Trial Outcomes & Findings for A Study of Donanemab (LY3002813) in Participants With Early Alzheimer's Disease (TRAILBLAZER-ALZ 2) (NCT NCT04437511)

Last Updated: 2025-08-29

Results Overview

Integrated Alzheimer's Disease Rating Scale is used to assess whether donanemab slows down the clinical decline associated with AD compared with placebo. iADRS is an integrated assessment of cognition and daily function comprised of items from the ADAS-Cog13 and the Alzheimer's disease cooperative study-instrumental activities of daily living scale (ADCS-iADL). The scale ranges from 0 to 144, where lower scores indicate worse performance and higher score indicates better performance. Least Squares (LS) Mean value was adjusted for basis expansion terms (two terms), basis expansion term-by-treatment interaction, and covariates for age at baseline, pooled investigator, baseline tau level, and baseline acetylcholinesterase inhibitor (AchI)/Memantine use.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE3

Target enrollment

1736 participants

Primary outcome timeframe

Baseline, Week 76

Results posted on

2025-08-29

Participant Flow

Participant milestones

Participant milestones
Measure	Donanemab Participants received 700 milligram (mg) Donanemab every 4 weeks (Q4W) x 3 doses, then 1400 mg Q4W given intravenously (IV) for up to 72 weeks	Placebo Participants received placebo given IV.
Overall Study STARTED	860	876
Overall Study Received at Least One Dose of Drug (Safety Population)	853	874
Overall Study COMPLETED	622	698
Overall Study NOT COMPLETED	238	178

Reasons for withdrawal

Reasons for withdrawal
Measure	Donanemab Participants received 700 milligram (mg) Donanemab every 4 weeks (Q4W) x 3 doses, then 1400 mg Q4W given intravenously (IV) for up to 72 weeks	Placebo Participants received placebo given IV.
Overall Study Adverse Event	50	21
Overall Study Death	15	10
Overall Study Lost to Follow-up	11	11
Overall Study Physician Decision	19	10
Overall Study Progressive Disease	4	7
Overall Study Withdrawal by Subject	111	94
Overall Study Withdrawal due to Caregiver Circumstances	21	20
Overall Study Continuing Study	7	5

