221AD302 Phase 3 Study of Aducanumab (BIIB037) in Early Alzheimer's Disease
- Registration Number
- NCT02484547
- 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
- 1643
- 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) infusions Low Dose Placebo Monthly intravenous (IV) infusions High Dose Aducanumab (BIIB037) Monthly intravenous (IV) infusions High Dose Placebo Monthly intravenous (IV) infusions
- Primary Outcome Measures
Name Time Method Change From Baseline in Clinical Dementia Rating Scale - 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 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.
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 Alzheimer's Disease Assessment Scale-Cognitive Subscale (13 Items) (ADAS-Cog 13) 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.
Trial Locations
- Locations (155)
Lehigh Center for Clinical Research, LLC
🇺🇸Allentown, Pennsylvania, United States
Syrentis Clinical Research
🇺🇸Santa Ana, California, United States
Hattiesburg Clinic, PA
🇺🇸Hattiesburg, Mississippi, United States
Roper St. Francis Healthcare
🇺🇸North Charleston, South Carolina, United States
Toronto Western Hospital
🇨🇦Toronto, Ontario, Canada
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
Hôpital de la Timone
🇫🇷Marseille, Bouches-du-Rhône, France
University of California San Diego Medical Center
🇺🇸San Diego, California, United States
California Pacific Medical Center
🇺🇸San Francisco, California, United States
Josephson, Wallack, Munshower Neurology, PC
🇺🇸Indianapolis, Indiana, United States
Clinical Trial Network
🇺🇸Houston, Texas, United States
USC Keck School of Medicine
🇺🇸Los Angeles, California, United States
Banner Alzheimer's Institute
🇺🇸Phoenix, Arizona, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Zentrum f. Neurologisch- Psychiatrische Studien und Begutachtung
🇩🇪Siegen, Nordrhein Westfalen, Germany
St Joseph Heritage Healthcare
🇺🇸Santa Rosa, California, United States
AdvanceMed Research
🇺🇸Lawrenceville, New Jersey, United States
Emory University Cognitive Neurology Clinic & ADRC
🇺🇸Atlanta, Georgia, United States
Xenoscience Inc.
🇺🇸Phoenix, Arizona, United States
Banner Sun Health Research Institute
🇺🇸Sun City, Arizona, United States
Renewal Behavioral Health
🇺🇸Long Beach, California, United States
Excell Research, Inc.
🇺🇸Oceanside, California, United States
Anderson Clinical Research
🇺🇸Redlands, California, United States
Hoag Memorial Hospital Presbyterian
🇺🇸Newport Beach, California, United States
Pacific Research Network
🇺🇸San Diego, California, United States
IMMUNOe International Research Centers
🇺🇸Thornton, Colorado, United States
Stanford University Medical Center
🇺🇸Stanford, California, United States
Research Center for Clinical Studies, Inc.
🇺🇸Norwalk, Connecticut, United States
JEM Research Institute
🇺🇸Atlantis, Florida, United States
Bradenton Research Center, Inc.
🇺🇸Bradenton, Florida, United States
Renstar Medical Research
🇺🇸Ocala, Florida, United States
Mayo Clinic in Florida
🇺🇸Jacksonville, Florida, United States
Medical Research Health and Education Foundation, Inc
🇺🇸Columbus, Georgia, United States
McLean Hospital
🇺🇸Belmont, Massachusetts, United States
Boston Center for Memory
🇺🇸Newton, Massachusetts, United States
NeuroStudies.net, LLC
🇺🇸Decatur, Georgia, United States
Empire Neurology, PC
🇺🇸Latham, New York, United States
ActivMed Practices & Research
🇺🇸Portsmouth, New Hampshire, United States
Cleveland Clinic Lou Ruvo Center for Brain Health
🇺🇸Las Vegas, Nevada, United States
Mount Sinai School of Medicine
🇺🇸New York, New York, United States
Ohio State University Medical Center
🇺🇸Dublin, Ohio, United States
Penn Memory Center
🇺🇸Philadelphia, Pennsylvania, United States
The Methodist Hospital Research Institute
🇺🇸Houston, Texas, United States
University of Utah Health Sciences Center
🇺🇸Salt Lake City, Utah, United States
Clinical Neuroscience Research Association, Inc
🇺🇸Bennington, Vermont, United States
A.Z. Klina
🇧🇪Brasschaat, Belgium
AZ Sint-Jan Brugge
🇧🇪Brugge, Belgium
Centre Neurologique & de Réadaptation Fonctionnelle
🇧🇪Fraiture, Belgium
Universitair Ziekenhuis Brussel
🇧🇪Bruxelles, Belgium
AZ Groeninge - Campus Kennedylaan
🇧🇪Kortrijk, Belgium
UZ Leuven
🇧🇪Leuven, Belgium
Health Research.
