A Study to Verify the Clinical Benefit of Aducanumab in Participants With Early Alzheimer's Disease

Alzheimer's Disease Clinical Trial

— ENVISION  

Official title:

A Phase 3b/4 Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Verify the Clinical Benefit of Aducanumab (BIIB037) in Participants With Alzheimer's Disease

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05310071
• Other study ID #: 221AD305
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 2, 2022
• Est. completion date: October 31, 2026

Study information

• Verified date: February 2024
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to verify the clinical benefit of monthly doses of aducanumab in slowing cognitive and functional impairment as measured by changes in the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) score as compared with placebo in participants with early Alzheimer's disease.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1512
• Est. completion date: October 31, 2026
• Est. primary completion date: December 27, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years to 85 Years

Eligibility

Key Inclusion Criteria:

• The participant must have confirmed amyloid beta pathology by cerebrospinal fluid (CSF) or amyloid PET

• Must have a history of subjective memory decline with gradual onset and slow progression over the 6 months before Screening, confirmed by study partner

• The participant must have 1 informant/care partner who, in the Investigator's opinion, has frequent and sufficient contact with the participant (at least 10 hours/week in person or by phone) as to be able to provide accurate information about the participant's cognitive and functional abilities over time

• Must meet all of the following clinical criteria for MCI due to Alzheimer's disease or mild Alzheimer's disease according to National Institute on Aging and Alzheimer's Association (NIA-AA) criteria

1. Have an MMSE score between 22 and 30 inclusive

2. Have a CDR memory score >0.5

3. Have a Clinical Dementia Rating Scale Global Score (CDR-GS) of 0.5 or 1.0

4. Have a Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) score of 85 or lower indicative of objective cognitive impairment

• Apart from a clinical diagnosis of early Alzheimer's disease, the participant must be in good health as determined by the Investigator based on medical history and screening assessments

• Must consent to apolipoprotein E (ApoE) genotyping. (Note: Participants are not required to be ApoE e4 carriers)

Key Exclusion Criteria:

• Any uncontrolled medical or neurological/neurodegenerative condition (other than Alzheimer's disease) that, in the opinion of the Investigator, might be a contributing cause of the participant's cognitive impairment

• Clinically significant and/or unstable psychiatric illness within 6 months prior to Screening

• Transient ischemic attack or stroke or any unexplained loss of consciousness within 1 year prior to Screening

• History of severe allergic or anaphylactic reactions or of hypersensitivity to any of the inactive ingredients in the drug product

• Participation in any study with purported disease-modifying effect in Alzheimer's disease within 12 months prior to Screening unless documentation of receipt of placebo is available

• Current use or previous use of medications with a purported disease-modifying effect in Alzheimer's disease, outside of investigational studies

• Use of any medications that, in the opinion of the Investigator, may contribute to cognitive impairment, put the participant at higher risk for AEs, or impair the participant's ability to perform cognitive testing or complete study procedures

• Use of any investigational drug

• Prior exposure to aducanumab either commercially or by participation in a previous study with aducanumab. (Participants are eligible if they did not receive active aducanumab.)

• A negative PET scan result with any amyloid-targeting ligand within 12 months prior to Screening

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

Drug:
• Aducanumab
Administered as specified in the treatment arm.
• Placebo
Administered as specified in the treatment arm.

