Trial Outcomes & Findings for A Study to Verify the Clinical Benefit of Aducanumab in Participants With Early Alzheimer's Disease (NCT NCT05310071)

Last Updated: 2025-04-23

Results Overview

The Clinical Dementia Rate Scale integrates assessments from 3 domains of cognition (memory, orientation, judgment/problem-solving) and 3 domains of function (community affairs, home/hobbies, personal care). Following the caregiver interview and systematic participant examination, the rater assigns a score describing the participant's current performance level in each of these domains of life functioning. The "Sum of boxes" scoring methodology sums the score for each of the 6 domains and provides a value ranging from 0 to 18. Higher scores indicate greater impairment. A positive change from baseline indicates greater impairment.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

1027 participants

Primary outcome timeframe

Baseline, Week 78

Results posted on

2025-04-23

Participant Flow

Participants took part in the study at the investigative sites in Australia, Belgium, Brazil, Canada, Finland, France, Germany, Italy, Japan, Mexico, Poland, South Korea, Spain, Sweden, United Kingdom, and United States from 02 Jun 2022 to 12 Aug 2024.

A total of 1027 participants with Alzheimer's Disease (AD) were enrolled and randomized in this study. Of these, 1024 participants were dosed to receive placebo or aducanumab. None of the participants completed the study due to early termination of the study.

Participant milestones

Participant milestones
Measure	Placebo Participants received placebo, once every four weeks (Q4W), administered as an intravenous (IV) infusion.	Aducanumab Participants received aducanumab, up to 10 milligrams per kilogram (mg/kg) of body weight, Q4W, administered as an IV infusion.
Overall Study STARTED	344	680
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	344	680

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received placebo, once every four weeks (Q4W), administered as an intravenous (IV) infusion.	Aducanumab Participants received aducanumab, up to 10 milligrams per kilogram (mg/kg) of body weight, Q4W, administered as an IV infusion.
Overall Study Death	0	3
Overall Study Adverse Event	4	31
Overall Study Lack of Efficacy - Based on Participant Perception	0	2
Overall Study Protocol Deviation	2	0
Overall Study Randomized by Mistake	0	1
Overall Study Failure to Meet Continuation Criteria	2	0
Overall Study Failure to Meet Randomization Criteria	1	2
Overall Study Site Terminated by Sponsor	0	2
Overall Study Study Terminated by Sponsor	282	559
Overall Study Withdrawal by Participant - Study Visit Burden/Scheduling Conflicts	14	17
Overall Study Withdrawal by Participant - Concern About Study Procedures/Perceived Risks	2	6
Overall Study Withdrawal by Participant Relocation (Moving or Has Moved)	1	3
Overall Study Withdrawal by Participant - Desire for Change in Treatment (Unrelated to Safety/Efficacy)	8	17
Overall Study Withdrawal by Participant - Other	25	30
Overall Study Lost to Follow-up	2	4
Overall Study Reason Not Specified	1	3

Baseline Characteristics

A Study to Verify the Clinical Benefit of Aducanumab in Participants With Early Alzheimer's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=344 Participants Participants received placebo, Q4W, administered as an IV infusion.	Aducanumab n=680 Participants Participants received aducanumab, up to 10 mg/kg of body weight, Q4W, administered as an IV infusion.	Total n=1024 Participants Total of all reporting groups
Age, Continuous	72.4 years STANDARD_DEVIATION 6.18 • n=5 Participants	72.2 years STANDARD_DEVIATION 5.81 • n=7 Participants	72.3 years STANDARD_DEVIATION 5.93 • n=5 Participants
Sex: Female, Male Female	187 Participants n=5 Participants	353 Participants n=7 Participants	540 Participants n=5 Participants
Sex: Female, Male Male	157 Participants n=5 Participants	327 Participants n=7 Participants	484 Participants n=5 Participants
Race/Ethnicity, Customized Race · American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian	39 Participants n=5 Participants	73 Participants n=7 Participants	112 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black or African American	3 Participants n=5 Participants	9 Participants n=7 Participants	12 Participants n=5 Participants
Race/Ethnicity, Customized Race · Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	273 Participants n=5 Participants	533 Participants n=7 Participants	806 Participants n=5 Participants
Race/Ethnicity, Customized Race · Not Reported Due to Confidentiality Regulations	26 Participants n=5 Participants	57 Participants n=7 Participants	83 Participants n=5 Participants
Race/Ethnicity, Customized Race · Other	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Race · Multiple: American Indian or Alaska Native and White	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Race · Unknown	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Hispanic or Latino	27 Participants n=5 Participants	51 Participants n=7 Participants	78 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Not Hispanic or Latino	293 Participants n=5 Participants	585 Participants n=7 Participants	878 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Not Reported Due to Confidentiality Regulations	24 Participants n=5 Participants	43 Participants n=7 Participants	67 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Unknown	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 78

