Ruggi D'Aragona
🇮🇹Salerno, Italy
Konkuk University Medical Center
🇰🇷Seoul, Korea, Republic of
Policlinica Guipuzcoa
🇪🇸San Sebastian, Guipuzcoa, Spain
Central Coast Neurosciences Research, Gosford
🇦🇺East Gosford, New South Wales, Australia
Royal Brisbane and Women's Hospital
🇦🇺Herston, Queensland, Australia
Fundacio ACE
🇪🇸Barcelona, Spain
Gachon University Gil Medical Center
🇰🇷Incheon, Korea, Republic of
UT Southwestern Medical Center at Dallas
🇺🇸Dallas, Texas, United States
Azienda Ospedaliera Spedali Civili di Brescia
🇮🇹Brescia, Italy
Azienda Ospedaliera Universitaria "Federico II"
🇮🇹Napoli, Italy
A.O.U. Senese Policlinico Santa Maria alle Scotte
🇮🇹Siena, Italy
Fondazione Istituto G.Giglio di Cefalù
🇮🇹Cefalù, Palermo, Italy
ActivMed Practices & Research
🇺🇸Methuen, Massachusetts, United States
Charite Universitaetsmedizin Berlin - Campus Benjamin Franklin
🇩🇪Berlin, Germany
Research Site
🇯🇵Kodaira-shi, Japan
Chang Gung Memorial Hospital, Linkou
🇨🇳Taoyuan County, Taiwan
Kingshill Research Centre
🇬🇧Chippenham, Wiltshire, United Kingdom
Southmead Hospital
🇬🇧Bristol, Avon, United Kingdom
Re:Cognition Health Ltd
🇬🇧London, Greater London, United Kingdom
Salford Royal
🇬🇧Salford, Greater Manchester, United Kingdom
Manchester Royal Infirmary
🇬🇧Blackburn, Merseyside, United Kingdom
Newcastle University
🇬🇧Newcastle upon Tyne, Tyne & Wear, United Kingdom
Glasgow Memory Clinic Ltd
🇬🇧Glasgow, Strathclyde, United Kingdom
Neurologische Gemeinschaftspraxis Kassel
🇩🇪Kassel, Hessen, Germany
Universitaetsklinikum Bonn AoeR
🇩🇪Bonn, Nordrhein Westfalen, Germany
Hospital Universitario Dr. Peset
🇪🇸Valencia, Spain
Hospital Clinic i Provincial de Barcelona
🇪🇸Barcelona, Spain
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Toowoomba Base Hospital
🇦🇺Toowoomba, Queensland, Australia
Meridien Research
🇺🇸Tampa, Florida, United States
Stedman Clinical Trials, LLC
🇺🇸Tampa, Florida, United States
Raleigh Neurology Associates, P.A.
🇺🇸Raleigh, North Carolina, United States
Donald S. Marks, M.D., P.C.
🇺🇸Plymouth, Massachusetts, United States
Center for Neurosciences
🇺🇸Tucson, Arizona, United States
Senior Clinical Trials, Inc.
🇺🇸Laguna Hills, California, United States
California Neuroscience Research Medical Group Inc.
🇺🇸Sherman Oaks, California, United States
Brain Matters Research, Inc.
🇺🇸Delray Beach, Florida, United States
Compass Research Main
🇺🇸The Villages, Florida, United States
USF Health Byrd Institute
🇺🇸Tampa, Florida, United States
Premiere Research Institute
🇺🇸West Palm Beach, Florida, United States
Alexian Brothers Neurosciences Institute
🇺🇸Elk Grove Village, Illinois, United States
Fort Wayne Neurological Center
🇺🇸Fort Wayne, Indiana, United States
University of Kansas Medical Center Research Institute, Inc.
🇺🇸Kansas City, Kansas, United States
Baptist Health Lexington
🇺🇸Lexington, Kentucky, United States
Miami Jewish Health Systems
🇺🇸Miami, Florida, United States
Neurology Center of North Orange County
🇺🇸Fullerton, California, United States
University of California - Los Angeles
🇺🇸Los Angeles, California, United States
Jacksonville Center for Clinical Research
🇺🇸Jacksonville, Florida, United States
Southern California Research LLC
🇺🇸Simi Valley, California, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Clinical Neuroscience Solutions, Inc.
🇺🇸Memphis, Tennessee, United States
Cleveland Clinic Florida - Weston
🇺🇸Weston, Florida, United States
Brigham & Women's Hosp End/Dbt
🇺🇸Boston, Massachusetts, United States
Washington University
🇺🇸Saint 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
New York University Medical Center PRIME
🇺🇸New York, New York, 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
University of Tennessee Medical Center. Knoxville
🇺🇸Knoxville, Tennessee, United States
Neurology Clinic, PC
🇺🇸Cordova, Tennessee, United States
St Vincent's Hospital Sydney
🇦🇺Darlinghurst, New South Wales, Australia
Central Coast Neurosciences Research
🇦🇺Erina, New South Wales, Australia
Medical College of Wisconsin, Inc.