Baseline Characteristics

Safety Population: All randomized participants who received at least one dose of study drug.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Donanemab n=860 Participants Participants received 700 mg Donanemab Q4W x 3 doses, then 1400 mg Q4W given IV for up to 72 weeks.	Placebo n=876 Participants Participants received placebo given IV.	Total n=1736 Participants Total of all reporting groups
Age, Continuous	72.98 years STANDARD_DEVIATION 6.16 • n=860 Participants	73.04 years STANDARD_DEVIATION 6.20 • n=876 Participants	73.01 years STANDARD_DEVIATION 6.18 • n=1736 Participants
Sex/Gender, Customized Female	488 participants n=853 Participants • Safety Population: All randomized participants who received at least one dose of study drug.	501 participants n=874 Participants • Safety Population: All randomized participants who received at least one dose of study drug.	989 participants n=1727 Participants • Safety Population: All randomized participants who received at least one dose of study drug.
Sex/Gender, Customized Male	365 participants n=853 Participants • Safety Population: All randomized participants who received at least one dose of study drug.	373 participants n=874 Participants • Safety Population: All randomized participants who received at least one dose of study drug.	738 participants n=1727 Participants • Safety Population: All randomized participants who received at least one dose of study drug.
Sex: Female, Male Female	493 Participants n=860 Participants	503 Participants n=876 Participants	996 Participants n=1736 Participants
Sex: Female, Male Male	367 Participants n=860 Participants	373 Participants n=876 Participants	740 Participants n=1736 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	35 Participants n=860 Participants	36 Participants n=876 Participants	71 Participants n=1736 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	583 Participants n=860 Participants	594 Participants n=876 Participants	1177 Participants n=1736 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	242 Participants n=860 Participants	246 Participants n=876 Participants	488 Participants n=1736 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=860 Participants	0 Participants n=876 Participants	2 Participants n=1736 Participants
Race (NIH/OMB) Asian	57 Participants n=860 Participants	47 Participants n=876 Participants	104 Participants n=1736 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=860 Participants	0 Participants n=876 Participants	0 Participants n=1736 Participants
Race (NIH/OMB) Black or African American	19 Participants n=860 Participants	21 Participants n=876 Participants	40 Participants n=1736 Participants
Race (NIH/OMB) White	781 Participants n=860 Participants	807 Participants n=876 Participants	1588 Participants n=1736 Participants
Race (NIH/OMB) More than one race	0 Participants n=860 Participants	1 Participants n=876 Participants	1 Participants n=1736 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=860 Participants	0 Participants n=876 Participants	1 Participants n=1736 Participants
Region of Enrollment Australia	13 Participants n=860 Participants	4 Participants n=876 Participants	17 Participants n=1736 Participants
Region of Enrollment Canada	64 Participants n=860 Participants	73 Participants n=876 Participants	137 Participants n=1736 Participants
Region of Enrollment Czechia	12 Participants n=860 Participants	10 Participants n=876 Participants	22 Participants n=1736 Participants
Region of Enrollment Japan	45 Participants n=860 Participants	43 Participants n=876 Participants	88 Participants n=1736 Participants
Region of Enrollment Netherlands	13 Participants n=860 Participants	9 Participants n=876 Participants	22 Participants n=1736 Participants
Region of Enrollment Poland	77 Participants n=860 Participants	82 Participants n=876 Participants	159 Participants n=1736 Participants
Region of Enrollment United Kingdom	16 Participants n=860 Participants	23 Participants n=876 Participants	39 Participants n=1736 Participants
Region of Enrollment United States	620 Participants n=860 Participants	632 Participants n=876 Participants	1252 Participants n=1736 Participants
Integrated Alzheimer's Disease Rating Scale (iADRS)	104.10 Score on a scale STANDARD_DEVIATION 14.30 • n=860 Participants	103.56 Score on a scale STANDARD_DEVIATION 14.02 • n=876 Participants	103.83 Score on a scale STANDARD_DEVIATION 14.16 • n=1736 Participants
Screening Tau Category Intermediate (Low-medium)	588 Participants n=859 Participants • All randomized participants (pts) who have only evaluable Screening Tau category data.Intermediate tau (Low-medium):All pts with baseline composite tau PET standardized uptake value ratio (SUVr) \<= 1.46 and a topographic deposition pattern consistent with advanced AD (AD++) or 1.10 \<= SUVr \<= 1.46 and a topographic deposition pattern consistent with moderate AD (AD+).High tau:All pts with SUVr \>1.46 and topographic deposition pattern consistent with either moderate (AD+) or advanced AD (AD++).	594 Participants n=875 Participants • All randomized participants (pts) who have only evaluable Screening Tau category data.Intermediate tau (Low-medium):All pts with baseline composite tau PET standardized uptake value ratio (SUVr) \<= 1.46 and a topographic deposition pattern consistent with advanced AD (AD++) or 1.10 \<= SUVr \<= 1.46 and a topographic deposition pattern consistent with moderate AD (AD+).High tau:All pts with SUVr \>1.46 and topographic deposition pattern consistent with either moderate (AD+) or advanced AD (AD++).	1182 Participants n=1734 Participants • All randomized participants (pts) who have only evaluable Screening Tau category data.Intermediate tau (Low-medium):All pts with baseline composite tau PET standardized uptake value ratio (SUVr) \<= 1.46 and a topographic deposition pattern consistent with advanced AD (AD++) or 1.10 \<= SUVr \<= 1.46 and a topographic deposition pattern consistent with moderate AD (AD+).High tau:All pts with SUVr \>1.46 and topographic deposition pattern consistent with either moderate (AD+) or advanced AD (AD++).
Screening Tau Category High	271 Participants n=859 Participants • All randomized participants (pts) who have only evaluable Screening Tau category data.Intermediate tau (Low-medium):All pts with baseline composite tau PET standardized uptake value ratio (SUVr) \<= 1.46 and a topographic deposition pattern consistent with advanced AD (AD++) or 1.10 \<= SUVr \<= 1.46 and a topographic deposition pattern consistent with moderate AD (AD+).High tau:All pts with SUVr \>1.46 and topographic deposition pattern consistent with either moderate (AD+) or advanced AD (AD++).	281 Participants n=875 Participants • All randomized participants (pts) who have only evaluable Screening Tau category data.Intermediate tau (Low-medium):All pts with baseline composite tau PET standardized uptake value ratio (SUVr) \<= 1.46 and a topographic deposition pattern consistent with advanced AD (AD++) or 1.10 \<= SUVr \<= 1.46 and a topographic deposition pattern consistent with moderate AD (AD+).High tau:All pts with SUVr \>1.46 and topographic deposition pattern consistent with either moderate (AD+) or advanced AD (AD++).	552 Participants n=1734 Participants • All randomized participants (pts) who have only evaluable Screening Tau category data.Intermediate tau (Low-medium):All pts with baseline composite tau PET standardized uptake value ratio (SUVr) \<= 1.46 and a topographic deposition pattern consistent with advanced AD (AD++) or 1.10 \<= SUVr \<= 1.46 and a topographic deposition pattern consistent with moderate AD (AD+).High tau:All pts with SUVr \>1.46 and topographic deposition pattern consistent with either moderate (AD+) or advanced AD (AD++).