Locations

Country	Name	City	State
Australia	Box Hill Hospital	Box Hill	Victoria
Australia	St Vincent's Hospital Sydney	Darlinghurst	New South Wales
Australia	Austin Health	Heidelberg	Victoria
Australia	KaRa Institute of Neurological Diseases	Macquarie Park	New South Wales
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	Australian Alzheimer's Research Foundation	Nedlands	Western Australia
Australia	Royal Melbourne Hospital	Parkville	Victoria
Belgium	Universitair Ziekenhuis Brussel	Brussel
Belgium	AZ Groeninge	Kortrijk
Belgium	UZ Leuven	Leuven	Flemish Brabant
Brazil	Instituto de Neurologia de Curitiba - Hospital Ecoville	Curitiba	Paraná
Brazil	Trial Tech Tecnologia em Pesquisas com Medicamentos Ltda	Curitiba	Paraná
Brazil	Instituto do Cerebro do Rio Grande do Sul	Porto Alegre	Rio Grande Do Sul
Brazil	IPq-HCFMUSP - Instituto de Psiquiatria do Hospital das Clínicas da FMUSP	São Paulo	Sao Paulo
Canada	University of Calgary - Heritage Medical Research Clinic	Calgary	Alberta
Canada	Clinique de la Memoire de l'Outaouais	Gatineau	Quebec
Canada	MoCA Research and Innovation Inc	Greenfield-Park	Quebec
Canada	Centricity Research Halifax	Halifax	Nova Scotia
Canada	Recherches Neuro-Hippocampe Inc., d/b/a Ottawa Memory Clinic	Ottawa	Ontario
Canada	Kawartha Centre - Redefining Healthy Aging	Peterborough	Ontario
Canada	Baycrest Centre for Geriatric Care	Toronto	Ontario
Canada	Centricity Research Toronto LMC	Toronto	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	Toronto Memory Program (Neurology Research Inc.)	Toronto	Ontario
Canada	Toronto Western Hospital	Toronto	Ontario
Canada	UBC Hospital	Vancouver	British Columbia
Finland	Terveystalo Ruoholahti	Helsinki
Finland	CRST, Clinical Research Services Turku	Turku
France	Groupe Hospitalier Pellegrin - Hôpital Pellegrin	Bordeaux Cedex	Gironde
France	Hopital Roger Salengro - CHU Lille	Lille Cedex	Nord
France	Hôpital de la Timone	Marseille cedex 05	Bouches-du-Rhône
France	Hopital Gui de Chauliac	Montpellier	Herault
France	Groupe Hospitalier Pitie-Salpetriere	Paris
France	Hôpital Broca	Paris
France	Hôpital Lariboisière	Paris cedex 10	Paris
France	CHU Rennes - Pontchaillou	Rennes cedex 9	Ille Et Vilaine
France	CHU Nantes - Hopital Nord Laënnec	Saint-Herblain	Loire Atlantique
France	CHU Strasbourg - Hôpital Hautepierre	Strasbourg Cedex	Bas Rhin
France	Hôpital La Grave	Toulouse Cedex 9	Haute Garonne
France	Hôpital des Chapennes	Villeurbanne	Rhone
Germany	Zentrum für klinische Forschung Dr.med. Irma Schöll	Bad Homburg	Hessen
Germany	Klinikum Bayreuth GmbH- Hohe Warte	Bayreuth	Bayern
Germany	Charité - Universitätsmedizin Berlin	Berlin
Germany	NEUROZENTRUM tempelhof.berlin	Berlin
Germany	Katholisches Klinikum Bochum gGmbH	Bochum	Nordrhein Westfalen
Germany	Deutsches Zentrum fuer Neurodegenerative Erkrankungen (DZNE)	Bonn	Nordrhein Westfalen
Germany	Universitaetsklinikum Frankfurt Goethe-Universitaet	Frankfurt	Hessen
Germany	Universitaetsmedizin Goettingen	Goettingen	Niedersachsen
Germany	Universitaetsklinikum Koeln	Koeln	Nordrhein Westfalen
Germany	Universitaetsklinikum Magdeburg	Magdeburg	Sachsen Anhalt
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 Tuebingen	Tuebingen	Baden Wuerttemberg
Italy	Ospedale di Arzignano	Arzignano VI	Vicenza
Italy	Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili)	Brescia
Italy	Fondazione Istituto G.Giglio di Cefalù	Cefalù	Palermo
Italy	IRCCS Ospedale Policlinico San Martino	Genova
Italy	Ospedale San Raffaele	Milano
Italy	ASST di Monza	Monza	Milano
Italy	Azienda Ospedaliera Universitaria- Università degli Studi della Campania "Luigi Vanvitelli"	Napoli
Italy	Azienda Ospedaliera e Universitaria di Perugia	Perugia
Italy	Azienda Ospedaliera Universitaria Policlinico Umberto I - Università di Roma La Sapienza	Roma
Italy	Fondazione Santa Lucia IRCCS	Roma
Italy	Azienda Ospedaliera Universitaria OO. RR. S. Giovanni di Dio e Ruggi D'Aragona	Salerno
Italy	Azienda Ospedaliera Card. G. Panico	Tricase	Lecce
Japan	Tokushukai Shonan Atsugi Hospital	Atsugi-shi	Kanagawa-Ken
Japan	Memory Clinic Ochanomizu	Bunkyo-ku	Tokyo-To
Japan	Hakuyokai Kashiwado Hospital	Chiba-shi	Chiba-Ken
Japan	Inage Neurology and Memory Clinic	Chiba-shi	Chiba-Ken
Japan	Himeji Central Hospital Clinic	Himeji-shi	Hyogo-Ken
Japan	Tokushukai Shonan Kamakura General Hospital	Kamakura-shi	Kanagawa-Ken