🇨🇦Kamloops, British Columbia, Canada
Health Research
🇨🇦West Vancouver, British Columbia, Canada
True North Clinical Research - Halifax Inc.
🇨🇦Halifax, Nova Scotia, Canada
St. Joseph's HC- Parkwood Institute
🇨🇦London, Ontario, Canada
JBN Medical Diagnostic Services Inc.
🇨🇦Burlington, Ontario, Canada
True North Clinical Research Kentville, Inc
🇨🇦Kentville, Nova Scotia, Canada
Bruyere Continuing Care
🇨🇦Ottawa, Ontario, Canada
DIEX Recherche Sherbrooke Inc.
🇨🇦Sherbrooke, Quebec, Canada
Terveystalo Kamppi
🇫🇮Helsinki, Finland
Douglas Hospital Research Centre
🇨🇦Verdun, Quebec, Canada
Itä-Suomen yliopisto, Aivotutkimusyksikkö
🇫🇮Kuopio, Finland
CRST, Clinical Research Services Turku
🇫🇮Turku, Finland
CHU de Toulouse - Hôpital Purpan
🇫🇷Toulouse cedex 9, Haute Garonne, France
Hopital Roger Salengro - CHU Lille
🇫🇷Lille Cedex, Nord, France
Hôpital Gui de Chauliac
🇫🇷Montpellier, Herault, France
CHU Nantes - Hopital Nord Laënnec
🇫🇷Nantes cedex 1, Loire Atlantique, France
Hôpital des Charpennes
🇫🇷Villeurbanne, Rhone, France
Hôpital Fernand Widal
🇫🇷Paris, France
Klinik Hohe Warte Bayreuth
🇩🇪Bayreuth, Bayern, Germany
Institut fuer Schlaganfall- und Demenzforschung (ISD)
🇩🇪Muenchen, Bayern, Germany
Universitaetsklinikum Ulm
🇩🇪Ulm, Baden Wuerttemberg, Germany
Neuro Centrum Odenwald
🇩🇪Erbach, Hessen, Germany
Universitaetsklinikum Duesseldorf AoeR
🇩🇪Duesseldorf, Nordrhein Westfalen, Germany
Universitaetsklinikum Muenster
🇩🇪Muenster, Nordrhein Westfalen, Germany
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
🇩🇪Mainz, Rheinland Pfalz, Germany
Kopfzentrum Leipzig
🇩🇪Leipzig, Sachsen, Germany
Klinikum Altenburger Land GmbH
🇩🇪Altenburg, Thueringen, Germany
emovis GmbH
🇩🇪Berlin, Germany
Ospedale degli Infermi
🇮🇹Ponderano, Biella, Italy
Neurologie im Tempelhofer Hafen
🇩🇪Berlin, Germany
ASST di Monza
🇮🇹Monza, Milano, Italy
Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone
🇮🇹Palermo, Italy
Fondazione IRCCS Istituto Neurologico Carlo Besta
🇮🇹Milano, Italy
Fondazione Santa Lucia IRCCS
🇮🇹Roma, Italy
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdansk, Poland
Alzheimer Research Center
🇳🇱Amsterdam, Netherlands
Erasmus Medisch Centrum
🇳🇱Rotterdam, Netherlands
Research site
🇯🇵Himeji-shi, Hyogo-Ken, Japan
Umberto I Pol. di Roma-Università di Roma La Sapienza
🇮🇹Roma, Italy
PALLMED Sp. z o.o.
🇵🇱Bydgoszcz, Poland
SPZOZ Centralny Szpital Kliniczny UM w Lodzi
🇵🇱Lodz, Poland
Centrum Diagnostyczno - Terapeutyczne "MEDICUS" Sp.z o.o.
🇵🇱Lubin, Poland
NZOZ "NEURO-KARD", "Ilkowski i Partnerzy" Sp. Partn. Lek.
