Trial Outcomes & Findings for A Study of Donanemab (LY3002813) Compared With Aducanumab in Participants With Early Symptomatic Alzheimer's Disease (TRAILBLAZER-ALZ 4) (NCT NCT05108922)

Last Updated: 2024-11-29

Results Overview

Amyloid deposition in the brain is one of the defining neuropathologic findings of Alzheimer's disease (AD). Amyloid PET scan assesses cerebral amyloid load using florbetapir tracer which is standardized into Centiloids for evaluation of AD. Florbetapir exhibits high affinity specific binding to amyloid plaques. Centiloid values on Centiloid scale is based on mean composite Standardized Uptake Value Ratio (SUVR) in cingulate, frontal, parietal and temporal cortexes using whole cerebellum as reference region. SUVR is ratio of tracer uptake in each of cingulate, frontal, parietal and temporal cortexes relative to cerebellum. Complete brain amyloid plaque clearance is a binary outcome and is defined as a Centiloid value \<24.1 from the florbetapir F18 PET scan.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

148 participants

Primary outcome timeframe

6 Months

Results posted on

2024-11-29

Participant Flow

Participant milestones

Participant milestones
Measure	Aducanumab Participants received aducanumab administered by intravenous (IV) infusion per US label (prescribing information/routine clinical practice).	Donanemab Participants received 700 milligram (mg) donanemab administered by IV infusion every 4 weeks (Q4W) for first three doses and then 1400 mg IV Q4W.
Overall Study STARTED	74	74
Overall Study Received at Least One Dose of Study Drug	69	71
Overall Study Intermediate Tau Analysis Set	28	27
Overall Study COMPLETED	55	58
Overall Study NOT COMPLETED	19	16

Reasons for withdrawal

Reasons for withdrawal
Measure	Aducanumab Participants received aducanumab administered by intravenous (IV) infusion per US label (prescribing information/routine clinical practice).	Donanemab Participants received 700 milligram (mg) donanemab administered by IV infusion every 4 weeks (Q4W) for first three doses and then 1400 mg IV Q4W.
Overall Study Adverse Event	2	3
Overall Study Lost to Follow-up	2	1
Overall Study Inadvertent enrollment	0	1
Overall Study Physician Decision	2	3
Overall Study Protocol deviation	1	0
Overall Study Screen failure	1	0
Overall Study Withdrawal by Subject	11	8

Baseline Characteristics

A Study of Donanemab (LY3002813) Compared With Aducanumab in Participants With Early Symptomatic Alzheimer's Disease (TRAILBLAZER-ALZ 4)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Aducanumab n=69 Participants Participants received aducanumab administered by IV infusion per US label (prescribing information/routine clinical practice).	Donanemab n=71 Participants Participants received 700 mg donanemab administered by IV infusion Q4W for first three doses and then 1400 mg IV Q4W.	Total n=140 Participants Total of all reporting groups
Age, Continuous	72.70 years STANDARD_DEVIATION 6.79 • n=5 Participants	74.10 years STANDARD_DEVIATION 6.87 • n=7 Participants	73.40 years STANDARD_DEVIATION 6.85 • n=5 Participants
Sex: Female, Male Female	42 Participants n=5 Participants	38 Participants n=7 Participants	80 Participants n=5 Participants
Sex: Female, Male Male	27 Participants n=5 Participants	33 Participants n=7 Participants	60 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	65 Participants n=5 Participants	67 Participants n=7 Participants	132 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants	0 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) White	61 Participants n=5 Participants	71 Participants n=7 Participants	132 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	69 Participants n=5 Participants	71 Participants n=7 Participants	140 Participants n=5 Participants

PRIMARY outcome

Timeframe: 6 Months

Population: All randomized participants who received at least one dose of study drug to donanemab or aducanumab with a baseline and at least one postbaseline Florbetapir F18 PET scan data at the primary outcome (6-month) database lock.