Japan	Midorikai Takesato Hospital	Kasukabe-shi	Saitama-Ken
Japan	Teikyo University Hospital, Mizonokuchi	Kawasaki-shi	Kanagawa-Ken
Japan	Tokushukai Kishiwada Tokushukai Hospital	Kishiwada-shi	Osaka-Fu
Japan	Kagawa University Hospital	Kita-gun	Kagawa-Ken
Japan	National Center of Neurology and Psychiatry	Kodaira-shi	Tokyo-To
Japan	Southern Tohoku Medical Clinic	Koriyama-shi	Fukushima-Ken
Japan	Katayama Medical Clinic	Kurashiki-shi	Okayama-Ken
Japan	NHO Utano National Hospital	Kyoto-shi	Kyoto-Fu
Japan	Rakuwakai Otowa Rehabilitation Hospital	Kyoto-shi	Kyoto-Fu
Japan	National Center For Geriatrics And Gerontology	Obu-shi	Aichi-Ken
Japan	NHO Hiroshima-Nishi Medical Center	Otake-shi	Hiroshima-Ken
Japan	Osaka University Hospital	Suita-shi	Osaka-Fu
Japan	Tokushukai Yamagata Tokushukai Hospital	Yamagata-shi	Yamagata-Ken
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam	Gyeonggi-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Konkuk University Medical Center	Seoul
Mexico	Health Pharma Professional Research S.A. de C.V.	Ciudad de México	Distrito Federal
Mexico	Hospital Mexico Americano SC	Guadalara	Jalisco
Mexico	AVIX Investigación Clínica S.C	Monterrey	Nuevo León
Mexico	Centro de Estudios Clinicos y Especialidades Medicas, S.C.	Monterrey	Nuevo León
Poland	Podlaskie Centrum Psychogeriatrii	Bialystok	Podkarpackie Wojewódctwo
Poland	PROMENTE Sp. z o.o.	Bydgoszcz	Kujawsko-Pomorskie Województwo
Poland	Nzoz Novo-Med	Katowice	Slaskie Województwo
Poland	Neuro-Care Gabriela Klodowska	Siemianowice Slaskie	Slaskie Województwo
Poland	Centrum Medyczne Senior	Sopot	Pomorskie Województwo
Poland	Centrum Medyczne NeuroProtect	Warszawa	Mazowieckie Województwo
Poland	NZOZ Wroclawskie Centrum Alzheimerowskie	Wroclaw
Portugal	Hospital de Braga	Braga
Portugal	Centro Hospitalar e Universitário de Coimbra E.P.E. - Hospitais da Universidade de Coimbra	Coimbra	Centro
Portugal	CNS-Campus Neurologico Senior	Torres Vedras	Oeste
Spain	Fundacio ACE	Barcelona
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitario Reina Sofia	Cordoba	Córdoba
Spain	Hospital Universitari de Santa Maria	Lleida
Spain	Clinica Universidad de Navarra (MAD)	Madrid
Spain	Clinica Universidad de Navarra	Pamplona	Navarra
Spain	Policlinica Gipuzkoa	San Sebastian	Guipuzcoa
Spain	Hospital Victoria Eugenia	Sevilla
Spain	Hospital Universitari i Politecnic La Fe	Valencia
Spain	Hospital Universitario Dr. Peset	Valencia
Sweden	Skane University Hospital	Malmö	Scania
Sweden	Sahlgrenska Universitetssjukhuset, Mölndal Sjukhus	Mölndal	Västra Götaland
Sweden	Karolinska Universitetssjukhuset	Stockholm
United Kingdom	Re Cognition Health Bristol	Bristol
United Kingdom	Brain Health Scotland Life Sciences	Edinburgh	Lothian Region
United Kingdom	Charing Cross Hospital	London	Greater London
United Kingdom	Institute of Psychiatry, Psychology and Neuroscience	London	Greater London
United Kingdom	Re:Cognition Health Ltd (London)	London	Greater London
United Kingdom	Glasgow Memory Clinic Ltd	Motherwell	Strathclyde
United Kingdom	Moorgreen Hospital	Southampton	Hampshire
United Kingdom	Southampton General Hospital	Southampton	Hampshire
United States	Abington Neurological Associates, LTD	Abington	Pennsylvania
United States	Neurological Associates of Albany, PC	Albany	New York
United States	Dent Neurologic Institute	Amherst	New York
United States	JEM Research Institute	Atlantis	Florida
United States	University of Colorado Anschutz Medical Campus	Aurora	Colorado
United States	Senior Adult Specialty Research	Austin	Texas
United States	Mountain Neurological Research Center	Basalt	Colorado
United States	McLean Hospital	Belmont	Massachusetts
United States	The Memory Clinic	Bennington	Vermont
United States	ECommunity Research, LLC	Boca Raton	Florida
United States	Brigham and Women's Hospital Department of Neurology	Boston	Massachusetts
United States	University of Virginia Health System	Charlottesville	Virginia
United States	Ohio State University Medical Center	Columbus	Ohio
United States	Neurology Clinic, PC	Cordova	Tennessee
United States	Kerwin Medical Center	Dallas	Texas
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Brain Matters Research	Delray Beach	Florida
United States	Rhode Island Hospital	East Providence	Rhode Island
United States	Rhode Island Mood & Memory Research Institute	East Providence	Rhode Island
