Cognitive DysfunctionPhase 2EVOLVENCT03639987
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
A Phase 2 study testing Aducanumab in people with Cognitive Dysfunction and Alzheimer's Disease, run by Biogen at 22 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 50 to 85 years
- Conditions the study is for
- Cognitive Dysfunction, Alzheimer's Disease
- What is being tested?
- Aducanumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 52 participants
- Where
- 22 sitesUnited States
- Study dates
- 20 Dec 2018to 30 Jul 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)).
Who cannot join
- 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
Trial locations and contacts
22 sites in 1 country.
22 sites in 1 country
United States22 sites
JEM Research Institute
Atlantis, Florida, 33462
Senior Adult Specialty Research
Austin, Texas, 78757
Medical Research Health and Education Foundation, Inc
Columbus, Georgia, 31909
Neurology Clinic, PC
Cordova, Tennessee, 38108
Brain Matters Research
Delray Beach, Florida, 33445
Neuropsychiatric Research Center of Southwest Florida
Fort Myers, Florida, 33912
Neurology Center of North Orange County
Fullerton, California, 92835
Baylor College Of Medicine
Houston, Texas, 77030
Clinical Trial Network
Houston, Texas, 77074
Josephson, Wallack, Munshower Neurology, P.C.
Indianapolis, Indiana, 46256
Las Vegas Medical Research
Las Vegas, Nevada, 89113
Lynn Health Science Institute
Oklahoma City, Oklahoma, 73112
Bioclinica Orlando
Orlando, Florida, 32806
Pacific Neuroscience Medical Group
Oxnard, California, 93030
Banner Alzheimer's Institute
Phoenix, Arizona, 85006
National Clinical Research Inc.-Richmond
Richmond, Virginia, 23294
Pacific Research Network, Inc
San Diego, California, 92103
California Neuroscience Research Medical Group Inc.
Sherman Oaks, California, 91403
Kingfisher Cooperative, LLC
Spokane, Washington, 99202
Bioclinica Orlando
The Villages, Florida, 32162
Advanced Memory Research Institute of NJ, PC
Toms River, New Jersey, 08755
Center for Neurosciences
Tucson, Arizona, 85718
About this study
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
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.
- Conditions
- Cognitive Dysfunction, Alzheimer's Disease
- Being tested
- Aducanumab, Placebo
- Keywords
- Aducanumab, BIIB037
- Medical subject headings
- Cognitive Dysfunction, Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AducanumabDrug
Also called BIIB037
Administered as specified in the treatment arm.
PlaceboDrug
Administered as specified in the treatment arm.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | 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. Receives: Drug: Aducanumab; Drug: Placebo |
| Group 2 | Experimental | 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. Receives: Drug: Aducanumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Clinically Impactful Amyloid-related Imaging Abnormalities (ARIA)
Measured: up to Week 54
Secondary outcomes (10)
Number of Participants With ARIA by Severity as Obtained on Magnetic Resonance Imaging (MRI)
ARIA by severity was obtained on Magnetic Resonance Imaging (MRI).
Measured: up to Week 54
Time to Onset of ARIA as Obtained on MRI
Measured: up to Week 54
Time to Resolution of ARIA as Obtained on MRI
Measured: up to Week 54
Number of Participants With Symptomatic ARIA by Severity
ARIA by severity was obtained on Magnetic Resonance Imaging (MRI).
Measured: up to Week 54
Time to Onset of Symptomatic ARIA
Measured: up to Week 54
Time to Resolution of Symptomatic ARIA
Measured: up to Week 54
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.
Measured: up to Week 54
Change From Baseline in the Montreal Cognitive Assessment (MoCA) at Week 54
Measured: Baseline, Week 54
Number of Participants With Aducanumab Concentration in Serum
Measured: up to Week 54
Number of Participants With Antiaducanumab Antibodies in Serum
Measured: up to Week 54
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2018
- Study start20 Dec 2018
- Primary completion30 Jul 2019
- Study completion30 Jul 2019
Why it stopped: Study was discontinued based on futility analysis conducted on Phase 3 trials (NCT02477800 and NCT02484547) and not based on safety concerns.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Cognitive DysfunctionStudies of the same condition, open and under way.
- More trials run by BiogenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- Biogen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Biogen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03639987
- Sponsor's protocol ID
- 221AD205
- Other IDs
- 2018-002102-31, 2018
- Acronym
- EVOLVE
- Status last verified
- Aug 2021
- First submitted
- 17 Aug 2018
- Last updated
- 16 Sep 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03639987
- Acronym / sponsor ID
- EVOLVE / 221AD205
- Conditions
- Cognitive Dysfunction, Alzheimer's Disease
- Keywords
- Aducanumab, BIIB037
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was discontinued based on futility analysis conducted on Phase 3 trials (NCT02477800 and NCT02484547) and not based on safety concerns.
- Enrolment
- 52 participants (actual)
- Lead sponsor
- BiogenIndustry (pharma, biotech, devices)
- Study start
- 20 Dec 2018 (actual)
- Primary completion
- 30 Jul 2019 (actual)
- Study completion
- 30 Jul 2019 (actual)
- First posted
- 21 Aug 2018 (actual)
- Results
- Posted 16 Sep 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Drug: Aducanumab, Drug: PlaceboAducanumab, 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. |
| Group 2 | Experimental | Drug: AducanumabAducanumab, 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. |
Who may qualify
- Ages
- 50 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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 (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AducanumabAlso: BIIB037Administered as specified in the treatment arm. | Drug | Group 1, Group 2 |
| PlaceboAdministered as specified in the treatment arm. | Drug | Group 1 |
Primary outcome
Number of Participants With Clinically Impactful Amyloid-related Imaging Abnormalities (ARIA)
Time frame: up to Week 54
10 secondary outcomes
Number of Participants With ARIA by Severity as Obtained on Magnetic Resonance Imaging (MRI)
Time frame: up to Week 54
Time to Onset of ARIA as Obtained on MRI
Time frame: up to Week 54
Time to Resolution of ARIA as Obtained on MRI
Time frame: up to Week 54
Number of Participants With Symptomatic ARIA by Severity
Time frame: up to Week 54
Time to Onset of Symptomatic ARIA
Time frame: up to Week 54
Time to Resolution of Symptomatic ARIA
Time frame: up to Week 54
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: up to Week 54
Change From Baseline in the Montreal Cognitive Assessment (MoCA) at Week 54
Time frame: Baseline, Week 54
Number of Participants With Aducanumab Concentration in Serum
Time frame: up to Week 54
Number of Participants With Antiaducanumab Antibodies in Serum
Time frame: up to Week 54
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Biogen
22 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Aducanumab in people with Cognitive Dysfunction and Alzheimer's Disease, run by Biogen at 22 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 16 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Sep 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Clinically Impactful Amyloid-related Imaging Abnormalities (ARIA) (time frame: up to Week 54). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Sep 2021.