Outcome measures

Outcome measures
Measure	Aducanumab n=64 Participants Participants received aducanumab administered by IV infusion per US label (prescribing information/routine clinical practice).	Donanemab n=66 Participants Participants received 700 mg donanemab administered by IV infusion Q4W for first three doses and then 1400 mg IV Q4W.
Percentage of Participants Who Reach Complete Amyloid Plaque Clearance on Florbetapir F18 Positron Emission Tomography (PET) Scan (Superiority) on Donanemab Versus Aducanumab	1.6 Percentage of participants Interval 0.0 to 4.6	37.9 Percentage of participants Interval 26.2 to 49.6

PRIMARY outcome

Timeframe: 6 Months

Complete brain amyloid plaque clearance is a binary outcome and is defined as a Centiloid value \<24.1 from the florbetapir F18 PET scan.

Outcome measures

Outcome measures
Measure	Aducanumab n=26 Participants Participants received aducanumab administered by IV infusion per US label (prescribing information/routine clinical practice).	Donanemab n=26 Participants Participants received 700 mg donanemab administered by IV infusion Q4W for first three doses and then 1400 mg IV Q4W.
Percentage of Participants Who Reach Complete Amyloid Plaque Clearance on Florbetapir F18 PET Scan in the Low/Medium (Intermediate) Subpopulation (Superiority) on Donanemab Versus Aducanumab	3.8 Percentage of participants Interval 0.0 to 11.2	38.5 Percentage of participants Interval 19.8 to 57.2

SECONDARY outcome

Timeframe: Baseline, 6 Months

Florbetapir PET imaging was used as a quantitative amyloid biomarker. Quantitative amyloid burden was first formalized as the average Standardized Uptake Value Ratio (SUVR) in six predetermined cortical areas of the brain relative to the cerebellum as a reference region. Larger SUVR reflects the larger cortical amyloid burden relative to cerebellum. SUVR values were further calibrated to a Centiloid (CL) scale. The Centiloid scale anchor points are 0 and 100, where 0 represents a high-certainty amyloid negative scan and 100 represents the amount of global amyloid deposition found in a typical AD scan. A negative change indicates an improvement from baseline.

Outcome measures

Outcome measures
Measure	Aducanumab n=64 Participants Participants received aducanumab administered by IV infusion per US label (prescribing information/routine clinical practice).	Donanemab n=66 Participants Participants received 700 mg donanemab administered by IV infusion Q4W for first three doses and then 1400 mg IV Q4W.
Mean Absolute Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) on Donanemab Versus Aducanumab	-16.413 Centiloids Standard Error 3.7685	-62.104 Centiloids Standard Error 3.6898

SECONDARY outcome

Timeframe: Baseline, 6 Months

Outcome measures

Outcome measures
Measure	Aducanumab n=64 Participants Participants received aducanumab administered by IV infusion per US label (prescribing information/routine clinical practice).	Donanemab n=66 Participants Participants received 700 mg donanemab administered by IV infusion Q4W for first three doses and then 1400 mg IV Q4W.
Mean Percent Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) Donanemab Versus Aducanumab	-16.956 Percent change Standard Error 4.0253	-65.169 Percent change Standard Error 3.9412

SECONDARY outcome

Timeframe: Baseline, 6 Months

Outcome measures

Outcome measures
Measure	Aducanumab n=26 Participants Participants received aducanumab administered by IV infusion per US label (prescribing information/routine clinical practice).	Donanemab n=26 Participants Participants received 700 mg donanemab administered by IV infusion Q4W for first three doses and then 1400 mg IV Q4W.
Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan in the Low/Medium (Intermediate) Tau Subpopulation (Superiority) on Donanemab Versus Aducanumab	-23.824 Centiloids Standard Error 7.7028	-64.076 Centiloids Standard Error 7.3359

SECONDARY outcome

Timeframe: Baseline, 12 Months

Outcome measures

Outcome measures
Measure	Aducanumab n=65 Participants Participants received aducanumab administered by IV infusion per US label (prescribing information/routine clinical practice).	Donanemab n=67 Participants Participants received 700 mg donanemab administered by IV infusion Q4W for first three doses and then 1400 mg IV Q4W.
Mean Absolute Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) on Donanemab Versus Aducanumab	-56.06 Centiloids Standard Error 2.977	-80.03 Centiloids Standard Error 2.973

