221AD302 Phase 3 Study of Aducanumab (BIIB037) in Early Alzheimer's Disease

Alzheimer's Disease Clinical Trial

— EMERGE  

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: NCT02484547
• Other study ID #: 221AD302
• Secondary ID: 2015-000967-15
• Status: Terminated
• Phase: Phase 3
• Start date: September 15, 2015
• Est. completion date: August 5, 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: 1643
• Est. completion date: August 5, 2019
• Est. primary completion date: August 5, 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
Belgium	A.Z. Klina	Brasschaat
Belgium	AZ Sint-Jan Brugge	Brugge
Belgium	Universitair Ziekenhuis Brussel	Bruxelles
Belgium	Centre Neurologique & de Réadaptation Fonctionnelle	Fraiture
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	AZ Groeninge - Campus Kennedylaan	Kortrijk
Belgium	UZ Leuven	Leuven
Belgium	AZ Delta	Roeselare
Canada	JBN Medical Diagnostic Services Inc.	Burlington	Ontario
Canada	Recherches Neuro-Hippocampe Inc.	Gatineau	Quebec
Canada	Recherche Sepmus, Inc.	Greenfield Park	Quebec
Canada	True North Clinical Research - Halifax Inc.	Halifax	Nova Scotia
Canada	Health Research.	Kamloops	British Columbia
Canada	True North Clinical Research Kentville, Inc	Kentville	Nova Scotia
Canada	St. Joseph's HC- Parkwood Institute	London	Ontario
Canada	Bruyere Continuing Care	Ottawa	Ontario
Canada	Kawartha Regional Memory Clinic	Peterborough	Ontario
Canada	DIEX Recherche Sherbrooke Inc.	Sherbrooke	Quebec
Canada	Toronto Western Hospital	Toronto	Ontario
Canada	Douglas Hospital Research Centre	Verdun	Quebec
Canada	Health Research	West Vancouver	British Columbia
Finland	Terveystalo Kamppi	Helsinki
Finland	Itä-Suomen yliopisto, Aivotutkimusyksikkö	Kuopio
Finland	CRST, Clinical Research Services Turku	Turku
France	Hopital Roger Salengro - CHU Lille	Lille Cedex	Nord
France	Hôpital de la Timone	Marseille	Bouches-du-Rhône
France	Hôpital Gui de Chauliac	Montpellier	Herault
France	CHU Nantes - Hopital Nord Laënnec	Nantes cedex 1	Loire Atlantique
France	Hôpital Fernand Widal	Paris
France	CHU Rennes - Hopital Pontchaillou	Rennes cedex 09	Ille Et Vilaine
France	Centre de Recherche Clinique du Gérontopôle - Cité de la Santé	Toulouse	Haute Garonne
France	CHU de Toulouse - Hôpital Purpan	Toulouse cedex 9	Haute Garonne
France	Hôpital des Charpennes	Villeurbanne	Rhone
Germany	Klinikum Altenburger Land GmbH	Altenburg	Thueringen
Germany	Klinik Hohe Warte Bayreuth	Bayreuth	Bayern
Germany	emovis GmbH	Berlin
Germany	Neurologie im Tempelhofer Hafen	Berlin
Germany	Schwerpunktpraxis fuer Neurologie, Psychiatrie und Klinische Studien	Bielefeld	North Rhine-Westphalia
Germany	Klinikum Chemnitz gGmbH	Chemnitz	Sachsen
Germany	Universitaetsklinikum Duesseldorf AoeR	Duesseldorf	Nordrhein Westfalen
Germany	Neuro Centrum Odenwald	Erbach	Hessen
Germany	Bezirkskrankenhaus Guenzburg	Gunzburg	Baden Wuerttemberg
Germany	Kopfzentrum Leipzig	Leipzig	Sachsen
Germany	Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz	Mainz	Rheinland Pfalz
Germany	ISPG - Institut fuer Studien zur Psychischen Gesundheit	Mannheim	Baden Wuerttemberg
Germany	Institut fuer Schlaganfall- und Demenzforschung (ISD)	Muenchen	Bayern
Germany	Klinikum rechts der Isar der TU Muenchen	Muenchen	Bayern
Germany	Universitaetsklinikum Muenster	Muenster	Nordrhein Westfalen
Germany	Zentrum f. Neurologisch- Psychiatrische Studien und Begutachtung	Siegen	Nordrhein Westfalen
Germany	Nervenfachaerztlichen Gemeinschaftspraxis Ulm	Ulm	Baden Wuerttemberg
Germany	Universitaetsklinikum Ulm	Ulm	Baden Wuerttemberg
Germany	Neuropraxis Muenchen Sued	Unterhaching	Bayern
Italy	Fondazione IRCCS Istituto Neurologico Carlo Besta	Milano
Italy	ASST di Monza	Monza	Milano
Italy	Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone	Palermo
