Back to resultsA Study of Aducanumab in Participants With Mild Cognitive Impairment Due to Alzheimer's Disease or With Mild Alzheimer's Disease Dementia to Evaluate the Safety of Continued Dosing in Participants With Asymptomatic Amyloid-Related Imaging Abnormalities (EVOLVE)
Primary Purpose
Cognitive Dysfunction, Alzheimer's Disease
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Aducanumab
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Cognitive Dysfunction focused on measuring Aducanumab, BIIB037
Eligibility Criteria
Inclusion/ Exclusion Criteria
Key Inclusion Criteria:
- Ability of the participant or his/her legally authorized representative to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use confidential health information in accordance with national and local participant privacy regulations.
- Must have at least 6 years of education or work experience to exclude mental deficits other than MCI due to AD or mild AD dementia.
- Must have evidence of cerebral Aβ accumulation, based on a positive PET scan of the brain. Previously obtained positron emission tomography (PET) scan (within 12 months of screening) is permissible. Previous PET scan images must be submitted to the central imaging vendor to confirm that study inclusion criteria are met.
- Must consent to apolipoprotein E (ApoE) genotyping.
- Must meet all of the following clinical criteria for MCI due to AD or mild AD dementia according to NIA-AA criteria [Albert 2011; McKhann 2011], and must have the following: MCI due to AD (a CDR global score of 0.5, and an MMSE score between 24 and 30 (inclusive)), or Mild AD dementia (a CDR global score of 0.5 or 1, and as MMSE score between 20 and 26 (inclusive)).
Key Exclusion Criteria:
- Any uncontrolled medical or neurological/neurodegenerative condition (other than AD) that, in the opinion of the Investigator, might be a contributing cause of the participant's cognitive impairment (e.g., substance abuse, vitamin B12 deficiency, abnormal thyroid function, stroke or other cerebrovascular condition, Lewy body dementia, frontotemporal dementia, head trauma).
- Clinically significant unstable psychiatric illness (e.g., uncontrolled major depression, uncontrolled schizophrenia, uncontrolled bipolar affective disorder) within 6 months prior to Screening.
- Transient ischemic attack or stroke or any unexplained loss of consciousness within 1 year prior to Screening.
- Vaccinations within 10 days prior to randomization (Day 1).
- Female participants who are pregnant or currently breastfeeding.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply
Sites / Locations
- Banner Alzheimer's Institute
- Center for Neurosciences
- Neurology Center of North Orange County
- Pacific Neuroscience Medical Group
- Pacific Research Network, Inc
- California Neuroscience Research Medical Group Inc.
- JEM Research Institute
- Brain Matters Research
- Neuropsychiatric Research Center of Southwest Florida
- Bioclinica Orlando
- Bioclinica Orlando
- Medical Research Health and Education Foundation, Inc
- Josephson, Wallack, Munshower Neurology, P.C.
- Las Vegas Medical Research
- Advanced Memory Research Institute of NJ, PC
- Lynn Health Science Institute
- Neurology Clinic, PC
- Senior Adult Specialty Research
- Baylor College Of Medicine
- Clinical Trial Network
- National Clinical Research Inc.-Richmond
- Kingfisher Cooperative, LLC
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Group 1
Group 2
Arm Description
Aducanumab, intravenous infusion, every 4 weeks for up to Week 52 during the randomized treatment period. The dose will be titrated to a desirable dose. Participants will be managed for drug continuation and suspension. Following a 4-week follow-up period, eligible participants will continue to receive aducanumab, intravenous infusion, every 4 weeks for an additional 104 weeks in the long-term extension period.
Aducanumab, intravenous infusion, every 4 weeks for up to Week 52 during the randomized treatment period. The dose will be titrated to a desirable dose. Participants will be managed for drug continuation and suspension. Following a 4-week follow-up period, eligible participants will continue to receive aducanumab, intravenous infusion, every 4 weeks for an additional 104 weeks in the long-term extension period.
Outcomes
Primary Outcome Measures
Number of Participants With Clinically Impactful Amyloid-related Imaging Abnormalities (ARIA)
Secondary Outcome Measures
Number of Participants With ARIA by Severity as Obtained on Magnetic Resonance Imaging (MRI)
ARIA by severity was obtained on Magnetic Resonance Imaging (MRI).
Time to Onset of ARIA as Obtained on MRI
Time to Resolution of ARIA as Obtained on MRI
Number of Participants With Symptomatic ARIA by Severity
ARIA by severity was obtained on Magnetic Resonance Imaging (MRI).