SECONDARY outcome

Timeframe: Baseline, 12 Months

Outcome measures

Outcome measures
Measure	Aducanumab n=65 Participants Participants received aducanumab administered by IV infusion per US label (prescribing information/routine clinical practice).	Donanemab n=67 Participants Participants received 700 mg donanemab administered by IV infusion Q4W for first three doses and then 1400 mg IV Q4W.
Mean Percent Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) Donanemab Versus Aducanumab	-56.97 Percent change Standard Error 3.081	-82.79 Percent change Standard Error 3.077

SECONDARY outcome

Timeframe: 12 Months

Outcome measures

Outcome measures
Measure	Aducanumab n=65 Participants Participants received aducanumab administered by IV infusion per US label (prescribing information/routine clinical practice).	Donanemab n=67 Participants Participants received 700 mg donanemab administered by IV infusion Q4W for first three doses and then 1400 mg IV Q4W.
Percentage of Participants Who Reach Complete Amyloid Plaque Clearance on Florbetapir F18 Positron Emission Tomography (PET) Scan (Superiority) on Donanemab Versus Aducanumab	24.59 Percentage of participants	70.00 Percentage of participants

SECONDARY outcome

Timeframe: 12 Months

Outcome measures

Outcome measures
Measure	Aducanumab n=27 Participants Participants received aducanumab administered by IV infusion per US label (prescribing information/routine clinical practice).	Donanemab n=26 Participants Participants received 700 mg donanemab administered by IV infusion Q4W for first three doses and then 1400 mg IV Q4W.
Percentage of Participants Who Reach Complete Amyloid Plaque Clearance on Florbetapir F18 PET Scan in the Low/Medium (Intermediate) Subpopulation (Superiority) on Donanemab Versus Aducanumab	18.52 percentage of participants	76.00 percentage of participants

SECONDARY outcome

Timeframe: Baseline, 12 Months

Outcome measures

Outcome measures
Measure	Aducanumab n=27 Participants Participants received aducanumab administered by IV infusion per US label (prescribing information/routine clinical practice).	Donanemab n=26 Participants Participants received 700 mg donanemab administered by IV infusion Q4W for first three doses and then 1400 mg IV Q4W.
Mean Absolute Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan in the Low/Medium (Intermediate) Tau Subpopulation (Superiority) on Donanemab Versus Aducanumab	-57.77 Centiloids Standard Error 4.419	-84.53 Centiloids Standard Error 4.565

SECONDARY outcome

Timeframe: Baseline, 6 Months and 12 Months

Outcome measures

Outcome measures
Measure	Aducanumab n=65 Participants Participants received aducanumab administered by IV infusion per US label (prescribing information/routine clinical practice).	Donanemab n=67 Participants Participants received 700 mg donanemab administered by IV infusion Q4W for first three doses and then 1400 mg IV Q4W.
Mean Absolute Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) on Donanemab 6 Months Versus Aducanumab 12 Months	-56.056 Centiloids Standard Error 2.9768	-63.987 Centiloids Standard Error 2.8142

SECONDARY outcome

Timeframe: Baseline, 6 Months and 12 Months

Outcome measures

Outcome measures
Measure	Aducanumab n=65 Participants Participants received aducanumab administered by IV infusion per US label (prescribing information/routine clinical practice).	Donanemab n=67 Participants Participants received 700 mg donanemab administered by IV infusion Q4W for first three doses and then 1400 mg IV Q4W.
Mean Absolute Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Non-inferiority) on Donanemab 6 Months Versus Aducanumab 12 Months	-56.056 Centiloids Standard Error 2.9768	-63.987 Centiloids Standard Error 2.8142

SECONDARY outcome

Timeframe: Baseline, 18 Months

Outcome measures

Outcome measures
Measure	Aducanumab n=65 Participants Participants received aducanumab administered by IV infusion per US label (prescribing information/routine clinical practice).	Donanemab n=67 Participants Participants received 700 mg donanemab administered by IV infusion Q4W for first three doses and then 1400 mg IV Q4W.
Mean Absolute Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) on Donanemab Versus Aducanumab	-72.18 Centiloids Standard Error 2.883	-84.22 Centiloids Standard Error 2.905

SECONDARY outcome

Timeframe: 18 Months

Time to reach complete amyloid plaque clearance at 18 months was evaluated.