Italy	Azienda Ospedaliera di Perugia Ospedale S. Maria della Misericordia	Perugia
Italy	Ospedale degli Infermi	Ponderano	Biella
Italy	Fondazione Santa Lucia IRCCS	Roma
Italy	Umberto I Pol. di Roma-Università di Roma La Sapienza	Roma
Italy	Azienda Ospedaliera Card. G. Panico	Tricase	Lecce
Japan	Research Site	Amagasaki-shi	Hyogo-Ken
Japan	Research Site	Fukuoka-shi	Fukuoka-Ken
Japan	Research site	Himeji-shi	Hyogo-Ken
Japan	Research Site	Himeji-shi	Hyogo-Ken
Japan	Research Site	Iwata-shi	Shizuoka-Ken
Japan	Research Site	Kishiwada-shi	Osaka-Fu
Japan	Research Site	Kita-gun	Kagawa-Ken
Japan	Research Site	Kobe-shi	Hyogo-Ken
Japan	Research Site	Kurashiki-shi	Okayama-Ken
Japan	Research Site	Kurume-shi	Fukuoka-Ken
Japan	Research Site	Kyoto-shi	Kyoto-Fu
Japan	Research Site	Kyoto-shi	Kyoto-Fu
Japan	Research Site	Nishisonogi	Nagasaki-Ken
Japan	Research Site	Obu-shi	Aichi-Ken
Japan	Research Site	Okayama-shi	Okayama-Ken
Japan	Research Site	Osaka-shi	Osaka-Fu
Japan	Research Site	Osaka-shi	Osaka-Fu
Japan	Research Site	Osaka-shi	Osaka-Fu
Japan	Research Site	Otake-shi	Hiroshima-Ken
Japan	Research Site	Sennan-shi	Osaka-Fu
Japan	Research Site	Shizuoka-shi	Shizuoka-Ken
Japan	Research Site	Shizuoka-shi	Shizuoka-Ken
Japan	Research Site	Suita-shi	Osaka-Fu
Japan	Research Site	Toon-shi	Ehime-Ken
Japan	Research Site	Tsu-shi	Mie-Ken
Japan	Research Site	Tsukuba-gun	Okayama-Ken
Japan	Research Site	Yufu-shi	Oita-Ken
Netherlands	Alzheimer Research Center	Amsterdam
Netherlands	Erasmus Medisch Centrum	Rotterdam
Poland	Podlaskie Centrum Psychogeriatrii	Bialystok
Poland	PALLMED Sp. z o.o.	Bydgoszcz
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Novo-Med Zielinski i wspolnicy Sp. j.	Katowice
Poland	SPZOZ Centralny Szpital Kliniczny UM w Lodzi	Lodz
Poland	Centrum Diagnostyczno - Terapeutyczne "MEDICUS" Sp.z o.o.	Lubin
Poland	Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie	Lublin
Poland	Neurologiczny NZOZ Centrum Leczenia SM	Plewiska
Poland	NZOZ "NEURO-KARD", "Ilkowski i Partnerzy" Sp. Partn. Lek.	Poznan
Poland	Centrum Medyczne Medyk	Rzeszow
Poland	Neuro-Care Gabriela Klodowska	Slaskie
Poland	NZOZ "SENIOR" Poradnia Psychogeriatryczna	Sopot
Poland	Osrodek Badan Klinicznych EUROMEDIS	Szczecin
Poland	mMED Maciej Czarnecki	Warszawa
Spain	Hospital del Mar	Barcelona
Spain	Hospital Universitari de Bellvitge	Barcelona
Spain	Hospital Universitari Quiron Dexeus	Barcelona
Spain	Hospital Universitario Reina Sofía	Cordoba	Córdoba
Spain	Hospital General Universitario de Elche	Elche	Alicante
Spain	Hospital Universitari Arnau de Vilanova	Lleida
Spain	ALTHAIA Hospital Sant Joan de Deu	Manresa	Barcelona
Spain	Clinica Universidad de Navarra	Pamplona	Navarra
Spain	Hospital Universitario Virgen Macarena	Sevilla
Sweden	Skånes Universitetssjukhus, Malmö	Malmö
Sweden	Sahlgrenska Universitetssjukhuset, Mölndal Sjukhus	Mölndal
Sweden	Karolinska Universitetssjukhuset, Huddinge	Stockholm
Sweden	Akademiska Sjukhuset	Uppsala
Switzerland	Universitären Psychiatrischen Kliniken Basel (UPK)	Basel
Switzerland	Medizinisches Zentrum MZB Biel	Biel/Bienne
Switzerland	Hôpitaux Universitaires de Genève - HUG	Geneve 14
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne
Switzerland	Ospedale Civico	Lugano
Switzerland	Institut fuer Regenerative Medizin (IREM) der Universitaet Zuerich, Zentrum fuer Praevention und Demenztherapie	Schlieren
United States	Lehigh Center for Clinical Research, LLC	Allentown	Pennsylvania
United States	Emory University Cognitive Neurology Clinic & ADRC	Atlanta	Georgia
United States	JEM Research Institute	Atlantis	Florida
United States	University Of Colorado Denver	Aurora	Colorado
United States	Senior Adult Specialty Research	Austin	Texas
United States	McLean Hospital	Belmont	Massachusetts