🇵🇱Poznan, Poland
Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie
🇵🇱Lublin, Poland
Osrodek Badan Klinicznych EUROMEDIS
🇵🇱Szczecin, Poland
mMED Maciej Czarnecki
🇵🇱Warszawa, Poland
ALTHAIA Hospital Sant Joan de Deu
🇪🇸Manresa, Barcelona, Spain
Hospital Universitario Reina Sofía
🇪🇸Cordoba, Córdoba, Spain
Hospital Universitari Quiron Dexeus
🇪🇸Barcelona, Spain
Skånes Universitetssjukhus, Malmö
🇸🇪Malmö, Sweden
Hospital Universitari de Bellvitge
🇪🇸Barcelona, Spain
Sahlgrenska Universitetssjukhuset, Mölndal Sjukhus
🇸🇪Mölndal, Sweden
Hospital Universitari Arnau de Vilanova
🇪🇸Lleida, Spain
Akademiska Sjukhuset
🇸🇪Uppsala, Sweden
Medizinisches Zentrum MZB Biel
🇨🇭Biel/Bienne, Switzerland
Universitären Psychiatrischen Kliniken Basel (UPK)
🇨🇭Basel, Switzerland
Karolinska Universitetssjukhuset, Huddinge
🇸🇪Stockholm, Sweden
Hôpitaux Universitaires de Genève - HUG
🇨🇭Geneve 14, Switzerland
Centre Hospitalier Universitaire Vaudois
🇨🇭Lausanne, Switzerland
Institut fuer Regenerative Medizin (IREM) der Universitaet Zuerich, Zentrum fuer Praevention und Demenztherapie
🇨🇭Schlieren, Switzerland
Ospedale Civico
🇨🇭Lugano, Switzerland
Infinity Clinical Research, LLC
🇺🇸Hollywood, Florida, United States
Hospital del Mar
🇪🇸Barcelona, Spain
Recherches Neuro-Hippocampe Inc.
🇨🇦Gatineau, Quebec, Canada
Institute for Memory Impairments
🇺🇸Irvine, California, United States
Pacific Neuroscience Medical Group
🇺🇸Oxnard, California, United States
Associated Neurologists of Southern Connecticut, PC
🇺🇸Fairfield, Connecticut, United States
Quantum Laboratories Inc.
🇺🇸Deerfield Beach, Florida, United States
Meridien Research
🇺🇸Brooksville, Florida, United States
Weill Cornell Medical College-New York Presbyterian Hospital
🇺🇸New York, New York, United States
Northwest Neurological, PLLC
🇺🇸Spokane, Washington, United States
Universitair Ziekenhuis Gent
🇧🇪Gent, Belgium
AZ Delta
🇧🇪Roeselare, Belgium
Kawartha Regional Memory Clinic
🇨🇦Peterborough, Ontario, Canada
Recherche Sepmus, Inc.
🇨🇦Greenfield Park, Quebec, Canada
Centre de Recherche Clinique du Gérontopôle - Cité de la Santé
🇫🇷Toulouse, Haute Garonne, France
CHU Rennes - Hopital Pontchaillou
🇫🇷Rennes cedex 09, Ille Et Vilaine, France
Bezirkskrankenhaus Guenzburg
🇩🇪Gunzburg, Baden Wuerttemberg, Germany
ISPG - Institut fuer Studien zur Psychischen Gesundheit
🇩🇪Mannheim, Baden Wuerttemberg, Germany
Nervenfachaerztlichen Gemeinschaftspraxis Ulm
🇩🇪Ulm, Baden Wuerttemberg, Germany
Klinikum rechts der Isar der TU Muenchen
🇩🇪Muenchen, Bayern, Germany
Neuropraxis Muenchen Sued
🇩🇪Unterhaching, Bayern, Germany
Klinikum Chemnitz gGmbH
🇩🇪Chemnitz, Sachsen, Germany
Azienda Ospedaliera Card. G. Panico
🇮🇹Tricase, Lecce, Italy
Azienda Ospedaliera di Perugia Ospedale S. Maria della Misericordia
🇮🇹Perugia, Italy
Research Site
🇯🇵Shizuoka-shi, Shizuoka-Ken, Japan
Neuro-Care Gabriela Klodowska
🇵🇱Slaskie, Poland
NZOZ "SENIOR" Poradnia Psychogeriatryczna
🇵🇱Sopot, Poland
Clinica Universidad de Navarra
🇪🇸Pamplona, Navarra, Spain
Hospital General Universitario de Elche
🇪🇸Elche, Alicante, Spain
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Spain
Senior Adult Specialty Research
🇺🇸Austin, Texas, United States
Wake Forest Baptist Health
🇺🇸Winston-Salem, North Carolina, United States
University Of Colorado Denver
🇺🇸Aurora, Colorado, United States
Yale University School Of Medicine
🇺🇸New Haven, Connecticut, United States
PMG Research of Winston-Salem, LLC
🇺🇸Winston-Salem, North Carolina, United States
Clinical Neuroscience Solutions, Inc.
🇺🇸Orlando, Florida, United States
Axiom Clinical Research of Florida
🇺🇸Tampa, Florida, United States
Novo-Med Zielinski i wspolnicy Sp. j.
🇵🇱Katowice, Poland
Centrum Medyczne Medyk
🇵🇱Rzeszow, Poland
Neurologiczny NZOZ Centrum Leczenia SM
🇵🇱Plewiska, Poland
Podlaskie Centrum Psychogeriatrii
🇵🇱Bialystok, Poland
Schwerpunktpraxis fuer Neurologie, Psychiatrie und Klinische Studien
🇩🇪Bielefeld, North Rhine-Westphalia, Germany
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States