Alzheimer's Disease
Conditions
Brief summary
The primary objective is to evaluate the safety and tolerability of aducanumab over 100 weeks of treatment after a wash-out period imposed by discontinuation of feeder studies in participants who had previously received aducanumab (i.e. previously treated participants) or who had previously received placebo (i.e. treatment-naïve participants).
Interventions
DRUGAducanumab
Administered as specified in the treatment arm.
Sponsors
Biogen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: Core Treatment Period: * Participant was participating in an aducanumab clinical study at the time of the announcement of early termination (feeder studies). * Has one care partner who, in the Investigator's opinion, has adequate contact with the participant as to be able to provide accurate information about the participant's cognitive and functional abilities. LTE Treatment Period: * Participant must have completed the Core study period (Week 102) and adequately tolerated 10 mg/kg of aducanumab during the Core study period in the opinion of the Investigator. * Has one informant/care partner who, in the Investigator's opinion, has frequent and sufficient contact with the participant as to be able to provide accurate information about the participant's cognitive and functional abilities. Key
Exclusion criteria
Core Treatment Period: * Any medical or neurological condition (other than Alzheimer's Disease) that might be a contributing cause of the participant's cognitive impairment. * Stroke or any unexplained loss of consciousness within 1 year prior to Screening. * Clinically significant unstable psychiatric illness in past 6 months. * History of unstable angina, myocardial infarction, advanced chronic heart failure, or clinically significant conduction abnormalities within 1 year prior to Screening. * A seizure event that occurred after the last visit of the feeder study and before Screening for this study. * Evidence of impaired liver function as shown by an abnormal liver function profile at Screening. * History of or known seropositivity for HIV. * Clinically significant systemic illness or serious infection within 30 days prior to or during Screening. * Contraindications to having a brain magnetic resonance imaging (MRI). LTE Treatment Period: * Any medical or psychiatric contraindication or clinically significant abnormality that, in the opinion of the Investigator, will substantially increase the risk associated with the participant's enrollment in and completion of the study. Note- Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Core Treatment Period: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | From the first dose of study drug to end of follow-up (up to Week 118) | An AE is any untoward medical occurrence in a participant/clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of medicinal(investigational) product, whether or not related to medicinal (investigational) product. An 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 significant disability/incapacity or congenital anomaly, is medically important event. TEAE or Serious TEAEs are defined as any AE that has an onset date and time that is on or after date and time of first dose of study treatment, or that has worsened after date and time of first dose of study treatment. |
| Core Treatment Period: Number of Participants With AEs Leading to Treatment Discontinuation (TD) and Study Withdrawal (SW) | From the first dose of study drug to end of follow-up (up to Week 118) | 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. |
| Core Treatment Period: Number of Participants With Amyloid-Related Imaging Abnormality-Edema (ARIA-E) | Up to Week 118 | Number of participants diagnosed with ARIA edema are reported. |
| Core Treatment Period: Number of Participants With Amyloid-Related Imaging Abnormality- Hemorrhage or Superficial Siderosis (ARIA-H) | Up to Week 118 | Number of participants diagnosed with ARIA hemmorrhage or superficial siderosis are reported. |
| Core Treatment Period: Number of Participants With Positive Antidrug Antibodies (ADAs) in Serum | Up to Week 102 | The presence of serum ADAs was determined using a validated assay. A standard 3-tiered approach was used including screening assay, confirmatory assay, and titration assay. The number of participants with a positive response to ADAs are reported. |
Countries
Australia, Austria, Belgium, Canada, Denmark, Finland, France, Germany, Italy, Japan, Netherlands, Poland, Portugal, South Korea, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
Participants took part in the study at the investigative sites in the United States, Australia, Austria, Belgium, Canada, Denmark, Finland, France, Germany, Italy, Japan, South Korea, Netherlands, Poland, Portugal, Spain, Sweden, Switzerland, Taiwan, and United Kingdom from 02 Mar 2020 to 22 Jul 2024.
Pre-assignment details
A total of 1696 participants were enrolled and treated in the core period, of which 1118 participants completed the core period. Out of the participants who completed the core period, 1041 participants entered the long-term extension (LTE) period, and 508 participants completed the LTE period.