Time to Onset of Symptomatic ARIA
Time to Resolution of Symptomatic ARIA
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that at any dose: results in death, in the view of the Investigator, places the participant at immediate risk of death (a life-threatening event), however, this does not include an event that, had it occurred in a more severe form, might have caused death; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect or is a medically important event.
Change From Baseline in the Montreal Cognitive Assessment (MoCA) at Week 54
Number of Participants With Aducanumab Concentration in Serum
Number of Participants With Antiaducanumab Antibodies in Serum
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03639987
Brief Title
A Study of Aducanumab in Participants With Mild Cognitive Impairment Due to Alzheimer's Disease or With Mild Alzheimer's Disease Dementia to Evaluate the Safety of Continued Dosing in Participants With Asymptomatic Amyloid-Related Imaging Abnormalities
Acronym
EVOLVE
Official Title
A Phase 2, Multicenter, Randomized, Parallel-Group, Double-Blind, Controlled Study of Aducanumab (BIIB037) in Subjects With Mild Cognitive Impairment Due to Alzheimer's Disease or With Mild Alzheimer's Disease Dementia to Evaluate the Safety of Continued Dosing in Subjects With Asymptomatic Amyloid-Related Imaging Abnormalities
Study Type
Interventional
2. Study Status
Record Verification Date
August 2021
Overall Recruitment Status
Terminated
Why Stopped
Study was discontinued based on futility analysis conducted on Phase 3 trials (NCT02477800 and NCT02484547) and not based on safety concerns.
Study Start Date
December 20, 2018 (Actual)
Primary Completion Date
July 30, 2019 (Actual)
Study Completion Date
July 30, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biogen
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The primary objective of the study is to assess the safety impact of continuing aducanumab dosing in asymptomatic Amyloid-related Imaging Abnormalities (ARIA) in participants with mild cognitive impairment (MCI) due to Alzheimer's disease (AD) or with mild AD dementia. The secondary objective of the study is to characterize ARIA, from both the imaging and the clinical perspective and to characterize the safety, tolerability, pharmacokinetics (PK), and immunogenicity of aducanumab.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cognitive Dysfunction, Alzheimer's Disease
Keywords
Aducanumab, BIIB037
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
52 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group 1
Arm Type
Experimental
Arm Description
Aducanumab, intravenous infusion, every 4 weeks for up to Week 52 during the randomized treatment period. The dose will be titrated to a desirable dose. Participants will be managed for drug continuation and suspension. Following a 4-week follow-up period, eligible participants will continue to receive aducanumab, intravenous infusion, every 4 weeks for an additional 104 weeks in the long-term extension period.
Arm Title
Group 2
Arm Type
Experimental
Arm Description
Aducanumab, intravenous infusion, every 4 weeks for up to Week 52 during the randomized treatment period. The dose will be titrated to a desirable dose. Participants will be managed for drug continuation and suspension. Following a 4-week follow-up period, eligible participants will continue to receive aducanumab, intravenous infusion, every 4 weeks for an additional 104 weeks in the long-term extension period.
Intervention Type
Drug
Intervention Name(s)
Aducanumab
Other Intervention Name(s)
BIIB037
Intervention Description
Administered as specified in the treatment arm.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Administered as specified in the treatment arm.
Primary Outcome Measure Information:
Title
Number of Participants With Clinically Impactful Amyloid-related Imaging Abnormalities (ARIA)
Time Frame
up to Week 54
Secondary Outcome Measure Information:
Title
Number of Participants With ARIA by Severity as Obtained on Magnetic Resonance Imaging (MRI)
Description
ARIA by severity was obtained on Magnetic Resonance Imaging (MRI).
Time Frame
up to Week 54
Title
Time to Onset of ARIA as Obtained on MRI
Time Frame
up to Week 54
Title
Time to Resolution of ARIA as Obtained on MRI
Time Frame
up to Week 54
Title
Number of Participants With Symptomatic ARIA by Severity
Description
ARIA by severity was obtained on Magnetic Resonance Imaging (MRI).
Time Frame
up to Week 54
Title
Time to Onset of Symptomatic ARIA
Time Frame
up to Week 54
Title
Time to Resolution of Symptomatic ARIA
Time Frame
up to Week 54
Title
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that at any dose: results in death, in the view of the Investigator, places the participant at immediate risk of death (a life-threatening event), however, this does not include an event that, had it occurred in a more severe form, might have caused death; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect or is a medically important event.
Time Frame
up to Week 54
Title
Change From Baseline in the Montreal Cognitive Assessment (MoCA) at Week 54
Time Frame
Baseline, Week 54
Title
Number of Participants With Aducanumab Concentration in Serum
Time Frame
up to Week 54
Title
Number of Participants With Antiaducanumab Antibodies in Serum
Time Frame
up to Week 54
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion/ Exclusion Criteria
Key Inclusion Criteria:
Ability of the participant or his/her legally authorized representative to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use confidential health information in accordance with national and local participant privacy regulations.