Outcome measures

Outcome measures
Measure	Aducanumab n=65 Participants Participants received aducanumab administered by IV infusion per US label (prescribing information/routine clinical practice).	Donanemab n=67 Participants Participants received 700 mg donanemab administered by IV infusion Q4W for first three doses and then 1400 mg IV Q4W.
Time to Reach Complete Amyloid Plaque Clearance on Donanemab Versus Aducanumab	568.00 days Interval 542.0 to Upper limit of 95% confidence interval was not calculated as there were not enough events.	359.00 days Interval 343.0 to 377.0

SECONDARY outcome

Timeframe: Baseline, 18 Months

Outcome measures

Outcome measures
Measure	Aducanumab n=65 Participants Participants received aducanumab administered by IV infusion per US label (prescribing information/routine clinical practice).	Donanemab n=67 Participants Participants received 700 mg donanemab administered by IV infusion Q4W for first three doses and then 1400 mg IV Q4W.
Mean Percent Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Superiority) Donanemab Versus Aducanumab	-72.84 percent change Standard Error 3.011	-86.29 percent change Standard Error 3.030

SECONDARY outcome

Timeframe: 18 Months

Outcome measures

Outcome measures
Measure	Aducanumab n=65 Participants Participants received aducanumab administered by IV infusion per US label (prescribing information/routine clinical practice).	Donanemab n=67 Participants Participants received 700 mg donanemab administered by IV infusion Q4W for first three doses and then 1400 mg IV Q4W.
Percentage of Participants Who Reach Complete Amyloid Plaque Clearance on Florbetapir F18 Positron Emission Tomography (PET) Scan (Superiority) on Donanemab Versus Aducanumab	43.10 percentage of participants	76.79 percentage of participants

SECONDARY outcome

Timeframe: 18 Months

Complete brain amyloid plaque clearance is a binary outcome and is defined as a Centiloid value \<24.1 from the florbetapir F18 PET scan.

Outcome measures

Outcome measures
Measure	Aducanumab n=27 Participants Participants received aducanumab administered by IV infusion per US label (prescribing information/routine clinical practice).	Donanemab n=26 Participants Participants received 700 mg donanemab administered by IV infusion Q4W for first three doses and then 1400 mg IV Q4W.
Percentage of Participants Who Reach Complete Amyloid Plaque Clearance on Florbetapir F18 PET Scan in the Low/Medium (Intermediate) Subpopulation (Superiority) on Donanemab Versus Aducanumab	43.48 percentage of participants	72.00 percentage of participants

SECONDARY outcome

Timeframe: Baseline, 18 Months

Outcome measures

Outcome measures
Measure	Aducanumab n=27 Participants Participants received aducanumab administered by IV infusion per US label (prescribing information/routine clinical practice).	Donanemab n=26 Participants Participants received 700 mg donanemab administered by IV infusion Q4W for first three doses and then 1400 mg IV Q4W.
Mean Absolute Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan in the Low/Medium (Intermediate) Tau Subpopulation (Superiority) on Donanemab Versus Aducanumab	-72.24 Centiloids Standard Error 4.374	-86.57 Centiloids Standard Error 4.408

SECONDARY outcome

Timeframe: Baseline, 6 Months and 18 Months

Outcome measures

Outcome measures
Measure	Aducanumab n=65 Participants Participants received aducanumab administered by IV infusion per US label (prescribing information/routine clinical practice).	Donanemab n=67 Participants Participants received 700 mg donanemab administered by IV infusion Q4W for first three doses and then 1400 mg IV Q4W.
Mean Absolute Change From Baseline in Brain Amyloid Plaque on Florbetapir F18 PET Scan (Non-inferiority) on Donanemab 6 Months Versus Aducanumab 18 Months	-72.178 Centiloids Standard Error 2.8834	-64.347 Centiloids Standard Error 2.8645