United States	Clinical Neuroscience Research Association, Inc	Bennington	Vermont
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Bradenton Research Center, Inc.	Bradenton	Florida
United States	Meridien Research	Brooksville	Florida
United States	Medical Research Health and Education Foundation, Inc	Columbus	Georgia
United States	NeuroStudies.net, LLC	Decatur	Georgia
United States	Quantum Laboratories Inc.	Deerfield Beach	Florida
United States	Ohio State University Medical Center	Dublin	Ohio
United States	Associated Neurologists of Southern Connecticut, PC	Fairfield	Connecticut
United States	Hattiesburg Clinic, PA	Hattiesburg	Mississippi
United States	Infinity Clinical Research, LLC	Hollywood	Florida
United States	Clinical Trial Network	Houston	Texas
United States	The Methodist Hospital Research Institute	Houston	Texas
United States	Josephson, Wallack, Munshower Neurology, PC	Indianapolis	Indiana
United States	Institute for Memory Impairments	Irvine	California
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	Cleveland Clinic Lou Ruvo Center for Brain Health	Las Vegas	Nevada
United States	Empire Neurology, PC	Latham	New York
United States	AdvanceMed Research	Lawrenceville	New Jersey
United States	Renewal Behavioral Health	Long Beach	California
United States	USC Keck School of Medicine	Los Angeles	California
United States	Yale University School Of Medicine	New Haven	Connecticut
United States	Mount Sinai School of Medicine	New York	New York
United States	Weill Cornell Medical College-New York Presbyterian Hospital	New York	New York
United States	Hoag Memorial Hospital Presbyterian	Newport Beach	California
United States	Boston Center for Memory	Newton	Massachusetts
United States	Roper St. Francis Healthcare	North Charleston	South Carolina
United States	Research Center for Clinical Studies, Inc.	Norwalk	Connecticut
United States	Renstar Medical Research	Ocala	Florida
United States	Excell Research, Inc.	Oceanside	California
United States	Clinical Neuroscience Solutions, Inc.	Orlando	Florida
United States	Pacific Neuroscience Medical Group	Oxnard	California
United States	Penn Memory Center	Philadelphia	Pennsylvania
United States	Banner Alzheimer's Institute	Phoenix	Arizona
United States	Xenoscience Inc.	Phoenix	Arizona
United States	ActivMed Practices & Research	Portsmouth	New Hampshire
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Anderson Clinical Research	Redlands	California
United States	University of Utah Health Sciences Center	Salt Lake City	Utah
United States	Pacific Research Network	San Diego	California
United States	University of California San Diego Medical Center	San Diego	California
United States	California Pacific Medical Center	San Francisco	California
United States	Syrentis Clinical Research	Santa Ana	California
United States	St Joseph Heritage Healthcare	Santa Rosa	California
United States	University of Washington Medical Center	Seattle	Washington
United States	Northwest Neurological, PLLC	Spokane	Washington
United States	Stanford University Medical Center	Stanford	California
United States	Banner Sun Health Research Institute	Sun City	Arizona
United States	Axiom Clinical Research of Florida	Tampa	Florida
United States	IMMUNOe International Research Centers	Thornton	Colorado
United States	PMG Research of Winston-Salem, LLC	Winston-Salem	North Carolina
United States	Wake Forest Baptist Health	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Finland,  France,  Germany,  Italy,  Japan,  Netherlands,  Poland,  Spain,  Sweden,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Clinical Dementia Rating Scale - 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) 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