United States	Alexian Brothers Medical Center - Neuroscience Research Institute	Elk Grove Village	Illinois
United States	Yale University	Fairfield	Connecticut
United States	University of Kansas Medical Center Research Institute, Inc.	Fairway	Kansas
United States	Michigan Institute for Neurological Disorders	Farmington Hills	Michigan
United States	Health Initiatives Research	Fayetteville	Arkansas
United States	Neuropsychiatric Research Center of Southwest Florida	Fort Myers	Florida
United States	Neuropain Medical Center	Fresno	California
United States	Hattiesburg Clinic, PA	Hattiesburg	Mississippi
United States	Infinity Clinical Research, LLC	Hollywood	Florida
United States	Hawaii Pacific Neuroscience	Honolulu	Hawaii
United States	Baylor College Of Medicine	Houston	Texas
United States	The Methodist Hospital Research Institute	Houston	Texas
United States	Indiana University School of Medicine	Indianapolis	Indiana
United States	Irvine Center for Clinical Research, Inc.	Irvine	California
United States	Genesis Neuroscience Clinic	Knoxville	Tennessee
United States	Charter Research, LLC	Lady Lake	Florida
United States	Cleveland Clinic Lou Ruvo Center for Brain Health	Las Vegas	Nevada
United States	Las Vegas Medical Research	Las Vegas	Nevada
United States	Mary S. Easton Center for Alzheimer's Disease Research, UCLA	Los Angeles	California
United States	AMC Research, LLC	Matthews	North Carolina
United States	Medical College of Wisconsin, Inc.	Milwaukee	Wisconsin
United States	Institute for Neurodegenerative Disorders (IND)	New Haven	Connecticut
United States	Yale University School Of Medicine	New Haven	Connecticut
United States	Mount Sinai	New York	New York
United States	New York University Medical Center PRIME	New York	New York
United States	Hoag Memorial Hospital Presbyterian	Newport Beach	California
United States	Boston Center for Memory	Newton	Massachusetts
United States	Glennan Center for Geriatrics and Gerontology	Norfolk	Virginia
United States	Research Center for Clinical Studies, Inc.	Norwalk	Connecticut
United States	Renstar Medical Research	Ocala	Florida
United States	K2 Medical Research, LLC	Ocoee	Florida
United States	Lynn Health Science Institute	Oklahoma City	Oklahoma
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Headlands Research LLC	Orlando	Florida
United States	K2 Medical Research	Orlando	Florida
United States	K2 Medical Research, LLC	Orlando	Florida
United States	Sharlin Health and Neurology	Ozark	Missouri
United States	South Shore Neurologic Associates, P.C.	Patchogue	New York
United States	Banner Alzheimer's Institute	Phoenix	Arizona
United States	Barrow Neurological Institute	Phoenix	Arizona
United States	Xenoscience Inc.	Phoenix	Arizona
United States	Donald S. Marks, M.D., P.C.	Plymouth	Massachusetts
United States	Quantum Laboratories Inc.	Pompano Beach	Florida
United States	Coastal Neurology PA	Port Royal	South Carolina
United States	ActivMed Practices and Research	Portsmouth	New Hampshire
United States	Butler Hospital	Providence	Rhode Island
United States	Anderson Clinical Research	Redlands	California
United States	National Clinical Research Inc. - Richmond	Richmond	Virginia
United States	University of Rochester - PARENT	Rochester	New York
United States	Center for Memory and Aging	Saint Paul	Minnesota
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Sutter Health-San Francisco	San Francisco	California
United States	University of California San Francisco (PARENT)	San Francisco	California
United States	The Neuron Clinic	San Marcos	California
United States	Syrentis Clinical Research	Santa Ana	California
United States	HonorHealth Neurology	Scottsdale	Arizona
United States	Mayo Clinic Arizona	Scottsdale	Arizona
United States	University of Washington Medical Center	Seattle	Washington
United States	California Neuroscience Research, LLC	Sherman Oaks	California
United States	Kingfisher Cooperative, LLC	Spokane	Washington
United States	Brain Matters Research	Stuart	Florida
United States	Banner Sun Health Research Institute	Sun City	Arizona
United States	USF Health Byrd Institute	Tampa	Florida
United States	CenExel Advanced Memory Research Institute of NJ	Toms River	New Jersey
United States	Banner Alzheimer's Institute	Tucson	Arizona
United States	Central States Research, LLC	Tulsa	Oklahoma