Participants by arm
| Arm | Count |
|---|---|
| Aducanumab Participants were administered aducanumab 10 mg/kg by IV infusions, Q4W for 100 weeks during the Core Treatment Period. Eligible participants continued to receive aducanumab 10 mg/kg IV infusion, Q4W, for 52 weeks during the LTE Treatment Period. | 1,696 |
| Total | 1,696 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Core Treatment Period | Adverse Event | 91 |
| Core Treatment Period | Change of Treatment | 4 |
| Core Treatment Period | Consent Withdrawn | 143 |
| Core Treatment Period | Death | 26 |
| Core Treatment Period | Disease Progression | 67 |
| Core Treatment Period | Investigator Decision | 40 |
| Core Treatment Period | Loss of Capacity | 9 |
| Core Treatment Period | Lost to Follow-up | 11 |
| Core Treatment Period | Missing | 2 |
| Core Treatment Period | Reason Not Specified | 41 |
| Core Treatment Period | Relocation | 4 |
| Core Treatment Period | Study Terminated by Sponsor | 1 |
| Core Treatment Period | Study Visit Burden | 40 |
| Core Treatment Period | Withdrawal by Guardian/caretaker | 99 |
| LTE Period | Adverse Event | 19 |
| LTE Period | Change of Treatment | 1 |
| LTE Period | Consent Withdrawn | 71 |
| LTE Period | Death | 8 |
| LTE Period | Disease Progression | 11 |
| LTE Period | Investigator Decision | 12 |
| LTE Period | Loss of Capacity | 2 |
| LTE Period | Lost to Follow-up | 7 |
| LTE Period | Reason Not Specified | 65 |
| LTE Period | Relocation | 6 |
| LTE Period | Site Terminated by Sponsor | 26 |
| LTE Period | Study Terminated by Sponsor | 276 |
| LTE Period | Study Visit Burden | 10 |
| LTE Period | Withdrawal by Guardian/caretaker | 19 |
Baseline characteristics
| Characteristic | Aducanumab |
|---|---|
| Age, Continuous | 73.1 years STANDARD_DEVIATION 7.34 |
| Race/Ethnicity, Customized Ethnicity Hispanic or Latino | 61 Participants |
| Race/Ethnicity, Customized Ethnicity Not Hispanic or Latino | 1562 Participants |
| Race/Ethnicity, Customized Ethnicity Not Reported Due to Confidentiality Regulations | 73 Participants |
| Race/Ethnicity, Customized Race Asian | 185 Participants |
| Race/Ethnicity, Customized Race Black or African American | 8 Participants |
| Race/Ethnicity, Customized Race Not Reported Due to Confidentiality Regulations | 55 Participants |
| Race/Ethnicity, Customized Race Other | 3 Participants |
| Race/Ethnicity, Customized Race Unknown | 46 Participants |
| Race/Ethnicity, Customized Race White | 1399 Participants |
| Sex: Female, Male Female | 881 Participants |
| Sex: Female, Male Male | 815 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 37 / 1,696 |
| other Total, other adverse events | 1,351 / 1,696 |
| serious Total, serious adverse events | 416 / 1,696 |
Outcome results
Primary
Core Treatment Period: Number of Participants With AEs Leading to Treatment Discontinuation (TD) and Study Withdrawal (SW)
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.
Time frame: From the first dose of study drug to end of follow-up (up to Week 118)
Population: The safety population for the core period included all participants who had received at least one dose of aducanumab in the core period.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Aducanumab | Core Treatment Period: Number of Participants With AEs Leading to Treatment Discontinuation (TD) and Study Withdrawal (SW) | AEs leading to TD | 168 Participants |
| Aducanumab | Core Treatment Period: Number of Participants With AEs Leading to Treatment Discontinuation (TD) and Study Withdrawal (SW) | AEs leading to SW | 129 Participants |
Primary
Core Treatment Period: Number of Participants With Amyloid-Related Imaging Abnormality-Edema (ARIA-E)
Number of participants diagnosed with ARIA edema are reported.
Time frame: Up to Week 118
Population: The safety magnetic resonance imaging (MRI) population for the core period included all participants who had received at least one dose of aducanumab in the core period and had at least one post-baseline MRI assessment in the core period. Here, 'overall number of participants analyzed' signifies the number of participants with data available for outcome measure analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aducanumab | Core Treatment Period: Number of Participants With Amyloid-Related Imaging Abnormality-Edema (ARIA-E) | 422 Participants |
Primary
Core Treatment Period: Number of Participants With Amyloid-Related Imaging Abnormality- Hemorrhage or Superficial Siderosis (ARIA-H)
Number of participants diagnosed with ARIA hemmorrhage or superficial siderosis are reported.
Time frame: Up to Week 118
Population: The safety MRI population for the core period included all participants who had received at least one dose of aducanumab in the core period and had at least one post-baseline MRI assessment in the core period. Here, 'overall number of participants analyzed' signifies the number of participants with data available for outcome measure analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aducanumab | Core Treatment Period: Number of Participants With Amyloid-Related Imaging Abnormality- Hemorrhage or Superficial Siderosis (ARIA-H) | 505 Participants |
Primary
Core Treatment Period: Number of Participants With Positive Antidrug Antibodies (ADAs) in Serum
The presence of serum ADAs was determined using a validated assay. A standard 3-tiered approach was used including screening assay, confirmatory assay, and titration assay. The number of participants with a positive response to ADAs are reported.
Time frame: Up to Week 102
Population: The immunogenicity population for the core period included all participants who had received at least one dose of aducanumab in the core period and had at least one post-dose sample evaluated for immunogenicity in the core period. Here, 'overall number of participants analyzed' signifies the number of participants with data available for outcome measure analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aducanumab | Core Treatment Period: Number of Participants With Positive Antidrug Antibodies (ADAs) in Serum | 19 Participants |
Primary
Core Treatment Period: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
An AE is any untoward medical occurrence in a participant/clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of medicinal(investigational) product, whether or not related to medicinal (investigational) product. An 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 significant disability/incapacity or congenital anomaly, is medically important event. TEAE or Serious TEAEs are defined as any AE that has an onset date and time that is on or after date and time of first dose of study treatment, or that has worsened after date and time of first dose of study treatment.
Time frame: From the first dose of study drug to end of follow-up (up to Week 118)
Population: The safety population for the core period included all participants who had received at least one dose of aducanumab in the core period.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Aducanumab | Core Treatment Period: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 1549 Participants |
| Aducanumab | Core Treatment Period: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 318 Participants |