Outcome measures

Outcome measures
Measure	Placebo n=6 Participants Participants received placebo, Q4W, administered as IV infusion.	Aducanumab n=8 Participants Participants received aducanumab, up to 10 mg/kg of body weight, Q4W, administered as IV infusion.
Change From Baseline in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) Score at Week 78	0.67 score on a scale Standard Deviation 0.408	1.56 score on a scale Standard Deviation 1.635

SECONDARY outcome

Timeframe: Baseline, Weeks 78 and 106

Population: FAS included all randomized participants who had received at least 1 dose of study treatment (aducanumab or placebo). Here, 'overall number of participants analyzed' signifies the number of participants available for outcome measure analysis. Assessment was also planned for Week 106 for this outcome measure, but no assessments were conducted at Week 106 due to early termination.

The iADRS composite captures a decline in both cognition and daily function. It is a simple linear combination of the Alzheimer's disease assessment scale, cognitive subscale (ADAS-Cog13), and the Alzheimer's disease cooperative study scale for activities of daily living in mild cognitive impairment (ADCS-ADL-MCI). The ADAS-Cog13 scale ranges from 0 to 85 (higher scores indicate worse performance) and the ADCS-ADL-MCI scale ranges from 0 to 53 (higher scores indicate greater independent, healthy functioning). The total score for iADRS scale ranges from 0 to 138, where higher scores indicate better performance.

Outcome measures

Outcome measures
Measure	Placebo n=3 Participants Participants received placebo, Q4W, administered as IV infusion.	Aducanumab n=5 Participants Participants received aducanumab, up to 10 mg/kg of body weight, Q4W, administered as IV infusion.
Change From Baseline in Integrated Alzheimer's Disease Rating Scale (iADRS) Score at Weeks 78 and 106	-14.667 score on a scale Standard Deviation 4.4869	-7.796 score on a scale Standard Deviation 6.7805

SECONDARY outcome

Timeframe: Baseline, Weeks 78 and 106

Population: FAS included all randomized participants who had received at least 1 dose of study treatment (aducanumab or placebo). Here 'overall number of participants analyzed' signifies the number of participants available for outcome measure analysis. Assessment was also planned for Week 106 for this outcome measure, but no assessments were conducted at Week 106 due to early termination.

The ADCS-ADL-MCI scale consists of 17 instrumental items (e.g., shopping, preparing meals, using household appliances, etc) and 1 basic item (getting dressed). Ratings reflect caregiver observations about the participant's actual functioning over the previous month and provide an assessment of change in the functional state of the participant over time. The total score ranges from 0 to 53. Higher scores indicate greater independent, healthy functioning. A positive change from baseline indicates healthy functioning while a negative change from baseline indicates a decline in independent functioning.

Outcome measures

Outcome measures
Measure	Placebo n=3 Participants Participants received placebo, Q4W, administered as IV infusion.	Aducanumab n=5 Participants Participants received aducanumab, up to 10 mg/kg of body weight, Q4W, administered as IV infusion.
Change From Baseline in Alzheimer's Disease Cooperative Study for Activities of Daily Living in Mild Cognitive Impairment (ADCS-ADL-MCI) Scale Score at Weeks 78 and 106	-5.0 score on a scale Standard Deviation 3.61	-0.4 score on a scale Standard Deviation 7.60

SECONDARY outcome

Timeframe: Baseline, Weeks 78 and 106

ADAS-Cog13 comprises both cognitive tasks and clinical ratings of cognitive performance. The cognitive subscale items capture word recall, ability to follow commands, the ability to correctly copy or draw an image, naming, the ability to interact with everyday objects, orientation, word recognition, memory, comprehension of spoken language, word-finding, and language ability, with a measure for delayed word recall and concentration/distractibility. The total score ranges from 0 to 85. Higher scores indicate worse performance. A positive change from baseline indicates decline in cognitive performance.