🇺🇸Milwaukee, Wisconsin, United States
Calvary Mater Newcastle
🇦🇺Waratah, New South Wales, Australia
KARA Institute for Neurological Diseases
🇦🇺North Ryde, New South Wales, Australia
The Prince Charles Hospital
🇦🇺Chermside, Queensland, Australia
CCBR - Ålborg - DK
🇩🇰Ålborg, Denmark
Heritage Medical Research Clinic
🇨🇦Calgary, Alberta, Canada
Toronto Sunnybrook Hospital
🇨🇦Toronto, Ontario, Canada
Toronto Memory Program (Neurology Research Inc.)
🇨🇦Toronto, Ontario, Canada
The Medical Arts Health Research Group
🇨🇦Penticton, British Columbia, Canada
The Montreal Neurological Institute
🇨🇦Montreal, Quebec, Canada
CHU de Quebec - Hôpital de l' Enfant Jésus
🇨🇦Quebec, Canada
McGill Centre for Studies in Aging
🇨🇦Verdun, Quebec, Canada
CHU Strasbourg - Hôpital Hautepierre
🇫🇷Strasbourg Cedex, Bas Rhin, France
Groupe Hospitalier Pellegrin - Hôpital Pellegrin
🇫🇷Bordeaux, Gironde, France
Hopital Louis Pasteur Colmar
🇫🇷Strasbourg, Bas Rhin, France
Hopital Neurologique Pierre Wertheimer
🇫🇷Bron Cedex, Rhone, France
Groupe hospitalier Broca - La Rochefoucauld - La Collégiale
🇫🇷Paris, France
Groupe Hospitalier Pitie-Salpetriere
🇫🇷Paris, France
Praxis Dr. Scholz
🇩🇪Boeblingen, Baden Wuerttemberg, Germany
Aerztliche Gemeinschaftspraxis
🇩🇪Ostfildern, Baden Wuerttemberg, Germany
Neuro MVZ Stuttgart
🇩🇪Stuttgart, Baden Wuerttemberg, Germany
Klinikum der Johann Wolfgang Goethe-Universitaet
🇩🇪Frankfurt, Bayern, Germany
Universitaetsklinikum Koeln
🇩🇪Cologne, Nordrhein Westfalen, Germany
Klinische Forschung Hannover-Mitte GmbH
🇩🇪Hannover, Niedersachsen, Germany
Ospedale San Raffaele
🇮🇹Milano, Italy
Hospital de Cruces
🇪🇸Barakaldo, Vizcaya, Spain
Clinica Ruber
🇪🇸Madrid, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital Universitari i Politecnic La Fe
🇪🇸Valencia, Spain
Changhua Christian Hospital
🇨🇳Changhua, Taiwan
The National Hospital for Neurology and Neurosurgery Centre
🇬🇧London, Greater London, United Kingdom
Ninewells Hospital
🇬🇧Dundee, Tayside Region, United Kingdom
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Gyeonggi-do, Korea, Republic of
Christian-Doppler-Klinik - Universitätsklinikum Salzburg
🇦🇹Salzburg, Austria
Advocate Lutheran General Hospital
🇺🇸Park Ridge, Illinois, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
LKH - Universitaetsklinikum Graz
🇦🇹Graz, Austria
CHU Reims - Hôpital Maison Blanche
🇫🇷Reims, Marne, France
Royal Melbourne Hospital
🇦🇺Parkville, Victoria, Australia
University of Miami
🇺🇸Miami, Florida, United States
UBC Hospital
🇨🇦Vancouver, British Columbia, Canada
Hospital Beatriz Ângelo
🇵🇹Loures, Portugal
Kaohsiung Chang Gung Memorial Hospital
🇨🇳Kaohsiung, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
The RICE Centre
🇬🇧Bath, Somerset, United Kingdom
The University of Edinburgh
🇬🇧Edinburgh, Lothian Region, United Kingdom
Institute for Neurodegenerative Disorders
🇺🇸New Haven, Connecticut, United States
Medical University of South Carolina (MUSC)
🇺🇸Charleston, South Carolina, United States
National Clinical Research Inc.-Richmond
🇺🇸Richmond, Virginia, United States
Box Hill Hospital
🇦🇺Box Hill, Victoria, Australia
Austin Hospital
🇦🇺Heidelberg, Victoria, Australia
Charing Cross Hospital
🇬🇧London, Greater London, United Kingdom