Cognitive Dysfunction, Alzheimer's Disease
Conditions
Keywords
Aducanumab, BIIB037
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.
Interventions
DRUGAducanumab
Administered as specified in the treatment arm.
DRUGPlacebo
Administered as specified in the treatment arm.
Sponsors
Biogen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With Clinically Impactful Amyloid-related Imaging Abnormalities (ARIA) | up to Week 54 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Onset of ARIA as Obtained on MRI | up to Week 54 | — |
| Time to Resolution of ARIA as Obtained on MRI | up to Week 54 | — |
| Number of Participants With Symptomatic ARIA by Severity | up to Week 54 | ARIA by severity was obtained on Magnetic Resonance Imaging (MRI). |
| Time to Onset of Symptomatic ARIA | up to Week 54 | — |
| Number of Participants With ARIA by Severity as Obtained on Magnetic Resonance Imaging (MRI) | up to Week 54 | ARIA by severity was obtained on Magnetic Resonance Imaging (MRI). |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | up to Week 54 | 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 | Baseline, Week 54 | — |
| Number of Participants With Aducanumab Concentration in Serum | up to Week 54 | — |
| Number of Participants With Antiaducanumab Antibodies in Serum | up to Week 54 | — |
| Time to Resolution of Symptomatic ARIA | up to Week 54 | — |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at 10 investigative sites in the United States from 20 December 2018 to 30 July 2019.
Pre-assignment details
A total of 52 participants with Alzheimer's disease were enrolled in this study in one of the 2 groups: Group 1 and Group 2 to receive aducanumab titrated up to 10 mg/kg. The groups differed in the protocol specified management rules for amyloid-related imaging abnormalities (ARIA), in the event that moderate or severe asymptomatic ARIA was detected on MRI.
Participants by arm
| Arm | Count |
|---|---|
| Group 1 Aducanumab dose titrated up to 10 mg/kg, IV infusion, following Group 1 ARIA management rules. | 26 |
| Group 2 Aducanumab dose titrated up to 10 mg/kg, IV infusion, following Group 2 ARIA management rules. | 26 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Study terminated by sponsor | 26 | 25 |
Baseline characteristics
| Characteristic | Group 2 | Total | Group 1 |
|---|---|---|---|
| Age, Continuous | 73.3 years STANDARD_DEVIATION 7.14 | 72.9 years STANDARD_DEVIATION 7.09 | 72.5 years STANDARD_DEVIATION 7.17 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 3 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 49 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 26 Participants | 52 Participants | 26 Participants |
| Sex: Female, Male Female | 15 Participants | 29 Participants | 14 Participants |
| Sex: Female, Male Male | 11 Participants | 23 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 0 / 26 |
| other Total, other adverse events | 11 / 26 | 7 / 26 |
| serious Total, serious adverse events | 2 / 26 | 0 / 26 |
Outcome results
Primary
Number of Participants With Clinically Impactful Amyloid-related Imaging Abnormalities (ARIA)
Time frame: up to Week 54
Population: Clinically Impactful ARIA was to be assessed by an independent Adjudication Committee. At the time the study was terminated, the Adjudication Committee had not been formed; therefore, this outcome measure was not evaluated due to lack of data.
Secondary
Change From Baseline in the Montreal Cognitive Assessment (MoCA) at Week 54
Time frame: Baseline, Week 54
Population: Due to early termination of the study, none of the participants reached the week 54 timepoint; therefore, data is not available for analysis.
Secondary
Number of Participants With Aducanumab Concentration in Serum
Time frame: up to Week 54
Population: The safety population is defined as all randomized participants who had received at least one dose of aducanumab.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 | Number of Participants With Aducanumab Concentration in Serum | 1 Participants |
| Group 2 | Number of Participants With Aducanumab Concentration in Serum | 1 Participants |
Secondary
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.
Time frame: up to Week 54
Population: The safety population is defined as all randomized participants who had received at least one dose of aducanumab.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1 | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 15 Participants |
| Group 1 | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 2 Participants |
| Group 2 | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 9 Participants |
| Group 2 | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
Secondary
Number of Participants With Antiaducanumab Antibodies in Serum
Time frame: up to Week 54
Population: The safety population is defined as all randomized participants who received at least one dose of aducanumab.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 | Number of Participants With Antiaducanumab Antibodies in Serum | 0 Participants |
| Group 2 | Number of Participants With Antiaducanumab Antibodies in Serum | 0 Participants |
Secondary
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 frame: up to Week 54
Population: The safety population is defined as all randomized participants who had received at least one dose of aducanumab.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 | Number of Participants With ARIA by Severity as Obtained on Magnetic Resonance Imaging (MRI) | 2 Participants |
| Group 2 | Number of Participants With ARIA by Severity as Obtained on Magnetic Resonance Imaging (MRI) | 0 Participants |
Secondary
Number of Participants With Symptomatic ARIA by Severity
ARIA by severity was obtained on Magnetic Resonance Imaging (MRI).
Time frame: up to Week 54
Population: The safety population is defined as all randomized participants who had received at least one dose of aducanumab.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 | Number of Participants With Symptomatic ARIA by Severity | 1 Participants |
| Group 2 | Number of Participants With Symptomatic ARIA by Severity | 0 Participants |
Secondary
Time to Onset of ARIA as Obtained on MRI
Time frame: up to Week 54
Population: Due to small number of ARIA events, data is not reported due to participant confidentiality/human subjects protection assurances.
Secondary
Time to Onset of Symptomatic ARIA
Time frame: up to Week 54
Population: Due to small number of ARIA events, data is not reported due to participant confidentiality/human subjects protection assurances.
Secondary
Time to Resolution of ARIA as Obtained on MRI
Time frame: up to Week 54
Population: Due to small number of ARIA events, data is not reported due to participant confidentiality/human subjects protection assurances.
Secondary
Time to Resolution of Symptomatic ARIA
Time frame: up to Week 54
Population: Due to small number of ARIA events, data is not reported due to participant confidentiality/human subjects protection assurances.