Outcome measures

Outcome measures
Measure	Placebo n=3 Participants Participants received placebo, Q4W, administered as IV infusion.	Aducanumab n=5 Participants Participants received aducanumab, up to 10 mg/kg of body weight, Q4W, administered as IV infusion.
Change From Baseline in Alzheimer's Disease Assessment Scale, Cognitive Subscale (ADAS-Cog13) at Weeks 78 and 106	9.667 score on a scale Standard Deviation 0.8844	7.396 score on a scale Standard Deviation 2.3262

SECONDARY outcome

Timeframe: Baseline, Weeks 78 and 106

The MMSE scale is a performance-based test of global cognitive status. It consists of 11 tasks that assess orientation, word recall, attention and calculation, language abilities, and visuospatial functions. The scores from the 11 tests are combined to obtain the total score, which ranges from 0 to 30. Higher scores indicate better performance. A negative change from baseline indicates decline in cognitive performance.

Outcome measures

Outcome measures
Measure	Placebo n=3 Participants Participants received placebo, Q4W, administered as IV infusion.	Aducanumab n=5 Participants Participants received aducanumab, up to 10 mg/kg of body weight, Q4W, administered as IV infusion.
Change From Baseline in Mini-Mental State Examination (MMSE) Scale Score at Weeks 78 and 106	-6.0 score on a scale Standard Deviation 1.00	-1.2 score on a scale Standard Deviation 1.48

SECONDARY outcome

Timeframe: Baseline, Weeks 78 and 106

The NPI-10 is a questionnaire administered to the informant, designed to obtain information on the presence of neuropsychiatric symptoms and behaviors in a participant with Alzheimer's disease. Ten areas are assessed: delusions, hallucinations, agitation/aggression, depression, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability and aberrant motor behavior. The NPI total score ranges from 0 to 120. Higher scores indicate greater impairment. A negative change from baseline indicates improvement (symptom reduction).

Outcome measures

Outcome measures
Measure	Placebo n=3 Participants Participants received placebo, Q4W, administered as IV infusion.	Aducanumab n=5 Participants Participants received aducanumab, up to 10 mg/kg of body weight, Q4W, administered as IV infusion.
Change From Baseline in Neuropsychiatric Inventory-10 (NPI-10) Score at Weeks 78 and 106	-8.3 score on a scale Standard Deviation 16.20	-1.8 score on a scale Standard Deviation 6.94

SECONDARY outcome

Timeframe: Baseline, Weeks 78 and 104

Population: FAS included all randomized participants who had received at least 1 dose of study treatment (aducanumab or placebo). Here, 'overall number of participants analyzed' signifies the number of participants available for outcome measure analysis. Due to the decision of early termination, only one participant had an amyloid scan at week 78 and data was reported below. In addition, the assessment planned for Week 104 was not performed due to early termination.

Amyloid PET scan assesses cerebral amyloid load using radiotracers which is standardized into centiloids. Centiloid values on centiloid scale is based on mean composite standardized uptake value ratio (SUVR).

Outcome measures

Outcome measures
Measure	Placebo Participants received placebo, Q4W, administered as IV infusion.	Aducanumab n=1 Participants Participants received aducanumab, up to 10 mg/kg of body weight, Q4W, administered as IV infusion.
Change From Baseline in Amyloid Positron Emission Tomography (PET) Signal at Weeks 78 and 104	—	-2.360 SUVR Standard Deviation NA Since there is only 1 participant analyzed, SD was not estimable.

SECONDARY outcome

Timeframe: Baseline, Weeks 78 and 104

Population: FAS included all randomized participants who had received at least 1 dose of study treatment (aducanumab or placebo). Here, 'overall number of participants analyzed' signifies the number of participants available for outcome measure analysis. Due to decision of early termination, the Tau PET scan was not performed in any participant at scheduled visits of Weeks 78 and 104.