PRIMARY outcome

Timeframe: Baseline, Week 76

Population: All randomized participants with a baseline and at least one postbaseline iADRS data point.

Outcome measures

Outcome measures
Measure	Donanemab n=775 Participants Participants received 700 mg Donanemab Q4W x 3 doses, then 1400 mg Q4W given IV for up to 72 weeks	Placebo n=824 Participants Participants received placebo given IV.
Change From Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS) (Overall Population)	-10.19 score on a scale Standard Error 0.53	-13.11 score on a scale Standard Error 0.50

PRIMARY outcome

Timeframe: Baseline, Week 76

Population: All randomized participants with baseline Intermediate Tau level and with baseline and at least one postbaseline iADRS data point.

Integrated Alzheimer's Disease Rating Scale is used to assess whether donanemab slows down the clinical decline associated with AD compared with placebo. iADRS is an integrated assessment of cognition and daily function comprised of items from the Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog13) and the Alzheimer's disease cooperative study-instrumental activities of daily living scale (ADCS-iADL). The scale ranges from 0 to 144, where lower scores indicate worse performance and higher score indicates better performance. LS Mean value was adjusted for basis expansion terms (two terms), basis expansion term-by-treatment interaction, and covariates for age at baseline, pooled investigator, and baseline AchI/Memantine use.

Outcome measures

Outcome measures
Measure	Donanemab n=533 Participants Participants received 700 mg Donanemab Q4W x 3 doses, then 1400 mg Q4W given IV for up to 72 weeks	Placebo n=560 Participants Participants received placebo given IV.
Change From Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS) (Intermediate (Low-medium) Tau Population)	-6.02 score on a scale Standard Error 0.50	-9.27 score on a scale Standard Error 0.49

SECONDARY outcome

Timeframe: Baseline, Week 76

Population: All randomized participants with a baseline and at least one postbaseline MMSE data point.

MMSE is an instrument used to assess cognitive function (orientation, memory, attention, ability to name objects, follow verbal/written commands, write a sentence, and copy figures). Total score ranges from 0 to 30; lower score indicates greater disease severity. LS Mean value was adjusted for basis expansion terms (two terms), basis expansion term-by-treatment interaction, and covariates for age at baseline, pooled investigator, baseline tau level, and baseline AchI/Memantine use.

Outcome measures

Outcome measures
Measure	Donanemab n=796 Participants Participants received 700 mg Donanemab Q4W x 3 doses, then 1400 mg Q4W given IV for up to 72 weeks	Placebo n=841 Participants Participants received placebo given IV.
Change From Baseline on the Mini Mental State Examination (MMSE) Score (Overall Population)	-2.47 score on a scale Standard Error 0.14	-2.94 score on a scale Standard Error 0.13

SECONDARY outcome

Timeframe: Baseline, Week 76

Population: All randomized participants with baseline Intermediate Tau level and with baseline and at least one postbaseline MMSE data point.

Outcome measures

Outcome measures
Measure	Donanemab n=549 Participants Participants received 700 mg Donanemab Q4W x 3 doses, then 1400 mg Q4W given IV for up to 72 weeks	Placebo n=573 Participants Participants received placebo given IV.
Change From Baseline on the Mini Mental State Examination (MMSE) Score (Intermediate (Low-medium) Tau Population)	-1.61 score on a scale Standard Error 0.14	-2.09 score on a scale Standard Error 0.14

SECONDARY outcome

Timeframe: Baseline, Week 76

Population: All randomized participants with a baseline and at least one postbaseline ADAS-Cog13 data point.

The ADAS-Cog13 is a rater administered instrument that was designed to assess the severity of the dysfunction in the cognitive and noncognitive behaviors characteristic of persons with AD. The cognitive subscale of the ADAS-Cog13 consists of 13 items assessing areas of cognitive function most typically impaired in AD: orientation, verbal memory, language, praxis, delayed free recall, digit cancellation. The ADAS-Cog13 scale ranges from 0 to 85. Higher scores indicate greater disease severity. LS Mean value was adjusted for basis expansion terms (two terms), basis expansion term-by-treatment interaction, and covariates for age at baseline, pooled investigator, baseline tau level, and baseline AchI/Memantine use.

Outcome measures

Outcome measures
Measure	Donanemab n=797 Participants Participants received 700 mg Donanemab Q4W x 3 doses, then 1400 mg Q4W given IV for up to 72 weeks	Placebo n=841 Participants Participants received placebo given IV.
Change From Baseline on the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) (Overall Population)	5.46 score on a scale Standard Error 0.28	6.79 score on a scale Standard Error 0.27

SECONDARY outcome

Timeframe: Baseline, Week 76

Population: All randomized participants with baseline Intermediate Tau level and with baseline and at least one postbaseline ADAS-Cog13 data point.

The ADAS is a rater administered instrument that was designed to assess the severity of the dysfunction in the cognitive and noncognitive behaviors characteristic of persons with AD. The cognitive subscale of the ADAS-cog consists of 13 items assessing areas of cognitive function most typically impaired in AD: orientation, verbal memory, language, praxis, delayed free recall, digit cancellation. The ADAS-Cog13 scale ranges from 0 to 85. Higher scores indicate greater disease severity. LS Mean value was adjusted for basis expansion terms (two terms), basis expansion term-by-treatment interaction, and covariates for age at baseline, pooled investigator, and baseline AchI/Memantine use.

Outcome measures

Outcome measures
Measure	Donanemab n=550 Participants Participants received 700 mg Donanemab Q4W x 3 doses, then 1400 mg Q4W given IV for up to 72 weeks	Placebo n=570 Participants Participants received placebo given IV.
Change From Baseline on the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) (Intermediate (Low-medium) Tau Population)	3.17 score on a scale Standard Error 0.27	4.69 score on a scale Standard Error 0.26

SECONDARY outcome

Timeframe: Baseline, Week 76

Population: All randomized participants with a baseline and at least one postbaseline CDR-SB data point.

CDR-SB is a semi-structured interview of participants and their caregivers. Participant's cognitive status is rated across 6 domains of functioning, including memory, orientation, judgment/problem solving, community affairs, home/hobbies, and personal care. Severity score assigned for each of 6 domains; Total score (SB) ranges from 0 to 18. Higher scores indicate greater disease severity. LS Mean value was adjusted for treatment, visit, treatment-by-visit interaction, and covariates for baseline score, baseline score-by-visit interaction, age at baseline, baseline tau category, pooled investigator, and baseline AchI/Memantine use.

Outcome measures

Outcome measures
Measure	Donanemab n=794 Participants Participants received 700 mg Donanemab Q4W x 3 doses, then 1400 mg Q4W given IV for up to 72 weeks	Placebo n=838 Participants Participants received placebo given IV.
Change From Baseline on the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) (Overall Population)	1.72 score on a scale Standard Error 0.096	2.42 score on a scale Standard Error 0.092

SECONDARY outcome

Timeframe: Baseline, Week 76

Population: All randomized participants with baseline Intermediate Tau level and with baseline and at least one postbaseline CDR-SB data point.

CDR-SB is a semi-structured interview of participants and their caregivers. Participant's cognitive status is rated across 6 domains of functioning, including memory, orientation, judgment/problem solving, community affairs, home/hobbies, and personal care. Severity score assigned for each of 6 domains; Total score (SB) ranges from 0 to 18. Higher scores indicate greater disease severity. LS Mean value was adjusted for treatment, visit, treatment-by-visit interaction, and covariates for baseline score, baseline score-by-visit interaction, age at baseline, pooled investigator, and baseline AchI/Memantine use.

Outcome measures

Outcome measures
Measure	Donanemab n=546 Participants Participants received 700 mg Donanemab Q4W x 3 doses, then 1400 mg Q4W given IV for up to 72 weeks	Placebo n=569 Participants Participants received placebo given IV.
Change From Baseline on the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) (Intermediate (Low-medium) Tau Population)	1.20 score on a scale Standard Error 0.105	1.88 score on a scale Standard Error 0.102

SECONDARY outcome

Timeframe: Baseline, Week 76

Population: All randomized participants with a baseline and at least one postbaseline ADCS-iADL data point.

The ADCS-ADL is a 23-item inventory developed as a rater-administered questionnaire answered by the participant's caregiver. The ADCS-ADL measures both basic and instrumental activities (instrumental activity items 6a, 7-23) of daily living by participants. The range for the ADCS-iADL is 0-59 with higher scores reflecting better performance. LS Mean value was adjusted for basis expansion terms (two terms), basis expansion term-by-treatment interaction, and covariates for age at baseline, pooled investigator, baseline tau level, and baseline AchI/Memantine use.

Outcome measures

Outcome measures
Measure	Donanemab n=780 Participants Participants received 700 mg Donanemab Q4W x 3 doses, then 1400 mg Q4W given IV for up to 72 weeks	Placebo n=826 Participants Participants received placebo given IV.
Change From Baseline on the Alzheimer's Disease Cooperative Study - Instrumental Activities of Daily Living (ADCS-iADL) Score (Overall Population)	-4.42 score on a scale Standard Error 0.32	-6.13 score on a scale Standard Error 0.30

SECONDARY outcome

Timeframe: Baseline, Week 76

Population: All randomized participants with a baseline Intermediate Tau level and with baseline and at least one postbaseline ADCS-iADL data point.

Outcome measures

Outcome measures
Measure	Donanemab n=535 Participants Participants received 700 mg Donanemab Q4W x 3 doses, then 1400 mg Q4W given IV for up to 72 weeks	Placebo n=562 Participants Participants received placebo given IV.
Change From Baseline on the Alzheimer's Disease Cooperative Study - Instrumental Activities of Daily Living (ADCS-iADL) Score (Intermediate (Low-medium) Tau Population)	-2.76 score on a scale Standard Error 0.34	-4.59 score on a scale Standard Error 0.32

SECONDARY outcome

Timeframe: Baseline, Week 76

Population: All randomized participants with a baseline and at least one postbaseline amyloid PET scan data point.

Amyloid PET scans at baseline and at 76 weeks after the first treatment were used to quantitatively estimate change in amyloid plaques. Quantitative amyloid burden was first formalized as the average Standardized Uptake Value Ratio (SUVR) in six predetermined cortical brain regions 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. LS Mean value was adjusted for treatment, visit, treatment-by-visit interaction, and covariates for baseline score, baseline score-by-visit interaction, baseline tau category, and age at baseline.

Outcome measures

Outcome measures
Measure	Donanemab n=765 Participants Participants received 700 mg Donanemab Q4W x 3 doses, then 1400 mg Q4W given IV for up to 72 weeks	Placebo n=812 Participants Participants received placebo given IV.
Change From Baseline in Brain Amyloid Plaque Deposition as Measured by Amyloid Positron Emission Tomography (PET) Scan	-87.03 centiloids Standard Error 0.950	-0.67 centiloids Standard Error 0.909

SECONDARY outcome

Timeframe: Baseline, Week 76

Population: All randomized participants with a baseline and post-baseline tau PET scan.

Flortaucipir PET imaging was used as a quantitative tau biomarker. Tau PET scans at baseline and at 76 weeks after the first treatment were used to quantitatively estimate change in aggregated tau neurofibrillary tangles (NFTs). Quantitative tau burden was formalized using Standardized Uptake Value Ratio (SUVR) in frontal lobe relative to the cerebellum gray as a reference region. Larger SUVR reflects larger tau burden in the frontal lobe relative to cerebellum gray. LS Mean value was adjusted for baseline score, screening tau category, age and treatment (Type III sum of squares).

Outcome measures

Outcome measures
Measure	Donanemab n=578 Participants Participants received 700 mg Donanemab Q4W x 3 doses, then 1400 mg Q4W given IV for up to 72 weeks	Placebo n=654 Participants Participants received placebo given IV.
Change From Baseline in Brain Tau Deposition as Measured by Flortaucipir F18 PET Scan	0.0401 standardized uptake value ratio (SUVR) Standard Error 0.00398	0.0442 standardized uptake value ratio (SUVR) Standard Error 0.00374

SECONDARY outcome

Timeframe: Baseline, Week 76

Population: All randomized participants with a baseline and at least one postbaseline vMRI data point.

MRI scans at baseline and at 76 weeks after the first treatment were used to quantitatively estimate change in brain volume. Volumetric MRI parameters were measured in bilateral hippocampus, bilateral whole brain, and bilateral ventricles. LS Mean value was adjusted for treatment, visit, treatment-by-visit interaction, and covariates for baseline score, baseline tau category, and age at baseline.

Outcome measures

Outcome measures
Measure	Donanemab n=786 Participants Participants received 700 mg Donanemab Q4W x 3 doses, then 1400 mg Q4W given IV for up to 72 weeks	Placebo n=831 Participants Participants received placebo given IV.
Change From Baseline in Brain Volume as Measured by Volumetric Magnetic Resonance Imaging (vMRI) Bilateral Hippocampus	-0.20 cubic centimeter (cm^3) Standard Error 0.005	-0.22 cubic centimeter (cm^3) Standard Error 0.005
Change From Baseline in Brain Volume as Measured by Volumetric Magnetic Resonance Imaging (vMRI) Bilateral Whole Brain	-27.46 cubic centimeter (cm^3) Standard Error 0.409	-20.79 cubic centimeter (cm^3) Standard Error 0.392
Change From Baseline in Brain Volume as Measured by Volumetric Magnetic Resonance Imaging (vMRI) Bilateral Ventricles	10.07 cubic centimeter (cm^3) Standard Error 0.185	7.05 cubic centimeter (cm^3) Standard Error 0.178

SECONDARY outcome

Timeframe: Week 16 to week 20

Population: All randomized participants who received at least one dose of study drug and had evaluable PK data.

The average serum concentration at steady state, calculated as Cav = AUCtau/tau, where tau is the dosing interval (4 weeks). AUCtau/tau was assessed at week 12, 16, 24, 36, 52, 64 and Cav for the dosing interval from week 16 to week 20 is reported.

Outcome measures

Outcome measures
Measure	Donanemab n=853 Participants Participants received 700 mg Donanemab Q4W x 3 doses, then 1400 mg Q4W given IV for up to 72 weeks	Placebo Participants received placebo given IV.
Pharmacokinetics (PK): Average Serum Concentration at Steady State of Donanemab	63 micrograms per milliliter (μg/mL) Geometric Coefficient of Variation 32	—

SECONDARY outcome

Timeframe: Baseline through Week 76

Population: All randomized participants who received at least one dose of study drug and had evaluable anti-drug antibody measurement.

Number of participants with treatment-emergent positive Anti-Donanemab antibodies was summarized by treatment group.

Outcome measures

Outcome measures
Measure	Donanemab n=793 Participants Participants received 700 mg Donanemab Q4W x 3 doses, then 1400 mg Q4W given IV for up to 72 weeks	Placebo n=821 Participants Participants received placebo given IV.
Number or Participants With Anti-Donanemab Antibodies	693 Participants	48 Participants

Adverse Events

Donanemab

Serious events: 148 serious events

Other events: 567 other events

Deaths: 16 deaths

Placebo

Serious events: 138 serious events

Other events: 425 other events

Deaths: 10 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Donanemab n=853 participants at risk Participants received 700 mg Donanemab Q4W x 3 doses, then 1400 mg Q4W given IV for up to 72 weeks.	Placebo n=874 participants at risk Participants received placebo given IV.
Gastrointestinal disorders Diarrhoea	5.0% 43/853 • Number of events 51 • Baseline Up To 76 Weeks plus 57 Days (Follow-up period) Safety Population: All randomized participants who received at least one dose of study drug. There were 25 deaths reported in subject disposition and 26 deaths in All-cause mortality, because 1 participant death occurred in the plus 57-day follow-up period was considered as completer in the study disposition period. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.	5.7% 50/874 • Number of events 56 • Baseline Up To 76 Weeks plus 57 Days (Follow-up period) Safety Population: All randomized participants who received at least one dose of study drug. There were 25 deaths reported in subject disposition and 26 deaths in All-cause mortality, because 1 participant death occurred in the plus 57-day follow-up period was considered as completer in the study disposition period. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
General disorders Fatigue	4.9% 42/853 • Number of events 43 • Baseline Up To 76 Weeks plus 57 Days (Follow-up period) Safety Population: All randomized participants who received at least one dose of study drug. There were 25 deaths reported in subject disposition and 26 deaths in All-cause mortality, because 1 participant death occurred in the plus 57-day follow-up period was considered as completer in the study disposition period. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.	5.1% 45/874 • Number of events 68 • Baseline Up To 76 Weeks plus 57 Days (Follow-up period) Safety Population: All randomized participants who received at least one dose of study drug. There were 25 deaths reported in subject disposition and 26 deaths in All-cause mortality, because 1 participant death occurred in the plus 57-day follow-up period was considered as completer in the study disposition period. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Covid-19	15.2% 130/853 • Number of events 135 • Baseline Up To 76 Weeks plus 57 Days (Follow-up period) Safety Population: All randomized participants who received at least one dose of study drug. There were 25 deaths reported in subject disposition and 26 deaths in All-cause mortality, because 1 participant death occurred in the plus 57-day follow-up period was considered as completer in the study disposition period. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.	17.2% 150/874 • Number of events 157 • Baseline Up To 76 Weeks plus 57 Days (Follow-up period) Safety Population: All randomized participants who received at least one dose of study drug. There were 25 deaths reported in subject disposition and 26 deaths in All-cause mortality, because 1 participant death occurred in the plus 57-day follow-up period was considered as completer in the study disposition period. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
Infections and infestations Urinary tract infection	4.9% 42/853 • Number of events 52 • Baseline Up To 76 Weeks plus 57 Days (Follow-up period) Safety Population: All randomized participants who received at least one dose of study drug. There were 25 deaths reported in subject disposition and 26 deaths in All-cause mortality, because 1 participant death occurred in the plus 57-day follow-up period was considered as completer in the study disposition period. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.	6.4% 56/874 • Number of events 65 • Baseline Up To 76 Weeks plus 57 Days (Follow-up period) Safety Population: All randomized participants who received at least one dose of study drug. There were 25 deaths reported in subject disposition and 26 deaths in All-cause mortality, because 1 participant death occurred in the plus 57-day follow-up period was considered as completer in the study disposition period. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
Injury, poisoning and procedural complications Fall	13.0% 111/853 • Number of events 149 • Baseline Up To 76 Weeks plus 57 Days (Follow-up period) Safety Population: All randomized participants who received at least one dose of study drug. There were 25 deaths reported in subject disposition and 26 deaths in All-cause mortality, because 1 participant death occurred in the plus 57-day follow-up period was considered as completer in the study disposition period. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.	12.5% 109/874 • Number of events 141 • Baseline Up To 76 Weeks plus 57 Days (Follow-up period) Safety Population: All randomized participants who received at least one dose of study drug. There were 25 deaths reported in subject disposition and 26 deaths in All-cause mortality, because 1 participant death occurred in the plus 57-day follow-up period was considered as completer in the study disposition period. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
Injury, poisoning and procedural complications Infusion related reaction	8.6% 73/853 • Number of events 166 • Baseline Up To 76 Weeks plus 57 Days (Follow-up period) Safety Population: All randomized participants who received at least one dose of study drug. There were 25 deaths reported in subject disposition and 26 deaths in All-cause mortality, because 1 participant death occurred in the plus 57-day follow-up period was considered as completer in the study disposition period. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.	0.46% 4/874 • Number of events 7 • Baseline Up To 76 Weeks plus 57 Days (Follow-up period) Safety Population: All randomized participants who received at least one dose of study drug. There were 25 deaths reported in subject disposition and 26 deaths in All-cause mortality, because 1 participant death occurred in the plus 57-day follow-up period was considered as completer in the study disposition period. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
Musculoskeletal and connective tissue disorders Arthralgia	5.7% 49/853 • Number of events 55 • Baseline Up To 76 Weeks plus 57 Days (Follow-up period) Safety Population: All randomized participants who received at least one dose of study drug. There were 25 deaths reported in subject disposition and 26 deaths in All-cause mortality, because 1 participant death occurred in the plus 57-day follow-up period was considered as completer in the study disposition period. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.	4.7% 41/874 • Number of events 44 • Baseline Up To 76 Weeks plus 57 Days (Follow-up period) Safety Population: All randomized participants who received at least one dose of study drug. There were 25 deaths reported in subject disposition and 26 deaths in All-cause mortality, because 1 participant death occurred in the plus 57-day follow-up period was considered as completer in the study disposition period. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
Nervous system disorders Amyloid related imaging abnormality-microhaemorrhages and haemosiderin deposits	19.5% 166/853 • Number of events 225 • Baseline Up To 76 Weeks plus 57 Days (Follow-up period) Safety Population: All randomized participants who received at least one dose of study drug. There were 25 deaths reported in subject disposition and 26 deaths in All-cause mortality, because 1 participant death occurred in the plus 57-day follow-up period was considered as completer in the study disposition period. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.	7.4% 65/874 • Number of events 77 • Baseline Up To 76 Weeks plus 57 Days (Follow-up period) Safety Population: All randomized participants who received at least one dose of study drug. There were 25 deaths reported in subject disposition and 26 deaths in All-cause mortality, because 1 participant death occurred in the plus 57-day follow-up period was considered as completer in the study disposition period. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
Nervous system disorders Amyloid related imaging abnormality-oedema/effusion	23.4% 200/853 • Number of events 270 • Baseline Up To 76 Weeks plus 57 Days (Follow-up period) Safety Population: All randomized participants who received at least one dose of study drug. There were 25 deaths reported in subject disposition and 26 deaths in All-cause mortality, because 1 participant death occurred in the plus 57-day follow-up period was considered as completer in the study disposition period. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.	1.9% 17/874 • Number of events 17 • Baseline Up To 76 Weeks plus 57 Days (Follow-up period) Safety Population: All randomized participants who received at least one dose of study drug. There were 25 deaths reported in subject disposition and 26 deaths in All-cause mortality, because 1 participant death occurred in the plus 57-day follow-up period was considered as completer in the study disposition period. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
Nervous system disorders Dizziness	6.1% 52/853 • Number of events 59 • Baseline Up To 76 Weeks plus 57 Days (Follow-up period) Safety Population: All randomized participants who received at least one dose of study drug. There were 25 deaths reported in subject disposition and 26 deaths in All-cause mortality, because 1 participant death occurred in the plus 57-day follow-up period was considered as completer in the study disposition period. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.	5.5% 48/874 • Number of events 60 • Baseline Up To 76 Weeks plus 57 Days (Follow-up period) Safety Population: All randomized participants who received at least one dose of study drug. There were 25 deaths reported in subject disposition and 26 deaths in All-cause mortality, because 1 participant death occurred in the plus 57-day follow-up period was considered as completer in the study disposition period. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
Nervous system disorders Headache	14.0% 119/853 • Number of events 188 • Baseline Up To 76 Weeks plus 57 Days (Follow-up period) Safety Population: All randomized participants who received at least one dose of study drug. There were 25 deaths reported in subject disposition and 26 deaths in All-cause mortality, because 1 participant death occurred in the plus 57-day follow-up period was considered as completer in the study disposition period. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.	9.8% 86/874 • Number of events 105 • Baseline Up To 76 Weeks plus 57 Days (Follow-up period) Safety Population: All randomized participants who received at least one dose of study drug. There were 25 deaths reported in subject disposition and 26 deaths in All-cause mortality, because 1 participant death occurred in the plus 57-day follow-up period was considered as completer in the study disposition period. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.
Nervous system disorders Superficial siderosis of central nervous system	6.8% 58/853 • Number of events 84 • Baseline Up To 76 Weeks plus 57 Days (Follow-up period) Safety Population: All randomized participants who received at least one dose of study drug. There were 25 deaths reported in subject disposition and 26 deaths in All-cause mortality, because 1 participant death occurred in the plus 57-day follow-up period was considered as completer in the study disposition period. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.	1.1% 10/874 • Number of events 12 • Baseline Up To 76 Weeks plus 57 Days (Follow-up period) Safety Population: All randomized participants who received at least one dose of study drug. There were 25 deaths reported in subject disposition and 26 deaths in All-cause mortality, because 1 participant death occurred in the plus 57-day follow-up period was considered as completer in the study disposition period. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly.

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