United States	Howard University Health Sciences	Washington	District of Columbia
United States	Ascension Via Christi Research, a division of Ascension Via Christi Hospitals Wichita, Inc.	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Brazil,  Canada,  Finland,  France,  Germany,  Italy,  Japan,  Korea, Republic of,  Mexico,  Poland,  Portugal,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in CDR-SB Score at Week 78	The CDR 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 participant examination, the rater assigns a score describing the participant's current performance level in each of these domains of life functioning. The "Sum of boxes" scoring methodology (CDR-SB) sums the score for each of the 6 domains and provides a value ranging from 0 to 18 with higher scores indicating greater impairment. Positive change from baseline indicates greater impairment.	Baseline, Week 78
Secondary	Change From Baseline in Integrated Alzheimer's Disease Rating Scale (iADRS) Score at Weeks 78 and 106	The iADRS composite captures decline in both cognition and daily function. The iADRS is a simple linear combination of Alzheimer's disease assessment scale, cognitive subscale (ADAS-Cog13) and the Alzheimer's disease cooperative study scale for activities of daily living in mild cognitive impairment (ADCS-ADL-MCI). The iADRS scale ranges from 0-138, higher scores indicating better performance.	Baseline, Weeks 78 and 106
Secondary	Change From Baseline in ADCS-ADL-MCI Score at Weeks 78 and 106	The ADCS-ADL-MCI is a functional evaluation scale for MCI participants, based on information provided by an informant who rates 18 areas of daily living, with total score ranging from 0-53. Higher scores indicate greater independent, healthy functioning. Positive change from baseline indicates healthy functioning.	Baseline, Weeks 78 and 106
Secondary	Change From Baseline in ADAS-Cog13 Score at Weeks 78 and 106	The ADCS-ADAS-Cog13 is a brief objective cognitive assessment of the severity of cognitive symptoms of Alzheimer's disease. The ADAS-Cog13 score ranges from 0 to 85, with higher scores indicating worse performance.	Baseline, Weeks 78 and 106
Secondary	Change From Baseline in Mini-Mental State Examination (MMSE) Score at Weeks 78 and 106	The MMSE is a brief cognitive screening tool that provides clinicians the ability to rapidly assess cognitive ability in less than 10 minutes. The MMSE score ranges from 0-30, with higher scores indicating better performance.	Baseline, Weeks 78 and 106
Secondary	Change From Baseline in Neuropsychiatric Inventory-10 (NPI-10) Score at Weeks 78 and 106	The NPI-10 is a questionnaire administered to the informant, designed to obtain information on the presence of neuropsychiatric symptoms and behaviors in a participant with Alzheimer's disease. Ten areas are assessed: delusions, hallucinations, agitation/aggression, depression, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability and aberrant motor behavior. The NPI total score ranges from 0 to 120. Higher scores indicates greater impairment.	Baseline, Weeks 78 and 106
Secondary	Change From Baseline in Amyloid Positron Emission Tomography (PET) Signal at Weeks 78 and 104	The cerebral amyloid plaque level was measured by amyloid PET imaging.	Baseline, Weeks 78 and 104
Secondary	Change From Baseline in Tau PET Signal at Weeks 78 and 104	The cerebral tau level was measured by tau PET imaging.	Baseline, Weeks 78 and 104
Secondary	Change From Baseline in CDR-SB Score at Week 106	The CDR 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 participant examination, the rater assigns a score describing the participant's current performance level in each of these domains of life functioning. The "Sum of boxes" scoring methodology (CDR-SB) sums the score for each of the 6 domains and provides a value ranging from 0 to 18 with higher scores indicating greater impairment. Positive change from baseline indicates greater impairment.	Baseline, Week 106
Secondary	Change From Baseline in Global Statistical Test (GST) Composite Z-Score	The GST is a composite z-score defined as the average of standardized z-scores of the CDR-SB, ADASCog13, and ADCS-ADL-MCI. A positive change from baseline indicates improvement.	Baseline, Weeks 78 and 106