The cerebral tau level was measured by tau PET imaging. Tau PET imaging was conducted using radiotracer. SUVR is a ratio of PET uptake measured in brain region of interest and a disease-free reference region. A higher SUVR is an indication of increased PET radiotracer uptake and worsening disease.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Week 106

Population: Assessment was planned for Week 106 for this outcome measure, but no assessments were conducted at Week 106 due to early termination.

The CDR integrates assessments from 3 domains of cognition (memory, orientation, judgment/problem-solving) and 3 domains of function (community affairs, home/hobbies, personal care). Following caregiver interview and systematic participant examination, the rater assigns a score describing the participant's current performance level in each of these domains of life functioning. The CDR-SB sums the score for each of the 6 domains and provides a value ranging from 0 to 18. Higher scores indicate greater impairment. Positive change from baseline indicates greater impairment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Weeks 78 and 106

GST z-score is an average of z-scores of CDR-SB, ADASCog13 and ADCS-ADL-MCI. CDR-SB assesses 3 cognitive (memory,orientation, judgment/problem-solving)and 3 functional(community affairs,home/hobbies,personal care) domains. Sum of Boxes method combines scores across 6 domains, ranging from 0-18(higher scores=greater impairment). ADAS-Cog13 evaluates cognitive tasks like word recall, naming, orientation and memory, with scores from 0-85 (higher scores=worse performance). ADCS-ADL-MCI rates 17 tasks (e.g.,shopping, preparing meal) and 1 basic task(dressing) with scores from 0-53 (higher scores=greater independence/healthy functioning). z-score\>0 indicates greater impairment/worse performance for CDR-SB and ADASCog13 scales and improved functioning for ADCS-ADL-MCI. For ADCS-ADL-MCI, z-score were reversed (new reversed value=original value-1) to make interpretation consistent. The GST z-score of 0 indicates population mean and score\>0 indicate greater impairment/worse performance.

Outcome measures

Outcome measures
Measure	Placebo n=3 Participants Participants received placebo, Q4W, administered as IV infusion.	Aducanumab n=4 Participants Participants received aducanumab, up to 10 mg/kg of body weight, Q4W, administered as IV infusion.
Change From Baseline in Global Statistical Test (GST) Composite Z-Score at Weeks 78 and 106	0.88 z-score Standard Deviation 0.116	0.48 z-score Standard Deviation 0.515