Must have at least 6 years of education or work experience to exclude mental deficits other than MCI due to AD or mild AD dementia.
Must have evidence of cerebral Aβ accumulation, based on a positive PET scan of the brain. Previously obtained positron emission tomography (PET) scan (within 12 months of screening) is permissible. Previous PET scan images must be submitted to the central imaging vendor to confirm that study inclusion criteria are met.
Must consent to apolipoprotein E (ApoE) genotyping.
Must meet all of the following clinical criteria for MCI due to AD or mild AD dementia according to NIA-AA criteria [Albert 2011; McKhann 2011], and must have the following: MCI due to AD (a CDR global score of 0.5, and an MMSE score between 24 and 30 (inclusive)), or Mild AD dementia (a CDR global score of 0.5 or 1, and as MMSE score between 20 and 26 (inclusive)).
Key Exclusion Criteria:
Any uncontrolled medical or neurological/neurodegenerative condition (other than AD) that, in the opinion of the Investigator, might be a contributing cause of the participant's cognitive impairment (e.g., substance abuse, vitamin B12 deficiency, abnormal thyroid function, stroke or other cerebrovascular condition, Lewy body dementia, frontotemporal dementia, head trauma).
Clinically significant unstable psychiatric illness (e.g., uncontrolled major depression, uncontrolled schizophrenia, uncontrolled bipolar affective disorder) within 6 months prior to Screening.
Transient ischemic attack or stroke or any unexplained loss of consciousness within 1 year prior to Screening.
Vaccinations within 10 days prior to randomization (Day 1).
Female participants who are pregnant or currently breastfeeding.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Biogen
Official's Role
Study Director
Facility Information:
Facility Name
Banner Alzheimer's Institute
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85006
Country
United States
Facility Name
Center for Neurosciences
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85718
Country
United States
Facility Name
Neurology Center of North Orange County
City
Fullerton
State/Province
California
ZIP/Postal Code
92835
Country
United States
Facility Name
Pacific Neuroscience Medical Group
City
Oxnard
State/Province
California
ZIP/Postal Code
93030
Country
United States
Facility Name
Pacific Research Network, Inc
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Facility Name
California Neuroscience Research Medical Group Inc.
City
Sherman Oaks
State/Province
California
ZIP/Postal Code
91403
Country
United States
Facility Name
JEM Research Institute
City
Atlantis
State/Province
Florida
ZIP/Postal Code
33462
Country
United States
Facility Name
Brain Matters Research
City
Delray Beach
State/Province
Florida
ZIP/Postal Code
33445
Country
United States
Facility Name
Neuropsychiatric Research Center of Southwest Florida
City
Fort Myers
State/Province
Florida
ZIP/Postal Code
33912
Country
United States
Facility Name
Bioclinica Orlando
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
Bioclinica Orlando
City
The Villages
State/Province
Florida
ZIP/Postal Code
32162
Country
United States
Facility Name
Medical Research Health and Education Foundation, Inc
City
Columbus
State/Province
Georgia
ZIP/Postal Code
31909
Country
United States
Facility Name
Josephson, Wallack, Munshower Neurology, P.C.
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46256
Country
United States
Facility Name
Las Vegas Medical Research
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89113
Country
United States
Facility Name
Advanced Memory Research Institute of NJ, PC
City
Toms River
State/Province
New Jersey
ZIP/Postal Code
08755
Country
United States
Facility Name
Lynn Health Science Institute
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73112
Country
United States
Facility Name
Neurology Clinic, PC
City
Cordova
State/Province
Tennessee
ZIP/Postal Code
38108
Country
United States
Facility Name
Senior Adult Specialty Research
City
Austin
State/Province
Texas
ZIP/Postal Code
78757
Country
United States
Facility Name
Baylor College Of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Clinical Trial Network
City
Houston
State/Province
Texas
ZIP/Postal Code
77074
Country
United States
Facility Name
National Clinical Research Inc.-Richmond
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23294
Country
United States
Facility Name
Kingfisher Cooperative, LLC
City
Spokane
State/Province
Washington
ZIP/Postal Code
99202
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Study of Aducanumab in Participants With Mild Cognitive Impairment Due to Alzheimer's Disease or With Mild Alzheimer's Disease Dementia to Evaluate the Safety of Continued Dosing in Participants With Asymptomatic Amyloid-Related Imaging Abnormalities
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