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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT02477800
Registration number
NCT02477800
Ethics application status
Date submitted
18/06/2015
Date registered
23/06/2015
Date last updated
2/09/2021
Titles & IDs
Public title
221AD301 Phase 3 Study of Aducanumab (BIIB037) in Early Alzheimer's Disease
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Scientific 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
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Secondary ID [1]
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2015-000966-72
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Secondary ID [2]
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221AD301
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Universal Trial Number (UTN)
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Trial acronym
ENGAGE
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Alzheimer's Disease
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Condition category
Condition code
Neurological
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Alzheimer's disease
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Neurological
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0
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0
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Dementias
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Aducanumab (BIIB037)
Treatment: Drugs - Aducanumab (BIIB037)
Treatment: Drugs - Placebo
Experimental: Low Dose - Monthly intravenous (IV) infusion
Experimental: High Dose - Monthly intravenous (IV) infusion
Treatment: Drugs: Aducanumab (BIIB037)
Low dose
Treatment: Drugs: Aducanumab (BIIB037)
High dose
Treatment: Drugs: Placebo
Placebo
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SB) Score at Week 78
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Assessment method [1]
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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.
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Timepoint [1]
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Baseline, Week 78
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Secondary outcome [1]
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Change From Baseline in Mini-Mental State Examination (MMSE) Score at Week 78
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Assessment method [1]
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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.
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Timepoint [1]
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Baseline, Week 78
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Secondary outcome [2]
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Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (13 Items) (ADAS-Cog 13) Score at Week 78
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Assessment method [2]
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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.
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Timepoint [2]
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Baseline, Week 78
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Secondary outcome [3]
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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
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Assessment method [3]
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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.
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Timepoint [3]
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Baseline, Week 78
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Eligibility
Key inclusion criteria
Key
- 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
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Minimum age
50
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Maximum age
85
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Sex
Both males and females
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Can healthy volunteers participate?
No
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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
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 3
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Statistical methods / analysis
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Recruitment
Recruitment status
Terminated
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
13/08/2015
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
8/08/2019
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Sample size
Target
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Accrual to date
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Final
1653
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Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
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Recruitment hospital [1]
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St Vincent's Hospital Sydney - Darlinghurst
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Central Coast Neurosciences Research, Gosford - East Gosford
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Central Coast Neurosciences Research - Erina
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KARA Institute for Neurological Diseases - North Ryde
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Calvary Mater Newcastle - Waratah
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The Prince Charles Hospital - Chermside
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Royal Brisbane and Women's Hospital - Herston
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Austin Hospital - Heidelberg
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Royal Melbourne Hospital - Parkville
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Neurodegenerative Disorders Research - West Perth
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2010 - Darlinghurst
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2250 - East Gosford
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2250 - Erina
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2113 - North Ryde
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2298 - Waratah
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4032 - Chermside
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4006 - Herston
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4350 - Toowoomba
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3128 - Box Hill
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3084 - Heidelberg
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3050 - Parkville
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6005 - West Perth
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Biogen
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Ethics approval
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Summary
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].
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Trial website
https://clinicaltrials.gov/ct2/show/NCT02477800
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
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Medical Director
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Biogen
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT02477800
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