Adverse Events

Placebo

Serious events: 23 serious events

Other events: 127 other events

Deaths: 0 deaths

Aducanumab

Serious events: 59 serious events

Other events: 359 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=343 participants at risk Participants received placebo, Q4W, administered as IV infusion.	Aducanumab n=681 participants at risk Participants received aducanumab, up to 10 mg/kg of body weight, Q4W, administered as IV infusion.
Infections and infestations Covid-19	5.5% 19/343 • From first dose of study drug up to last follow-up visit (up to approximately 2 years 2 months) Safety analysis set included all randomized participants who had received at least 1 dose of study treatment (aducanumab or placebo). One participant in the placebo arm received drug. This participant was considered in Aducanumab group for safety analysis.	7.2% 49/681 • From first dose of study drug up to last follow-up visit (up to approximately 2 years 2 months) Safety analysis set included all randomized participants who had received at least 1 dose of study treatment (aducanumab or placebo). One participant in the placebo arm received drug. This participant was considered in Aducanumab group for safety analysis.
Infections and infestations Nasopharyngitis	7.6% 26/343 • From first dose of study drug up to last follow-up visit (up to approximately 2 years 2 months) Safety analysis set included all randomized participants who had received at least 1 dose of study treatment (aducanumab or placebo). One participant in the placebo arm received drug. This participant was considered in Aducanumab group for safety analysis.	6.2% 42/681 • From first dose of study drug up to last follow-up visit (up to approximately 2 years 2 months) Safety analysis set included all randomized participants who had received at least 1 dose of study treatment (aducanumab or placebo). One participant in the placebo arm received drug. This participant was considered in Aducanumab group for safety analysis.
Injury, poisoning and procedural complications Fall	9.3% 32/343 • From first dose of study drug up to last follow-up visit (up to approximately 2 years 2 months) Safety analysis set included all randomized participants who had received at least 1 dose of study treatment (aducanumab or placebo). One participant in the placebo arm received drug. This participant was considered in Aducanumab group for safety analysis.	8.1% 55/681 • From first dose of study drug up to last follow-up visit (up to approximately 2 years 2 months) Safety analysis set included all randomized participants who had received at least 1 dose of study treatment (aducanumab or placebo). One participant in the placebo arm received drug. This participant was considered in Aducanumab group for safety analysis.
Nervous system disorders Amyloid related imaging abnormality-microhaemorrhages and haemosiderin deposits	9.9% 34/343 • From first dose of study drug up to last follow-up visit (up to approximately 2 years 2 months) Safety analysis set included all randomized participants who had received at least 1 dose of study treatment (aducanumab or placebo). One participant in the placebo arm received drug. This participant was considered in Aducanumab group for safety analysis.	24.5% 167/681 • From first dose of study drug up to last follow-up visit (up to approximately 2 years 2 months) Safety analysis set included all randomized participants who had received at least 1 dose of study treatment (aducanumab or placebo). One participant in the placebo arm received drug. This participant was considered in Aducanumab group for safety analysis.
Nervous system disorders Amyloid related imaging abnormality-oedema/effusion	2.3% 8/343 • From first dose of study drug up to last follow-up visit (up to approximately 2 years 2 months) Safety analysis set included all randomized participants who had received at least 1 dose of study treatment (aducanumab or placebo). One participant in the placebo arm received drug. This participant was considered in Aducanumab group for safety analysis.	23.3% 159/681 • From first dose of study drug up to last follow-up visit (up to approximately 2 years 2 months) Safety analysis set included all randomized participants who had received at least 1 dose of study treatment (aducanumab or placebo). One participant in the placebo arm received drug. This participant was considered in Aducanumab group for safety analysis.
Nervous system disorders Dizziness	5.0% 17/343 • From first dose of study drug up to last follow-up visit (up to approximately 2 years 2 months) Safety analysis set included all randomized participants who had received at least 1 dose of study treatment (aducanumab or placebo). One participant in the placebo arm received drug. This participant was considered in Aducanumab group for safety analysis.	6.2% 42/681 • From first dose of study drug up to last follow-up visit (up to approximately 2 years 2 months) Safety analysis set included all randomized participants who had received at least 1 dose of study treatment (aducanumab or placebo). One participant in the placebo arm received drug. This participant was considered in Aducanumab group for safety analysis.
Nervous system disorders Headache	9.6% 33/343 • From first dose of study drug up to last follow-up visit (up to approximately 2 years 2 months) Safety analysis set included all randomized participants who had received at least 1 dose of study treatment (aducanumab or placebo). One participant in the placebo arm received drug. This participant was considered in Aducanumab group for safety analysis.	11.9% 81/681 • From first dose of study drug up to last follow-up visit (up to approximately 2 years 2 months) Safety analysis set included all randomized participants who had received at least 1 dose of study treatment (aducanumab or placebo). One participant in the placebo arm received drug. This participant was considered in Aducanumab group for safety analysis.
Nervous system disorders Superficial siderosis of central nervous system	1.5% 5/343 • From first dose of study drug up to last follow-up visit (up to approximately 2 years 2 months) Safety analysis set included all randomized participants who had received at least 1 dose of study treatment (aducanumab or placebo). One participant in the placebo arm received drug. This participant was considered in Aducanumab group for safety analysis.	10.1% 69/681 • From first dose of study drug up to last follow-up visit (up to approximately 2 years 2 months) Safety analysis set included all randomized participants who had received at least 1 dose of study treatment (aducanumab or placebo). One participant in the placebo arm received drug. This participant was considered in Aducanumab group for safety analysis.

Additional Information

US Biogen Clinical Trial Center

Biogen

Phone: 866-633-4636

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Our agreement is subject to confidentiality but generally, the PI can publish, for non-commercial purposes only, results and methods of the trial, but no other Sponsor's Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of the Sponsor's intellectual property contained in the proposed publication.
Publication restrictions are in place

Restriction type: OTHER