Adverse Events

Aducanumab

Serious events: 8 serious events

Other events: 59 other events

Deaths: 0 deaths

Donanemab

Serious events: 13 serious events

Other events: 58 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Aducanumab n=69 participants at risk Participants received aducanumab administered by IV infusion per US label (prescribing information/routine clinical practice).	Donanemab n=71 participants at risk Participants received 700 mg donanemab administered by IV infusion Q4W for first three doses and then 1400 mg IV Q4W.
Blood and lymphatic system disorders Anaemia	1.4% 1/69 • Number of events 1 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.	0.00% 0/71 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.
Cardiac disorders Atrioventricular block second degree	1.4% 1/69 • Number of events 1 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.	0.00% 0/71 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.
Cardiac disorders Bradycardia	1.4% 1/69 • Number of events 1 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.	0.00% 0/71 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.
Cardiac disorders Myocardial ischaemia	0.00% 0/69 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.	1.4% 1/71 • Number of events 1 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.
Cardiac disorders Pericardial effusion	0.00% 0/69 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.	1.4% 1/71 • Number of events 1 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.
Gastrointestinal disorders Nausea	0.00% 0/69 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.	1.4% 1/71 • Number of events 1 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.
Gastrointestinal disorders Vomiting	0.00% 0/69 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.	1.4% 1/71 • Number of events 1 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.
General disorders Chest pain	2.9% 2/69 • Number of events 2 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.	0.00% 0/71 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.
General disorders Gait disturbance	1.4% 1/69 • Number of events 1 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.	0.00% 0/71 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.
General disorders Non-cardiac chest pain	1.4% 1/69 • Number of events 1 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.	0.00% 0/71 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.
Hepatobiliary disorders Cholecystitis	1.4% 1/69 • Number of events 1 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.	0.00% 0/71 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.
Infections and infestations Covid-19	1.4% 1/69 • Number of events 1 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.	2.8% 2/71 • Number of events 2 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.
Infections and infestations Diverticulitis	0.00% 0/69 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.	1.4% 1/71 • Number of events 1 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.
Infections and infestations Pneumonia	0.00% 0/69 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.	4.2% 3/71 • Number of events 3 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.
Infections and infestations Sepsis	0.00% 0/69 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.	1.4% 1/71 • Number of events 1 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.
Injury, poisoning and procedural complications Cartilage injury	0.00% 0/69 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.	1.4% 1/71 • Number of events 1 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.
Injury, poisoning and procedural complications Fall	0.00% 0/69 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.	1.4% 1/71 • Number of events 2 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.
Injury, poisoning and procedural complications Rib fracture	0.00% 0/69 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.	1.4% 1/71 • Number of events 1 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.
Metabolism and nutrition disorders Hypervolaemia	1.4% 1/69 • Number of events 1 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.	0.00% 0/71 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Leukaemia	0.00% 0/69 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.	1.4% 1/71 • Number of events 1 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.
Nervous system disorders Amyloid related imaging abnormality-oedema/effusion	2.9% 2/69 • Number of events 2 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.	0.00% 0/71 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.
Nervous system disorders Brain oedema	0.00% 0/69 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.	1.4% 1/71 • Number of events 1 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.
Nervous system disorders Dizziness	0.00% 0/69 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.	1.4% 1/71 • Number of events 1 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.
Nervous system disorders Syncope	1.4% 1/69 • Number of events 1 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.	0.00% 0/71 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.
Nervous system disorders Transient ischaemic attack	1.4% 1/69 • Number of events 1 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.	0.00% 0/71 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/69 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.	1.4% 1/71 • Number of events 1 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Pneumomediastinum	0.00% 0/69 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.	1.4% 1/71 • Number of events 1 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/69 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.	1.4% 1/71 • Number of events 1 • Baseline Up to Week 76 All randomized participants who received at least one dose of study drug to donanemab or aducanumab. Gender specific events only occurring in male or female participants have had the number of participants at Risk adjusted accordingly.