History of Changes for Study: NCT05310071

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

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Study Record Versions

Version	Submitted Date	Changes
1	March 25, 2022	None (earliest Version on record)
2	June 2, 2022	Recruitment Status, Study Status, Contacts/Locations and Oversight
3	June 10, 2022	Contacts/Locations and Study Status
4	June 28, 2022	Contacts/Locations and Study Status
5	July 11, 2022	Study Status and Contacts/Locations
6	July 15, 2022	Contacts/Locations and Study Status
7	July 25, 2022	Contacts/Locations and Study Status
8	August 9, 2022	Study Status and Contacts/Locations
9	September 5, 2022	Contacts/Locations and Study Status
10	September 7, 2022	Contacts/Locations and Study Status
11	September 23, 2022	Contacts/Locations and Study Status
12	October 13, 2022	Study Status and Contacts/Locations
13	November 30, 2022	Study Status, Contacts/Locations and Study Design
14	January 19, 2023	Study Status, IPDSharing and Contacts/Locations
15	March 16, 2023	Contacts/Locations and Study Status
16	April 11, 2023	Contacts/Locations and Study Status
17	May 29, 2023	Contacts/Locations and Study Status
18	June 23, 2023	Contacts/Locations and Study Status
19	August 3, 2023	Contacts/Locations and Study Status
20	September 5, 2023	Study Status and Contacts/Locations
21	October 30, 2023	Contacts/Locations and Study Status
22	November 16, 2023	Study Status and Contacts/Locations
23	December 7, 2023	Study Status and Contacts/Locations
24	December 21, 2023	Contacts/Locations and Study Status
25	January 16, 2024	Study Status and Contacts/Locations
26	February 9, 2024	Recruitment Status, Contacts/Locations and Study Status

Comparison Format:

Merged
Side-by-Side

Study Identification


Unique Protocol ID:	221AD305
Brief Title:	A Study to Verify the Clinical Benefit of Aducanumab in Participants With Early Alzheimer's Disease (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
Secondary IDs:

Study Status


Record Verification:	March 2022
Overall Status:	Not yet recruiting
Study Start:	May 27, 2022
Primary Completion:	June 30, 2026 [Anticipated]
Study Completion:	May 4, 2027 [Anticipated]

First Submitted:	March 25, 2022
First Submitted that Met QC Criteria:	March 25, 2022
First Posted:	April 4, 2022 [Actual]

Last Update Submitted that Met QC Criteria:	March 25, 2022
Last Update Posted:	April 4, 2022 [Actual]

Sponsor/Collaborators


Sponsor:	Biogen
Responsible Party:	Sponsor
Collaborators:

Oversight


U.S. FDA-regulated Drug:	Yes
U.S. FDA-regulated Device:	No
Data Monitoring:	Yes

Study Description


Brief 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.
Detailed Description:

Conditions


Conditions:	Alzheimer's Disease
Keywords:

Study Design


Study Type:	Interventional
Primary Purpose:	Treatment
Study Phase:	Phase 4
Interventional Study Model:	Parallel Assignment
Number of Arms:	2
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation:	Randomized
Enrollment:	1512 [Anticipated]

Arms and Interventions

Arms	Assigned Interventions
Experimental: Aducanumab Participants will receive aducanumab, up to 10 milligrams per kilograms (mg/kg), monthly (once every four weeks), administered as intravenous (IV) infusion.	Drug: Aducanumab Administered as specified in the treatment arm. Other Names: BIIB037 Aducanumab-avwa Aduhelm
Placebo Comparator: Placebo Participants will receive placebo, monthly (once every four weeks), administered as IV infusion.	Drug: Placebo Administered as specified in the treatment arm.

Outcome Measures


Primary Outcome Measures:
1.	Change From Baseline in CDR-SB Score at Week 78 [ Time Frame: Baseline, 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.
Secondary Outcome Measures:
1.	Change From Baseline in Integrated Alzheimer's Disease Rating Scale (iADRS) Score at Weeks 78 and 106 [ Time Frame: Baseline, 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.
2.	Change From Baseline in ADCS-ADL-MCI Score at Weeks 78 and 106 [ Time Frame: Baseline, 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.
3.	Change From Baseline in ADAS-Cog13 Score at Weeks 78 and 106 [ Time Frame: Baseline, 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.
4.	Change From Baseline in Mini-Mental State Examination (MMSE) Score at Weeks 78 and 106 [ Time Frame: Baseline, 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.
5.	Change From Baseline in Neuropsychiatric Inventory-10 (NPI-10) Score at Weeks 78 and 106 [ Time Frame: Baseline, 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.
6.	Change From Baseline in Amyloid Positron Emission Tomography (PET) Signal at Weeks 78 and 104 [ Time Frame: Baseline, Weeks 78 and 104 ] The cerebral amyloid plaque level was measured by amyloid PET imaging.
7.	Change From Baseline in Tau PET Signal at Weeks 78 and 104 [ Time Frame: Baseline, Weeks 78 and 104 ] The cerebral tau level was measured by tau PET imaging.
8.	Change From Baseline in CDR-SB Score at Week 106 [ Time Frame: Baseline, 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.
9.	Change From Baseline in Global Statistical Test (GST) Composite Z-Score [ Time Frame: Baseline, Weeks 78 and 106 ] 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.

Eligibility


Minimum Age:	60 Years
Maximum Age:	85 Years
Sex:	All
Gender Based:
Accepts Healthy Volunteers:	No
Criteria:	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 Have an MMSE score between 22 and 30 inclusive Have a CDR memory score >0.5 Have a Clinical Dementia Rating Scale Global Score (CDR-GS) of 0.5 or 1.0 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 ε4 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

Contacts/Locations


Central Contact Person:	US Biogen Clinical Trial Center Telephone: 866-633-4636 Email: clinicaltrials@biogen.com
Central Contact Backup:	Global Biogen Clinical Trial Center Email: clinicaltrials@biogen.com
Study Officials:	Medical Director Study Director Biogen
Locations:

IPDSharing


Plan to Share IPD:	Yes In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on http://clinicalresearch.biogen.com/
	Supporting Information:
	Time Frame:
	Access Criteria:
	URL: https://vivli.org/

References


Citations:
Links:
Available IPD/Information: