Trial Outcomes & Findings for Continued Safety Monitoring of Solanezumab (LY2062430) in Alzheimer's Disease (NCT NCT01127633)

Last Updated: 2019-10-08

Results Overview

The number of participants with 1 or more AEs assessed as related to the study drug and is summarized cumulatively. In addition, the number of participants with 1 or more serious AEs is summarized cumulatively. A serious AE is defined as an event that results in death, initial or prolonged hospitalization, is life-threatening, leads to persistent or significant disability/incapacity, is associated with congenital anomaly/birth defect, or is considered significant by the investigator for any other reason. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

1457 participants

Primary outcome timeframe

Baseline through Week 104

Results posted on

2019-10-08

Participant Flow

Participants who completed one of the feeder studies (Study LZAM (NCT00905372) or Study LZAN (NCT00904683)) were enrolled in this study.

Participant milestones

Participant milestones
Measure	Placebo Participants were from feeder studies (LZAM or LZAN). Placebo administered intravenously every 4 weeks through Week 80.	Solanezumab 400 mg of solanezumab administered once every 4 weeks by intravenous infusion (IV) for up to 8 years.
Overall Study STARTED	723	734
Overall Study Received at Least 1 Dose of Study Drug	723	734
Overall Study COMPLETED	70	61
Overall Study NOT COMPLETED	653	673

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants were from feeder studies (LZAM or LZAN). Placebo administered intravenously every 4 weeks through Week 80.	Solanezumab 400 mg of solanezumab administered once every 4 weeks by intravenous infusion (IV) for up to 8 years.
Overall Study Adverse Event	74	73
Overall Study Death	40	43
Overall Study Lost to Follow-up	4	0
Overall Study Parent/Caregiver Decision	246	228
Overall Study Physician Decision	60	45
Overall Study Withdrawal by Subject	57	72
Overall Study Sponsor Decision	163	195
Overall Study Protocol Violation	8	16
Overall Study Abnormal Lab/ECG Result	0	1
Overall Study Not treated	1	0

Baseline Characteristics

Continued Safety Monitoring of Solanezumab (LY2062430) in Alzheimer's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=723 Participants Participants were from feeder studies (LZAM or LZAN). Placebo administered intravenously every 4 weeks through Week 80.	Solanezumab n=734 Participants 400 mg of solanezumab administered once every 4 weeks by intravenous infusion (IV) for up to 8 years.	Total n=1457 Participants Total of all reporting groups
Age, Continuous	73.10 Years STANDARD_DEVIATION 8.004 • n=5 Participants	72.96 Years STANDARD_DEVIATION 7.766 • n=7 Participants	73.03 Years STANDARD_DEVIATION 7.883 • n=5 Participants
Sex: Female, Male Female	406 Participants n=5 Participants	415 Participants n=7 Participants	821 Participants n=5 Participants
Sex: Female, Male Male	317 Participants n=5 Participants	319 Participants n=7 Participants	636 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	137 Participants n=5 Participants	149 Participants n=7 Participants	286 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	13 Participants n=5 Participants	16 Participants n=7 Participants	29 Participants n=5 Participants
Race (NIH/OMB) White	571 Participants n=5 Participants	566 Participants n=7 Participants	1137 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	3 Participants n=7 Participants	5 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 Argentina	41 Participants n=5 Participants	40 Participants n=7 Participants	81 Participants n=5 Participants
Region of Enrollment United States	264 Participants n=5 Participants	243 Participants n=7 Participants	507 Participants n=5 Participants
Region of Enrollment Japan	69 Participants n=5 Participants	87 Participants n=7 Participants	156 Participants n=5 Participants
Region of Enrollment United Kingdom	17 Participants n=5 Participants	18 Participants n=7 Participants	35 Participants n=5 Participants
Region of Enrollment Spain	15 Participants n=5 Participants	22 Participants n=7 Participants	37 Participants n=5 Participants
Region of Enrollment Russia	13 Participants n=5 Participants	15 Participants n=7 Participants	28 Participants n=5 Participants
Region of Enrollment Canada	38 Participants n=5 Participants	40 Participants n=7 Participants	78 Participants n=5 Participants
Region of Enrollment South Korea	33 Participants n=5 Participants	32 Participants n=7 Participants	65 Participants n=5 Participants
Region of Enrollment Sweden	21 Participants n=5 Participants	15 Participants n=7 Participants	36 Participants n=5 Participants
Region of Enrollment Taiwan	26 Participants n=5 Participants	23 Participants n=7 Participants	49 Participants n=5 Participants
Region of Enrollment Poland	18 Participants n=5 Participants	25 Participants n=7 Participants	43 Participants n=5 Participants
Region of Enrollment Brazil	38 Participants n=5 Participants	34 Participants n=7 Participants	72 Participants n=5 Participants
Region of Enrollment Italy	41 Participants n=5 Participants	45 Participants n=7 Participants	86 Participants n=5 Participants
Region of Enrollment Australia	30 Participants n=5 Participants	30 Participants n=7 Participants	60 Participants n=5 Participants
Region of Enrollment France	22 Participants n=5 Participants	23 Participants n=7 Participants	45 Participants n=5 Participants
Region of Enrollment Germany	37 Participants n=5 Participants	42 Participants n=7 Participants	79 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline through Week 104

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

Outcome measures

Outcome measures
Measure	Placebo n=723 Participants Participants were from feeder studies (LZAM or LZAN). Placebo administered intravenously every 4 weeks through Week 80.	Solanezumab n=734 Participants 400 mg of solanezumab administered once every 4 weeks by intravenous infusion (IV) for up to 8 years.
Assess the Number of Participants With One or More Drug-Related Adverse Events (AEs) or Any Serious AEs (SAEs) SAE	308 participants	299 participants
Assess the Number of Participants With One or More Drug-Related Adverse Events (AEs) or Any Serious AEs (SAEs) Other AE	485 participants	514 participants

SECONDARY outcome

Timeframe: Baseline, Week 104

Population: Feeder Intent-to-Treat Population: All randomized participants from feeder studies, who received at least one dose of study drug and had baseline \& at least one post baseline observation for ADAS-Cog14.

ADAS-Cog14 is ADAS-Cog11 augmented with delayed free recall, digit cancellation, and maze completion measures. A score of 0 to 10 for delayed free recall and a conversion code of 0 to 5 for digit cancellation and maze completion provide total score ranges for this extended ADAS-Cog14 of 0 to 90. Higher scores indicate greater disease severity. Least Squares (LS) Mean was determined by mixed model repeated measures (MMRM) methodology with baseline, pooled investigator, treatment, visit, feeder visit 1 Mini-Mental State Examination (MMSE) status (mild/moderate), concomitant acetylcholinesterase inhibitors (AChEI)/Memantine use at baseline (yes/no), baseline age and treatment\*visit.

Outcome measures

Outcome measures
Measure	Placebo n=409 Participants Participants were from feeder studies (LZAM or LZAN). Placebo administered intravenously every 4 weeks through Week 80.	Solanezumab n=451 Participants 400 mg of solanezumab administered once every 4 weeks by intravenous infusion (IV) for up to 8 years.
Change From Baseline to 104-week Endpoint in Alzheimer's Disease Assessment Scale - Cognitive 14-Item Scale (ADAS-Cog14)	17.58 Units on a scale Standard Error 0.532	17.56 Units on a scale Standard Error 0.517

SECONDARY outcome

Timeframe: Baseline, Week 104

ADCS-ADL is a 23-item inventory developed as a Rater-administered questionnaire answered by the participant's caregiver. It measures performance of basic and instrumental activities of daily living by participants. The total score ranges from 0 to 78, with lower scores indicating greater disease severity. LS Mean was determined by MMRM methodology with baseline, pooled investigator, treatment, visit, feeder visit 1 MMSE status (mild/moderate), concomitant AChEI/Memantine use at baseline (yes/no), baseline age and treatment\*visit.

Outcome measures

Outcome measures
Measure	Placebo n=420 Participants Participants were from feeder studies (LZAM or LZAN). Placebo administered intravenously every 4 weeks through Week 80.	Solanezumab n=456 Participants 400 mg of solanezumab administered once every 4 weeks by intravenous infusion (IV) for up to 8 years.
Change From Baseline to 104-week Endpoint in Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL)	-26.77 Units on a scale Standard Error 0.888	-24.77 Units on a scale Standard Error 0.871

SECONDARY outcome

Timeframe: Baseline, Week 104

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 was determined by MMRM methodology with baseline, pooled investigator, treatment, visit, feeder visit 1 MMSE status (mild/moderate), concomitant AChEI/Memantine use at baseline (yes/no), baseline age and treatment\*visit.

Outcome measures

Outcome measures
Measure	Placebo n=416 Participants Participants were from feeder studies (LZAM or LZAN). Placebo administered intravenously every 4 weeks through Week 80.	Solanezumab n=452 Participants 400 mg of solanezumab administered once every 4 weeks by intravenous infusion (IV) for up to 8 years.
Change From Baseline to 104-week Endpoint in Clinical Dementia Rating - Sum of Boxes (CDR-SB)	5.59 Units on a scale Standard Error 0.174	5.27 Units on a scale Standard Error 0.169

SECONDARY outcome

Timeframe: Baseline, Week 104

The NPI is a questionnaire administered to caregivers that quantifies behavioral changes in dementia. Each of the 12 behavioral domains the caregiver reports as present are scored for Frequency, scale: 1 (Occasionally) to 4 (Very Frequently), and Severity, scale: 1 (Mild) to 3 (Severe). If the domain is reported by the caregiver as 'Not Affected,' that domain is scored as 0. The individual domain scores are calculated by multiplying the frequency times the severity for each domain. NPI Total Score is calculated by adding the individual domain scores together for all 12 domains, with a scores range from 0 to 144. Lower scores indicated less severity and higher scores indicated a greater severity of neuropsychiatric disturbance. LS Mean was determined by MMRM methodology with baseline, pooled investigator, treatment, visit, concomitant AChEI/Memantine use at baseline (yes/no), baseline age and treatment\*visit.

Outcome measures

Outcome measures
Measure	Placebo n=414 Participants Participants were from feeder studies (LZAM or LZAN). Placebo administered intravenously every 4 weeks through Week 80.	Solanezumab n=457 Participants 400 mg of solanezumab administered once every 4 weeks by intravenous infusion (IV) for up to 8 years.
Change From Baseline to 104-week Endpoint in Neuropsychiatric Inventory (NPI) Mild Alzheimer's Disease	4.49 Units on a scale Standard Error 0.788	5.41 Units on a scale Standard Error 0.773
Change From Baseline to 104-week Endpoint in Neuropsychiatric Inventory (NPI) Moderate Alzheimer's Disease	11.90 Units on a scale Standard Error 1.517	8.10 Units on a scale Standard Error 1.427

SECONDARY outcome

Timeframe: Baseline, Week 104

The RUD-Lite is a caregiver-completed assessment designed to assess the amount of formal and informal resources used by participants and the primary caregiver. It is completed by the caregiver and compiles data on the following resources: length of time the caregiver spends giving care, assisting participants with basic activities of daily living (BADL: eating dressing, grooming, bathing); assisting participants with instrumental activities of daily living (IADLs: shopping, cooking, housekeeping, laundry, transportation, taking medication, managing finances), and providing supervision. Scores range from 0 to 24 hours. Higher values indicate greater resource use. LS Mean was determined by MMRM methodology with baseline, pooled investigator, treatment, visit, concomitant AChEI/Memantine use at baseline (yes/no), baseline age and treatment\*visit.

Outcome measures

Outcome measures
Measure	Placebo n=415 Participants Participants were from feeder studies (LZAM or LZAN). Placebo administered intravenously every 4 weeks through Week 80.	Solanezumab n=451 Participants 400 mg of solanezumab administered once every 4 weeks by intravenous infusion (IV) for up to 8 years.
Change From Baseline to 104-week Endpoint in Resource Utilization in Dementia - Lite (RUD-Lite) Caregiver Hours Mild Alzheimer's Disease-Basic ADL	1.96 hours per day (hr/day) Standard Error 0.184	1.21 hours per day (hr/day) Standard Error 0.182
Change From Baseline to 104-week Endpoint in Resource Utilization in Dementia - Lite (RUD-Lite) Caregiver Hours Mild Alzheimer's Disease-Instrumental ADL	1.65 hours per day (hr/day) Standard Error 0.207	1.05 hours per day (hr/day) Standard Error 0.205
Change From Baseline to 104-week Endpoint in Resource Utilization in Dementia - Lite (RUD-Lite) Caregiver Hours Mild Alzheimer's Disease-Supervision	2.84 hours per day (hr/day) Standard Error 0.368	2.59 hours per day (hr/day) Standard Error 0.361
Change From Baseline to 104-week Endpoint in Resource Utilization in Dementia - Lite (RUD-Lite) Caregiver Hours Moderate Alzheimer's Disease-Basic ADL	3.19 hours per day (hr/day) Standard Error 0.461	3.54 hours per day (hr/day) Standard Error 0.436
Change From Baseline to 104-week Endpoint in Resource Utilization in Dementia - Lite (RUD-Lite) Caregiver Hours Moderate Alzheimer's Disease-Instrumental ADL	1.75 hours per day (hr/day) Standard Error 0.461	1.72 hours per day (hr/day) Standard Error 0.433
Change From Baseline to 104-week Endpoint in Resource Utilization in Dementia - Lite (RUD-Lite) Caregiver Hours Moderate Alzheimer's Disease-Supervision	5.03 hours per day (hr/day) Standard Error 0.693	4.47 hours per day (hr/day) Standard Error 0.654

SECONDARY outcome

Timeframe: Baseline, Week 104

EQ-5D (proxy version) is a generic, multidimensional, health-related, quality-of-life instrument assessing caregiver's impression of participants overall health state. Profile allows caregivers to rate participant's health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood using a 3-level scale: 1 (no problem), 2 (some problems), and 3 (major problems). These attribute combinations are converted into a weighted Health-State Index Score according to the United States (US) population-based algorithm. EQ-5D US Population-Based Index Scores range from -0.11 to 1.0. A score of 1.0 indicated perfect health. The Overall Health State Index Score is caregiver-reported using a visual analogue scale marked 0 (worst imaginable health) to 100 (best imaginable health state). LS Mean was determined by MMRM methodology with baseline, pooled investigator, treatment, visit, concomitant AChEI/Memantine use at baseline (yes/no), baseline age and treatment\*visit.

Outcome measures

Outcome measures
Measure	Placebo n=414 Participants Participants were from feeder studies (LZAM or LZAN). Placebo administered intravenously every 4 weeks through Week 80.	Solanezumab n=453 Participants 400 mg of solanezumab administered once every 4 weeks by intravenous infusion (IV) for up to 8 years.
Change From Baseline to 104-week Endpoint in EuroQol 5-Dimensional Health-Related Quality of Life Scale Proxy Version (EQ-5D Proxy) Mild Alzheimer's Disease	-0.07 Units on a scale Standard Error 0.010	-0.06 Units on a scale Standard Error 0.009
Change From Baseline to 104-week Endpoint in EuroQol 5-Dimensional Health-Related Quality of Life Scale Proxy Version (EQ-5D Proxy) Moderate Alzheimer's Disease	-0.16 Units on a scale Standard Error 0.020	-0.16 Units on a scale Standard Error 0.019

SECONDARY outcome

Timeframe: Baseline, Week 104

The QoL-AD (Caregiver Total Score) is a disease-specific measure of quality of life for an Alzheimer's Disease (AD) population administered to the participant's primary caregiver, who answers on behalf of the participant. The assessment consists of 13 items covering physical health, energy, mood, living situations, memory, family, marriage, friends, chores, fun, money, self and life as a whole. The assessment is scored on a 4-point Likert scale with scores ranging from 1 (poor) to 4 (excellent). QoL-AD Total Score is defined as the sum of the 13 items with a scores range from 13 to 52. Higher scores denote a better quality of life. LS Mean was determined by MMRM methodology with baseline, pooled investigator, treatment, visit, concomitant AChEI/Memantine use at baseline (yes/no), baseline age and treatment\*visit.

Outcome measures

Outcome measures
Measure	Placebo n=387 Participants Participants were from feeder studies (LZAM or LZAN). Placebo administered intravenously every 4 weeks through Week 80.	Solanezumab n=413 Participants 400 mg of solanezumab administered once every 4 weeks by intravenous infusion (IV) for up to 8 years.
Change From Baseline to 104-week Endpoint in Quality of Life in Alzheimer's Disease (QoL-AD) QLAD Self-Report Total Score-Mild Alzheimer's	-1.37 Units on a scale Standard Error 0.331	-0.98 Units on a scale Standard Error 0.327
Change From Baseline to 104-week Endpoint in Quality of Life in Alzheimer's Disease (QoL-AD) QLAD Caregiver Total Score-Mild Alzheimer's	-3.28 Units on a scale Standard Error 0.350	-3.63 Units on a scale Standard Error 0.345
Change From Baseline to 104-week Endpoint in Quality of Life in Alzheimer's Disease (QoL-AD) QLAD Self-Report Total Score-Moderate Alzheimer's	-2.52 Units on a scale Standard Error 0.605	-2.34 Units on a scale Standard Error 0.585
Change From Baseline to 104-week Endpoint in Quality of Life in Alzheimer's Disease (QoL-AD) QLAD Caregiver Total Score-Moderate Alzheimer's	-4.26 Units on a scale Standard Error 0.573	-3.14 Units on a scale Standard Error 0.552

SECONDARY outcome

Timeframe: Baseline, Week 104

The MMSE is an instrument used to assess a participant's cognitive function. The instrument is divided into 2 sections. The first section measures orientation, memory, and attention with scores ranging from 0 to 21 (lower scores indicate greater impairment). The second section tests the ability of the participant to name objects, follow verbal and written commands, write a sentence, and copy figures with scores ranging from 0 to 9 (lower scores indicate greater impairment). The range for MMSE Total Score is 0 to 30. Lower scores indicate more impairment. LS Mean was determined by MMRM methodology with baseline, pooled investigator, treatment, visit, concomitant AChEI/Memantine use at baseline (yes/no), baseline age and treatment\*visit.

Outcome measures

Outcome measures
Measure	Placebo n=412 Participants Participants were from feeder studies (LZAM or LZAN). Placebo administered intravenously every 4 weeks through Week 80.	Solanezumab n=446 Participants 400 mg of solanezumab administered once every 4 weeks by intravenous infusion (IV) for up to 8 years.
Change From Baseline to 104-week Endpoint in Mini-Mental State Examination (MMSE)	-8.08 Units on a scale Standard Error 0.270	-7.60 Units on a scale Standard Error 0.263

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: All Feeder Intent-to-Treat Population: All randomized participants from feeder studies, who received at least one dose of study drug and had baseline \& at least one post baseline observation for plasma Aβ 1-40 and Aβ 1-42.

Concentration of the peptide Aβ 1-40 and Aβ 1-42 in plasma measured by immunoassay. The immunoassays for plasma Aβ 1-40 and Aβ 1-42 peptides were modified to render them tolerant to the presence of Solanezumab which would otherwise interfere with non-modified assays. LS Mean was determined by MMRM methodology with baseline, pooled investigator, treatment, visit, feeder visit 1 MMSE status (mild/moderate), concomitant AChEI/Memantine use at baseline (yes/no), baseline age and treatment\*visit.

Outcome measures

Outcome measures
Measure	Placebo n=515 Participants Participants were from feeder studies (LZAM or LZAN). Placebo administered intravenously every 4 weeks through Week 80.	Solanezumab n=532 Participants 400 mg of solanezumab administered once every 4 weeks by intravenous infusion (IV) for up to 8 years.
Change From Baseline to 52-week Endpoint in Plasma Amyloid Beta (Aβ) Levels Aβ 1-40-Mild Alzheimer's Disease	176412.04 picograms per milliliter (pg/mL) Standard Error 3718.292	173064.99 picograms per milliliter (pg/mL) Standard Error 3717.695
Change From Baseline to 52-week Endpoint in Plasma Amyloid Beta (Aβ) Levels Aβ 1-42-Mild Alzheimer's Disease	19854.92 picograms per milliliter (pg/mL) Standard Error 366.392	19723.48 picograms per milliliter (pg/mL) Standard Error 368.644
Change From Baseline to 52-week Endpoint in Plasma Amyloid Beta (Aβ) Levels Aβ 1-40-Moderate Alzheimer's Disease	169356 picograms per milliliter (pg/mL) Standard Error 4627.8	169087 picograms per milliliter (pg/mL) Standard Error 4511.6
Change From Baseline to 52-week Endpoint in Plasma Amyloid Beta (Aβ) Levels Aβ 1-42-Moderate Alzheimer's Disease	19237 picograms per milliliter (pg/mL) Standard Error 556.3	19552 picograms per milliliter (pg/mL) Standard Error 528.7

SECONDARY outcome

Timeframe: Baseline, Week 104

The vMRI assessment of right and left hippocampal volume is reported. LS Mean was determined by MMRM methodology with baseline, pooled investigator, treatment, visit, feeder visit 1 MMSE status (mild/moderate), concomitant AChEI/Memantine use at baseline (yes/no), baseline age and treatment\*visit.

Outcome measures

Outcome measures
Measure	Placebo n=310 Participants Participants were from feeder studies (LZAM or LZAN). Placebo administered intravenously every 4 weeks through Week 80.	Solanezumab n=325 Participants 400 mg of solanezumab administered once every 4 weeks by intravenous infusion (IV) for up to 8 years.
Change From Baseline to 104-week Endpoint in Volumetric Magnetic Resonance Imaging (vMRI) Right hippocampal volume-Mild Alzheimer's Disease	-230.23 Cubic millimeter (mm³) Standard Error 8.232	-230.07 Cubic millimeter (mm³) Standard Error 8.195
Change From Baseline to 104-week Endpoint in Volumetric Magnetic Resonance Imaging (vMRI) Left hippocampal volume-Mild Alzheimer's Disease	-257.15 Cubic millimeter (mm³) Standard Error 8.153	-244.00 Cubic millimeter (mm³) Standard Error 8.115
Change From Baseline to 104-week Endpoint in Volumetric Magnetic Resonance Imaging (vMRI) Right hippocampal volume-Moderate Alzheimer's	-261.39 Cubic millimeter (mm³) Standard Error 11.796	-256.52 Cubic millimeter (mm³) Standard Error 11.246
Change From Baseline to 104-week Endpoint in Volumetric Magnetic Resonance Imaging (vMRI) Left hippocampal volume-Moderate Alzheimer's	-255.16 Cubic millimeter (mm³) Standard Error 11.466	-253.29 Cubic millimeter (mm³) Standard Error 10.858

SECONDARY outcome

Timeframe: Baseline, Week 104

The cognitive subscale of the ADAS (ADAS Cog11) was used as a primary efficacy measure and consists of 11 items assessing areas of function most typically impaired in Alzheimer's disease: orientation, verbal memory, language, and praxis. The scale ranges from 0 to 70, with higher scores indicating greater disease severity. LS Mean was determined by MMRM methodology with baseline, pooled investigator, treatment, visit, feeder visit 1 MMSE status (mild/moderate), concomitant AChEI/Memantine use at baseline (yes/no), baseline age and treatment\*visit.

Outcome measures

Outcome measures
Measure	Placebo n=375 Participants Participants were from feeder studies (LZAM or LZAN). Placebo administered intravenously every 4 weeks through Week 80.	Solanezumab n=409 Participants 400 mg of solanezumab administered once every 4 weeks by intravenous infusion (IV) for up to 8 years.
Change From Baseline to 104-week Endpoint in Alzheimer's Disease Assessment Scale - Cognitive Subscore 11-Item Scale (ADAS-Cog11)	17.78 units on a scale Standard Error 0.595	17.38 units on a scale Standard Error 0.580

SECONDARY outcome

Timeframe: Baseline, Week 104

Population: Feeder Intent-to-Treat Population: All randomized participants with mild Alzheimer's Disease from feeder studies, who received at least one dose of study drug and had baseline \& at least one post baseline observation for Amyloid Plaque Burden.

Florbetapir PET imaging was used to test for change from baseline. The hypothesis that amyloid burden was reduced in participants between the treatment groups from the feeder studies was tested. The change from baseline to the postbaseline visit of the composite summary standard uptake value ratio of florbetapir F18 was calculated. The composite summary measure is an unweighted average of the 6 smaller regions (anterior cingulate, frontal medial orbital, parietal, posterior cingulate, precuneus, and temporal) normalized to whole cerebellum and to subject-specific white matter.

Outcome measures

Outcome measures
Measure	Placebo n=42 Participants Participants were from feeder studies (LZAM or LZAN). Placebo administered intravenously every 4 weeks through Week 80.	Solanezumab n=48 Participants 400 mg of solanezumab administered once every 4 weeks by intravenous infusion (IV) for up to 8 years.
Mean Change From Baseline to Endpoint in Amyloid Imaging Parameters in Subjects With Mild Alzheimer's Disease	0.00 Standard Uptake Value ratio (SUVr) Standard Deviation 0.131	-0.01 Standard Uptake Value ratio (SUVr) Standard Deviation 0.222

Adverse Events

Placebo

Serious events: 308 serious events

Other events: 485 other events

Deaths: 0 deaths

Solanezumab

Serious events: 299 serious events

Other events: 514 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Placebo n=723 participants at risk Participants were from feeder studies (LZAM or LZAN). Placebo administered intravenously every 4 weeks through Week 80.	Solanezumab n=734 participants at risk 400 mg of solanezumab administered once every 4 weeks by intravenous infusion (IV) for up to 8 years.
Gastrointestinal disorders Constipation	7.1% 51/723 • Number of events 56 There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	8.7% 64/734 • Number of events 71 There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Gastrointestinal disorders Diarrhoea	8.0% 58/723 • Number of events 72 There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	10.4% 76/734 • Number of events 105 There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Gastrointestinal disorders Vomiting	5.7% 41/723 • Number of events 51 There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	6.9% 51/734 • Number of events 70 There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
General disorders Oedema peripheral	4.3% 31/723 • Number of events 33 There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	5.0% 37/734 • Number of events 38 There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Infections and infestations Bronchitis	4.4% 32/723 • Number of events 47 There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	5.9% 43/734 • Number of events 56 There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Infections and infestations Nasopharyngitis	10.8% 78/723 • Number of events 129 There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	12.0% 88/734 • Number of events 145 There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Infections and infestations Upper respiratory tract infection	8.2% 59/723 • Number of events 73 There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	6.4% 47/734 • Number of events 61 There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Infections and infestations Urinary tract infection	13.6% 98/723 • Number of events 153 There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	11.4% 84/734 • Number of events 161 There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Injury, poisoning and procedural complications Contusion	6.2% 45/723 • Number of events 62 There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	7.9% 58/734 • Number of events 84 There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Injury, poisoning and procedural complications Fall	20.1% 145/723 • Number of events 222 There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	18.5% 136/734 • Number of events 245 There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Investigations Weight decreased	6.6% 48/723 • Number of events 51 There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	5.2% 38/734 • Number of events 40 There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Metabolism and nutrition disorders Decreased appetite	4.8% 35/723 • Number of events 39 There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	5.0% 37/734 • Number of events 44 There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Musculoskeletal and connective tissue disorders Arthralgia	5.8% 42/723 • Number of events 51 There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	4.5% 33/734 • Number of events 40 There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Musculoskeletal and connective tissue disorders Back pain	6.8% 49/723 • Number of events 54 There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	9.1% 67/734 • Number of events 75 There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Nervous system disorders Cerebral microhaemorrhage	5.8% 42/723 • Number of events 47 There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	7.6% 56/734 • Number of events 61 There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Nervous system disorders Dizziness	5.4% 39/723 • Number of events 43 There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	5.9% 43/734 • Number of events 53 There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Nervous system disorders Headache	6.8% 49/723 • Number of events 65 There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	6.3% 46/734 • Number of events 64 There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Psychiatric disorders Agitation	10.4% 75/723 • Number of events 83 There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	8.7% 64/734 • Number of events 72 There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Psychiatric disorders Anxiety	7.7% 56/723 • Number of events 78 There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	11.7% 86/734 • Number of events 114 There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Psychiatric disorders Insomnia	9.3% 67/723 • Number of events 70 There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	10.1% 74/734 • Number of events 80 There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Reproductive system and breast disorders Benign prostatic hyperplasia	5.4% 17/317 • Number of events 17 There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	2.8% 9/319 • Number of events 10 There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Cough	6.9% 50/723 • Number of events 61 There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	9.0% 66/734 • Number of events 74 There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Vascular disorders Hypertension	5.8% 42/723 • Number of events 43 There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	4.9% 36/734 • Number of events 38 There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.