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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03639987




Registration number
NCT03639987
Ethics application status
Date submitted
17/08/2018
Date registered
21/08/2018
Date last updated
16/04/2019

Titles & IDs
Public 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
Scientific 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
Secondary ID [1] 0 0
2018-002102-31
Secondary ID [2] 0 0
221AD205
Universal Trial Number (UTN)
Trial acronym
EVOLVE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cognitive Dysfunction 0 0
Alzheimer's Disease 0 0
Condition category
Condition code
Neurological 0 0 0 0
Alzheimer's disease
Neurological 0 0 0 0
Dementias
Mental Health 0 0 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Aducanumab
Treatment: Drugs - Placebo

Experimental: Group 1 - 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.

Experimental: Group 2 - 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.


Treatment: Drugs: Aducanumab
Administered as specified in the treatment arm.

Treatment: Drugs: Placebo
Administered as specified in the treatment arm.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Clinically Impactful Amyloid-related Imaging Abnormalities (ARIA) - Clinically impactful ARIA is defined as symptoms and/or signs associated with ARIA that meet pre-defined criteria as assessed by an independent adjudication committee.
Timepoint [1] 0 0
Baseline up to Week 54
Secondary outcome [1] 0 0
Number of Participants With ARIA by Severity as Obtained on Magnetic Resonance Imaging (MRI) - Severity of ARIA is graded as mild, moderate and severe.
Timepoint [1] 0 0
Baseline up to Week 54
Secondary outcome [2] 0 0
Time to Onset of ARIA as Obtained on MRI - Time to onset of ARIA is defined as the time from first dose until the first subsequent documentation of onset of ARIA as obtained on MRI.
Timepoint [2] 0 0
Baseline up to Week 54
Secondary outcome [3] 0 0
Time to Resolution of ARIA as Obtained on MRI - Time to resolution of ARIA is defined as the time from first onset until the first subsequent documentation of resolution of ARIA as obtained on MRI.
Timepoint [3] 0 0
Baseline up to Week 54
Secondary outcome [4] 0 0
Number of Participants With Symptomatic ARIA by Severity - Severity of symptomatic ARIA to be graded as mild, moderate and severe.
Timepoint [4] 0 0
Baseline up to Week 54
Secondary outcome [5] 0 0
Time to Onset of Symptomatic ARIA - Time to onset of symptomatic ARIA is defined as the time from first dose until the first subsequent documentation of onset of ARIA.
Timepoint [5] 0 0
Baseline up to Week 54
Secondary outcome [6] 0 0
Time to Resolution of Symptomatic ARIA - Time to resolution of symptomatic ARIA is defined as the time from first onset until the first subsequent documentation of resolution of symptomatic ARIA.
Timepoint [6] 0 0
Baseline up to Week 54
Secondary outcome [7] 0 0
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) - An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A SAE is any untoward medical occurrence that at any dose results in death, is a life-threatening event, requires inpatient hospitalization or prolongation of existing hospitalization, results in a significant disability/incapacity or congenital anomaly, is a medically important event.
Timepoint [7] 0 0
Baseline up to Week 54
Secondary outcome [8] 0 0
Change From Baseline in the Montreal Cognitive Assessment (MoCA) at Week 54 - MoCA is used to assess changes in cognition.
Timepoint [8] 0 0
Baseline, Week 54
Secondary outcome [9] 0 0
Aducanumab Concentration in Serum
Timepoint [9] 0 0
Pre-dose on Day 1 of Weeks 1, 16, 24, 32, 44, 54, 56, 70, 80, 104
Secondary outcome [10] 0 0
Number of Participants With Antiaducanumab Antibodies in Serum - Presence of serum antiaducanumab antibodies will be determined using a validated assay.
Timepoint [10] 0 0
Pre-dose on Day 1 of Weeks 1, 16, 24, 32, 44, 54, 56, 70, 80, 104

Eligibility
Key inclusion criteria
Inclusion/
Minimum age
50 Years
Maximum age
85 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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 Aß 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

- 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
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
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
Australian Alzheimer's Research Foundation Incorporated - Nedlands
Recruitment postcode(s) [1] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Indiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Nevada
Country [7] 0 0
United States of America
State/province [7] 0 0
New Jersey
Country [8] 0 0
United States of America
State/province [8] 0 0
Oklahoma
Country [9] 0 0
United States of America
State/province [9] 0 0
Tennessee
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
United States of America
State/province [11] 0 0
Virginia
Country [12] 0 0
United States of America
State/province [12] 0 0
Washington
Country [13] 0 0
Canada
State/province [13] 0 0
British Columbia
Country [14] 0 0
Canada
State/province [14] 0 0
Ontario
Country [15] 0 0
Italy
State/province [15] 0 0
Palermo
Country [16] 0 0
Italy
State/province [16] 0 0
Milano
Country [17] 0 0
Spain
State/province [17] 0 0
Catalonia
Country [18] 0 0
Spain
State/province [18] 0 0
Córdoba

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Biogen
Address
Country

Ethics approval
Ethics application status

Summary
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.

Study was discontinued based on futility analysis conducted on Phase 3 trials (NCT02477800
and NCT02484547) and not based on safety concerns. Follow-up visits and closing out study
activities in progress.
Trial website
https://clinicaltrials.gov/show/NCT03639987
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Biogen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications