Trial Outcomes & Findings for Amyloid Imaging And Safety Study Of ACC-001 In Subjects With Early Alzheimer's Disease (NCT NCT01227564)

NCT ID: NCT01227564

Last Updated: 2016-02-25

Results Overview

Fibrillar brain Aβ was measured by retention of florbetapir F18 as measured by positron emission tomography (PET) scans. A positive change indicating an improvement from baseline.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 63 participants
• Primary outcome timeframe: 104 weeks
• Results posted on: 2016-02-25

Participant Flow

Twenty study centers in the United States of America participated. One of these did not enroll any participants.

Participants, who were found eligible, were randomized to 1 of 3 groups in a 1:1:1 ratio between ACC-001 3 μg+QS-21, or ACC-001 10 μg+QS-21, or placebo (which was administrated as phosphate buffered saline [PBS]). The study randomization was stratified based on apolipoprotein E (Apo E) genotype (E4 carrier or non-carrier).

Participant milestones

Measure	ACC 3 μg+QS-21 Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	ACC 10 μg+QS-21 Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Placebo Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Overall Study STARTED	22	20	21
Overall Study Treated	22	20	21
Overall Study Completed Treatment	21	18	17
Overall Study COMPLETED	18	18	15
Overall Study NOT COMPLETED	4	2	6

Reasons for withdrawal

Measure	ACC 3 μg+QS-21 Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	ACC 10 μg+QS-21 Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Placebo Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Overall Study No Longer Willing to Participate	4	2	5
Overall Study Participant moved to another town	0	0	1

Baseline Characteristics

Amyloid Imaging And Safety Study Of ACC-001 In Subjects With Early Alzheimer's Disease

Baseline characteristics by cohort

Measure	ACC 3 μg+QS-21 n=22 Participants Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	ACC 10 μg+QS-21 n=20 Participants Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Placebo n=21 Participants Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Total n=63 Participants Total of all reporting groups
Age, Continuous	66.8 years STANDARD_DEVIATION 7.31 • n=5 Participants	68.5 years STANDARD_DEVIATION 7.02 • n=7 Participants	69.6 years STANDARD_DEVIATION 6.82 • n=5 Participants	68.3 years STANDARD_DEVIATION 7.04 • n=4 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	13 Participants n=7 Participants	9 Participants n=5 Participants	33 Participants n=4 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants	30 Participants n=4 Participants
MMSE Score	27.3 score STANDARD_DEVIATION 1.64 • n=5 Participants	27.7 score STANDARD_DEVIATION 1.63 • n=7 Participants	28.0 score STANDARD_DEVIATION 1.47 • n=5 Participants	27.6 score STANDARD_DEVIATION 1.58 • n=4 Participants

PRIMARY outcome

Timeframe: 104 weeks

Population: The full analysis set (FAS) population included all randomized participants who had at least one dose of investigational product.

Fibrillar brain Aβ was measured by retention of florbetapir F18 as measured by positron emission tomography (PET) scans. A positive change indicating an improvement from baseline.

Outcome measures

Measure	ACC 3 μg+QS-21 n=22 Participants Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	ACC 10 μg+QS-21 n=20 Participants Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Overall ACC + QS21 n=42 Participants Participants received either 3 μg of ACC-001 and 50 μg of QS-21 or 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Placebo n=21 Participants Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Change From Baseline in Brain Fibrillar Beta-Amyloid Protein (Aβ) at Week 104 as Measured by Standard Uptake Value Ratios (SUVRs) Over the Composite Regions of Interest (ROIs) Week 52 (N: 22, 19, 41, 20)	0.009 ratio Interval -0.042 to 0.06	0.017 ratio Interval -0.039 to 0.073	0.013 ratio Interval -0.025 to 0.051	0.011 ratio Interval -0.043 to 0.065
Change From Baseline in Brain Fibrillar Beta-Amyloid Protein (Aβ) at Week 104 as Measured by Standard Uptake Value Ratios (SUVRs) Over the Composite Regions of Interest (ROIs) Week 78 (N: 21, 18, 39, 16)	-0.011 ratio Interval -0.084 to 0.062	-0.022 ratio Interval -0.101 to 0.057	-0.017 ratio Interval -0.071 to 0.038	-0.014 ratio Interval -0.096 to 0.068
Change From Baseline in Brain Fibrillar Beta-Amyloid Protein (Aβ) at Week 104 as Measured by Standard Uptake Value Ratios (SUVRs) Over the Composite Regions of Interest (ROIs) Week 104 (N: 14, 15, 29, 13)	-0.018 ratio Interval -0.097 to 0.061	-0.018 ratio Interval -0.098 to 0.062	-0.018 ratio Interval -0.075 to 0.038	0.032 ratio Interval -0.052 to 0.115

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 80 or Week 104

Population: FAS population included all randomized participants who had at least one dose of investigational product.

For the majority of the participants, the lumbar puncture for the first CSF sample was collected up to 3 days prior to injection of investigational product. For the participants who had a CSF being already drawn at week 80, no CSF sample was drawn at week 104, nor at the Early termination (ET) visit. For those participants who early terminated the study before week 80, CSF was drawn at ET visit.

Outcome measures

Measure	ACC 3 μg+QS-21 n=22 Participants Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	ACC 10 μg+QS-21 n=18 Participants Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Overall ACC + QS21 n=40 Participants Participants received either 3 μg of ACC-001 and 50 μg of QS-21 or 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Placebo n=17 Participants Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Change From Baseline in Cerebrospinal Fluid (CSF) Aβ x-40	192.93 μg/ml Interval -652.96 to 1038.82	726.74 μg/ml Interval -252.11 to 1705.58	459.83 μg/ml Interval -178.24 to 1097.91	144.76 μg/ml Interval -816.2 to 1105.71

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 80 or Week 104

Population: FAS population included all randomized participants who had at least one dose of investigational product.

For the majority of the participants, the lumbar puncture for the first CSF sample was collected up to 3 days prior to injection of investigational product. For the participants who had a CSF being already drawn at week 80, no CSF sample was drawn at week 104, nor at ET visit. For those participants who early terminated the study before week 80, CSF was drawn at ET visit.

Outcome measures

Measure	ACC 3 μg+QS-21 n=22 Participants Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	ACC 10 μg+QS-21 n=18 Participants Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Overall ACC + QS21 n=40 Participants Participants received either 3 μg of ACC-001 and 50 μg of QS-21 or 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Placebo n=17 Participants Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Change From Baseline in CSF Aβ x-42	15.29 μg/ml Interval -43.14 to 73.71	75.55 μg/ml Interval 11.89 to 139.21	45.42 μg/ml Interval 1.56 to 89.28	-8.87 μg/ml Interval -75.24 to 57.5

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 80 or Week 104

Population: FAS population included all randomized participants who had at least one dose of investigational product.

For the majority of the participants, the lumbar puncture for the first CSF sample was collected up to 3 days prior to injection of investigational product. For the participants who had a CSF being already drawn at week 80, no CSF sample was drawn at week 104, nor at ET visit. For those participants who early terminated the study before week 80, CSF was drawn at ET visit.

Outcome measures

Measure	ACC 3 μg+QS-21 n=22 Participants Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	ACC 10 μg+QS-21 n=18 Participants Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Overall ACC + QS21 n=40 Participants Participants received either 3 μg of ACC-001 and 50 μg of QS-21 or 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Placebo n=17 Participants Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Change From Baseline in CSF p-Tau	-2.32 μg/ml Interval -6.8 to 2.15	-3.47 μg/ml Interval -8.43 to 1.49	-2.90 μg/ml Interval -6.14 to 0.35	1.03 μg/ml Interval -3.89 to 5.96

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 80 or Week 104

Population: FAS population included all randomized participants who had at least one dose of investigational product.

For the majority of the participants, the lumbar puncture for the first CSF sample was collected up to 3 days prior to injection of investigational product. For the participants who had a CSF being already drawn at week 80, no CSF sample was drawn at week 104, nor at ET visit. For those participants who early terminated the study before week 80, CSF was drawn at ET visit.

Outcome measures

Measure	ACC 3 μg+QS-21 n=22 Participants Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	ACC 10 μg+QS-21 n=18 Participants Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Overall ACC + QS21 n=40 Participants Participants received either 3 μg of ACC-001 and 50 μg of QS-21 or 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Placebo n=17 Participants Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Change From Baseline in CSF Total Tau	25.56 μg/ml Interval -24.38 to 75.5	-27.48 μg/ml Interval -83.48 to 28.49	-0.96 μg/ml Interval -37.23 to 35.31	55.92 μg/ml Interval 0.97 to 110.86

OTHER_PRE_SPECIFIED outcome

Timeframe: 104 weeks

Population: FAS population included all randomized participants who had at least one dose of investigational product.

Site personnel collecting the samples for plasma Aβ (x-40) concentrations and the results were blinded to the participant treatment group assignment.

Outcome measures

Measure	ACC 3 μg+QS-21 n=22 Participants Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	ACC 10 μg+QS-21 n=20 Participants Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Overall ACC + QS21 n=42 Participants Participants received either 3 μg of ACC-001 and 50 μg of QS-21 or 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Placebo n=21 Participants Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Change From Baseline in Plasma Aβ x-40 Week 12 (N: 22, 19, 41, 20)	30.42 pg/mL Interval -9.8 to 70.63	61.70 pg/mL Interval 18.55 to 104.85	46.06 pg/mL Interval 16.49 to 75.63	10.64 pg/mL Interval -31.24 to 52.52
Change From Baseline in Plasma Aβ x-40 Week 26 (N: 22, 18, 40, 19)	150.51 pg/mL Interval 45.32 to 255.7	276.86 pg/mL Interval 162.5 to 391.66	213.68 pg/mL Interval 135.8 to 291.57	51.22 pg/mL Interval -61.16 to 163.6
Change From Baseline in Plasma Aβ x-40 Week 52 (N: 22, 18, 40, 19)	252.87 pg/mL Interval 166.03 to 339.72	313.34 pg/mL Interval 218.29 to 408.38	283.11 pg/mL Interval 218.68 to 347.53	138.74 pg/mL Interval 45.73 to 231.75
Change From Baseline in Plasma Aβ x-40 Week 78 (N: 22, 17, 39, 17)	225.15 pg/mL Interval 105.18 to 345.11	344.13 pg/mL Interval 210.8 to 477.45	284.64 pg/mL Interval 194.93 to 374.35	117.31 pg/mL Interval -13.47 to 248.08
Change From Baseline in Plasma Aβ x-40 Week 104 (N: 18, 17, 35, 13)	216.51 pg/mL Interval 111.67 to 321.35	279.00 pg/mL Interval 164.37 to 393.63	247.76 pg/mL Interval 170.03 to 325.48	74.60 pg/mL Interval -42.18 to 191.37

OTHER_PRE_SPECIFIED outcome

Timeframe: 104 weeks

Population: FAS population included all randomized participants who had at least one dose of investigational product.

BBSI measures whole brain atrophy from registered MRI scan pairs, by subtracting the area under the intensity profile across a boundary in the repeat scans from the initial scan (baseline).

Outcome measures

Measure	ACC 3 μg+QS-21 n=22 Participants Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	ACC 10 μg+QS-21 n=20 Participants Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Overall ACC + QS21 n=42 Participants Participants received either 3 μg of ACC-001 and 50 μg of QS-21 or 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Placebo n=21 Participants Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Change From Baseline in Volumetric Brain Magnetic Resonance Imaging (MRI) Measurements in Brain Boundary Shift Integral (BBSI) Week 10 (N: 22, 20, 42, 20)	-4.100 mL Interval -6.85 to -1.351	-0.952 mL Interval -3.84 to 1.935	-2.526 mL Interval -4.544 to -0.509	-1.449 mL Interval -4.316 to 1.419
Change From Baseline in Volumetric Brain Magnetic Resonance Imaging (MRI) Measurements in Brain Boundary Shift Integral (BBSI) Week 24 (N: 22, 20, 42, 21)	-6.080 mL Interval -8.781 to -3.379	-2.357 mL Interval -5.193 to 0.48	-4.218 mL Interval -6.201 to -2.236	-5.906 mL Interval -8.683 to -3.128
Change From Baseline in Volumetric Brain Magnetic Resonance Imaging (MRI) Measurements in Brain Boundary Shift Integral (BBSI) Week 50 (N: 22, 19, 41, 18)	-12.329 mL Interval -15.812 to -8.846	-5.926 mL Interval -9.64 to -2.213	-9.128 mL Interval -11.692 to -6.564	-10.684 mL Interval -14.435 to -6.933
Change From Baseline in Volumetric Brain Magnetic Resonance Imaging (MRI) Measurements in Brain Boundary Shift Integral (BBSI) Week 76 (N: 21, 17, 38, 15)	-16.579 mL Interval -21.361 to -11.797	-10.802 mL Interval -16.022 to -5.582	-13.690 mL Interval -17.242 to -10.138	-16.196 mL Interval -21.573 to -10.818
Change From Baseline in Volumetric Brain Magnetic Resonance Imaging (MRI) Measurements in Brain Boundary Shift Integral (BBSI) Week 104 (N: 18, 16, 34, 14)	-20.982 mL Interval -26.683 to -15.101	-12.662 mL Interval -19.008 to -6.316	-16.822 mL Interval -21.128 to -12.486	-18.772 mL Interval -25.335 to -12.209

OTHER_PRE_SPECIFIED outcome

Timeframe: 104 weeks

Population: FAS population included all randomized participants who had at least one dose of investigational product.

VBSI measures ventricular volume change from registered MRI scan pairs, by subtracting the area under the intensity profile across a boundary in the repeat scans.

Outcome measures

Measure	ACC 3 μg+QS-21 n=22 Participants Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	ACC 10 μg+QS-21 n=20 Participants Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Overall ACC + QS21 n=42 Participants Participants received either 3 μg of ACC-001 and 50 μg of QS-21 or 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Placebo n=21 Participants Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Change From Baseline in Volumetric Brain MRI Measurements in Ventricular Boundary Shift Integral (VBSI) Week 10 (N: 22, 20, 42, 20)	0.913 mL Interval 0.5 to 1.327	0.643 mL Interval 0.209 to 1.076	0.778 mL Interval 0.474 to 1.082	0.496 mL Interval 0.056 to 0.935
Change From Baseline in Volumetric Brain MRI Measurements in Ventricular Boundary Shift Integral (VBSI) Week 24 (N: 22, 20, 42, 21)	1.540 mL Interval 1.066 to 2.014	1.229 mL Interval 0.732 to 1.726	1.385 mL Interval 1.038 to 1.731	1.533 mL Interval 1.039 to 2.027
Change From Baseline in Volumetric Brain MRI Measurements in Ventricular Boundary Shift Integral (VBSI) Week 50 (N: 22, 19, 41, 18)	3.023 mL Interval 2.194 to 3.853	2.242 mL Interval 1.364 to 3.12	2.632 mL Interval 2.027 to 3.238	3.038 mL Interval 2.16 to 3.915
Change From Baseline in Volumetric Brain MRI Measurements in Ventricular Boundary Shift Integral (VBSI) Week 76 (N: 22, 17, 39, 16)	4.729 mL Interval 3.322 to 6.136	3.445 mL Interval 1.923 to 4.967	4.087 mL Interval 3.05 to 5.124	4.474 mL Interval 2.94 to 6.008
Change From Baseline in Volumetric Brain MRI Measurements in Ventricular Boundary Shift Integral (VBSI) Week 104 (N: 18, 16, 34, 14)	6.422 mL Interval 4.586 to 8.257	4.970 mL Interval 2.999 to 6.941	5.696 mL Interval 4.348 to 7.043	5.770 mL Interval 3.77 to 7.769

OTHER_PRE_SPECIFIED outcome

Timeframe: 104 weeks

Population: FAS population included all randomized participants who had at least one dose of investigational product.

Left HBSI and Right HBSI respectively measure the left hippocampal atrophy and the right hippocampal atrophy from registered MRI scan pairs, by subtracting the corresponding area under the intensity profile across a boundary in the repeat scans. HBSI (Total) is defined as the summation of the left HBSI and the right HBSI.

Outcome measures

Measure	ACC 3 μg+QS-21 n=22 Participants Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	ACC 10 μg+QS-21 n=20 Participants Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Overall ACC + QS21 n=42 Participants Participants received either 3 μg of ACC-001 and 50 μg of QS-21 or 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Placebo n=21 Participants Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Change From Baseline in Volumetric Brain MRI Measurements in Hippocampal Boundary Shift Integral (HBSI), Total Week 10 (N: 22, 20, 42, 20)	-0.056 mL Interval -0.097 to -0.015	-0.016 mL Interval -0.059 to 0.027	-0.036 mL Interval -0.066 to -0.006	-0.041 mL Interval -0.084 to 0.002
Change From Baseline in Volumetric Brain MRI Measurements in Hippocampal Boundary Shift Integral (HBSI), Total Week 24 (N: 22, 20, 42, 21)	-0.124 mL Interval -0.167 to -0.081	-0.065 mL Interval -0.11 to -0.02	-0.094 mL Interval -0.126 to -0.063	-0.099 mL Interval -0.143 to -0.055
Change From Baseline in Volumetric Brain MRI Measurements in Hippocampal Boundary Shift Integral (HBSI), Total Week 50 (N: 22, 19, 41, 18)	-0.251 mL Interval -0.316 to -0.187	-0.159 mL Interval -0.228 to -0.09	-0.205 mL Interval -0.252 to -0.158	-0.226 mL Interval -0.295 to -0.157
Change From Baseline in Volumetric Brain MRI Measurements in Hippocampal Boundary Shift Integral (HBSI), Total Week 76 (N: 22, 17, 39, 16)	-0.357 mL Interval -0.46 to -0.253	-0.255 mL Interval -0.368 to -0.142	-0.306 mL Interval -0.383 to -0.229	-0.334 mL Interval -0.448 to -0.219
Change From Baseline in Volumetric Brain MRI Measurements in Hippocampal Boundary Shift Integral (HBSI), Total Week 104 (N: 18, 16, 34, 14)	-0.468 mL Interval -0.601 to -0.335	-0.329 mL Interval -0.472 to -0.185	-0.398 mL Interval -0.496 to -0.301	-0.471 mL Interval -0.62 to -0.323

OTHER_PRE_SPECIFIED outcome

Timeframe: 104 weeks

Population: FAS population included all randomized participants who had at least one dose of investigational product.

Left HBSI measures the left hippocampal atrophy from registered MRI scan pairs, by subtracting the corresponding area under the intensity profile across a boundary in the repeat scans.

Outcome measures

Measure	ACC 3 μg+QS-21 n=22 Participants Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	ACC 10 μg+QS-21 n=20 Participants Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Overall ACC + QS21 n=42 Participants Participants received either 3 μg of ACC-001 and 50 μg of QS-21 or 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Placebo n=21 Participants Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Left Week 10 (N: 22, 20, 42, 20)	-0.029 mL Interval -0.051 to -0.007	-0.010 mL Interval -0.034 to 0.014	-0.020 mL Interval -0.036 to -0.003	-0.019 mL Interval -0.042 to 0.005
Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Left Week 24 (N: 22, 20, 42, 21)	-0.057 mL Interval -0.081 to -0.034	-0.037 mL Interval -0.062 to -0.012	-0.047 mL Interval -0.064 to -0.03	-0.040 mL Interval -0.064 to -0.015
Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Left Week 50 (N: 22, 19, 41, 18)	-0.119 mL Interval -0.152 to -0.086	-0.080 mL Interval -0.115 to -0.045	-0.099 mL Interval -0.124 to -0.075	-0.107 mL Interval -0.142 to -0.072
Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Left Week 76 (N: 22, 17, 39, 16)	-0.163 mL Interval -0.213 to -0.114	-0.117 mL Interval -0.171 to -0.064	-0.140 mL Interval -0.177 to -0.104	-0.157 mL Interval -0.211 to -0.102
Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Left Week 104 (N: 18, 16, 34, 14)	-0.222 mL Interval -0.288 to -0.155	-0.158 mL Interval -0.23 to -0.086	-0.190 mL Interval -0.239 to -0.14	-0.230 mL Interval -0.305 to -0.155

OTHER_PRE_SPECIFIED outcome

Timeframe: 104 weeks

Population: FAS population included all randomized participants who had at least one dose of investigational product.

Right HBSI measures the right hippocampal atrophy from registered MRI scan pairs, by subtracting the corresponding area under the intensity profile across a boundary in the repeat scans.

Outcome measures

Measure	ACC 3 μg+QS-21 n=22 Participants Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	ACC 10 μg+QS-21 n=20 Participants Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Overall ACC + QS21 n=42 Participants Participants received either 3 μg of ACC-001 and 50 μg of QS-21 or 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Placebo n=21 Participants Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Right Week 104 (N: 18, 16, 34, 14)	-0.247 mL Interval -0.318 to -0.175	-0.170 mL Interval -0.247 to -0.093	-0.208 mL Interval -0.261 to -0.156	-0.240 mL Interval -0.32 to -0.161
Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Right Week 10 (N: 22, 20, 42, 20)	-0.027 mL Interval -0.051 to -0.004	-0.005 mL Interval -0.03 to 0.02	-0.016 mL Interval -0.033 to 0.001	-0.021 mL Interval -0.046 to 0.003
Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Right Week 24 (N: 22, 20, 42, 21)	-0.067 mL Interval -0.091 to -0.044	-0.027 mL Interval -0.052 to -0.002	-0.047 mL Interval -0.064 to -0.03	-0.059 mL Interval -0.084 to -0.035
Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Right Week 50 (N: 22, 19, 41, 18)	-0.133 mL Interval -0.168 to -0.098	-0.078 mL Interval -0.116 to -0.041	-0.106 mL Interval -0.132 to -0.08	-0.119 mL Interval -0.157 to -0.081
Change From Baseline in Volumetric Brain MRI Measurements in HBSI, Right Week 76 (N: 22, 17, 39, 16)	-0.194 mL Interval -0.252 to -0.135	-0.136 mL Interval -0.199 to -0.072	-0.165 mL Interval -0.208 to -0.121	-0.177 mL Interval -0.242 to -0.113

OTHER_PRE_SPECIFIED outcome

Timeframe: 104 weeks

Population: FAS population included all randomized participants who had at least one dose of investigational product.

The NTB evaluated cognitive domains that are known to be affected early in the course of Alzheimer's disease (AD). The cognitive tests included in the NTB were: Rey Auditory Verbal Learning Test - Immediate recall, Detection, Identification, Go-No-Go Task, One Back Task, Controlled Oral Word Association Test, Category Fluency Test, and Rey Auditory Verbal Learning Test - delayed recall and recognition. For each of the eight NTB components, an individual z-score was derived based on the primary raw score of each test. Based on the individual z-scores, a composite z-score was derived using the formula: (z1-z2-z3-z4+z5+z6+z7+z8)/8. Positive change indicating an improvement from baseline.

Outcome measures

Measure	ACC 3 μg+QS-21 n=22 Participants Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	ACC 10 μg+QS-21 n=20 Participants Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Overall ACC + QS21 n=42 Participants Participants received either 3 μg of ACC-001 and 50 μg of QS-21 or 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Placebo n=21 Participants Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Change From Baseline in Neuropsychological Test Battery (NTB) Week 26 (N: 20, 20, 40, 19)	-0.14 z-scores Interval -0.28 to 0.0	-0.07 z-scores Interval -0.21 to 0.08	-0.10 z-scores Interval -0.2 to 0.0	-0.11 z-scores Interval -0.25 to 0.04
Change From Baseline in Neuropsychological Test Battery (NTB) Week 52 (N: 22, 19, 41, 20)	-0.08 z-scores Interval -0.26 to 0.09	-0.08 z-scores Interval -0.27 to 0.11	-0.08 z-scores Interval -0.21 to 0.05	-0.06 z-scores Interval -0.25 to 0.12
Change From Baseline in Neuropsychological Test Battery (NTB) Week 78 (N: 22, 18, 40, 18)	-0.31 z-scores Interval -0.52 to -0.1	0.01 z-scores Interval -0.22 to 0.23	-0.15 z-scores Interval -0.31 to 0.0	-0.27 z-scores Interval -0.5 to -0.04
Change From Baseline in Neuropsychological Test Battery (NTB) Week 104 (N: 18, 18, 36, 15)	-0.42 z-scores Interval -0.71 to -0.14	-0.12 z-scores Interval -0.42 to 0.18	-0.27 z-scores Interval -0.48 to -0.06	-0.45 z-scores Interval -0.76 to -0.14

OTHER_PRE_SPECIFIED outcome

Timeframe: 104 weeks

Population: FAS population included all randomized participants who had at least one dose of investigational product.

FAQ is a 10-item, caregiver-based questionnaire and was administered to the study partner who was asked to rate the participant's ability to perform a variety of activities ranging from shopping, doing the laundry, simple financial transactions, comprehension of current events, some recreational or avocational activities, and reading. FAQ total score was calculated by adding the scores from each of the 10 items. A negative change indicated an improvement from baseline. FAQ Total Score is the sum of 10 items, ranging from 0 (best possible outcome) to 100 (worst possible outcome).

Outcome measures

Measure	ACC 3 μg+QS-21 n=22 Participants Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	ACC 10 μg+QS-21 n=20 Participants Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Overall ACC + QS21 n=42 Participants Participants received either 3 μg of ACC-001 and 50 μg of QS-21 or 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Placebo n=21 Participants Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Change From Baseline in Functional Activities Questionnaire (FAQ) Total Score Week 26 (N: 22, 20, 42, 19)	3.45 score Interval 1.89 to 5.02	0.25 score Interval -1.44 to 1.94	1.85 score Interval 0.68 to 3.03	1.80 score Interval 0.02 to 3.58
Change From Baseline in Functional Activities Questionnaire (FAQ) Total Score Week 52 (N: 22, 19, 41, 19)	4.63 score Interval 2.71 to 6.55	0.98 score Interval -1.1 to 3.06	2.81 score Interval 1.37 to 4.24	2.85 score Interval 0.71 to 4.99
Change From Baseline in Functional Activities Questionnaire (FAQ) Total Score Week 78 (N: 22, 18, 40, 17)	5.36 score Interval 3.03 to 7.69	2.09 score Interval -0.45 to 4.64	3.73 score Interval 1.99 to 5.47	4.89 score Interval 2.26 to 7.51
Change From Baseline in Functional Activities Questionnaire (FAQ) Total Score Week 104 (N: 18, 18, 36, 14)	6.90 score Interval 4.25 to 9.55	3.11 score Interval 0.33 to 5.89	5.01 score Interval 3.07 to 6.94	4.66 score Interval 1.66 to 7.66

OTHER_PRE_SPECIFIED outcome

Timeframe: 104 weeks

Population: FAS population included all randomized participants who had at least one dose of investigational product.

Clinical Dementia Rating (CDR) is a global clinical staging instrument that was administrated by a trained rater to assess a participant's level of impairment in six domains including: Memory, Orientation, Judgement and Problem Solving, Community Affairs, Home and Hobbies, and Personal Care, based on the CDR interview. The CDR included discussions with the participant and study partner using a structured format. A CDR-SOB score was derived based on individual scores from the six domains. A negative change indicated an improvement from baseline. The total CDR-SB score is calculated as the sum of the six clinical ratings. The CDR-SOB score range for each domain is 0 to 3. The CDR-SOB total score ranges from 0 to 18, with higher scores indicating greater dementia. If any individual item is missing, then the CDR-SB is set to missing.

Outcome measures

Measure	ACC 3 μg+QS-21 n=22 Participants Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	ACC 10 μg+QS-21 n=20 Participants Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Overall ACC + QS21 n=42 Participants Participants received either 3 μg of ACC-001 and 50 μg of QS-21 or 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Placebo n=21 Participants Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SOB) Week 104 (N: 17, 18, 35, 14)	2.15 score Interval 1.32 to 2.97	1.23 score Interval 0.37 to 2.1	1.69 score Interval 1.09 to 2.29	1.11 score Interval 0.23 to 2.0
Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SOB) Week 26 (N: 22, 20, 42, 20)	0.60 score Interval 0.2 to 1.0	0.31 score Interval -0.11 to 0.73	0.46 score Interval 0.16 to 0.75	0.21 score Interval -0.22 to 0.63
Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SOB) Week 52 (N: 22, 19, 41, 20)	1.10 score Interval 0.53 to 1.66	0.39 score Interval -0.21 to 0.99	0.74 score Interval 0.33 to 1.16	0.71 score Interval 0.11 to 1.31
Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SOB) Week 78 (N: 22, 18, 40, 18)	1.71 score Interval 1.04 to 2.39	0.69 score Interval -0.04 to 1.41	1.20 score Interval 0.7 to 1.7	1.25 score Interval 0.53 to 1.97

OTHER_PRE_SPECIFIED outcome

Timeframe: 104 weeks

Population: FAS population included all randomized participants who had at least one dose of investigational product.

The NPI scale assesses 12 domains (delusions, hallucinations, agitation, depression, anxiety, euphoria, apathy, disinhibition, irritability, aberrant motor behavior, nighttime behavior, and appetite and eating changes). The symptoms were rated on the basis of questions administered to the study partner. If a preliminary question for each domain was answered as 'Yes', each domain was rated on a 4-point frequency scale and on a 3-point severity scale. If the preliminary question was answered as 'No', the frequency, severity, and distress scales were set to zero. A negative change indicated an improvement from baseline. For each of the 12 domains, a sub-scale score is calculated as frequency*severity and ranges from 0 to 12. The NPI total score is then calculated by summing the scores of the 12 sub-scale scores. The NPI total scores ranges from 0 to 144 with higher scores indicating greater behavioral impairment. The caregiver distress score is not included in the NPI total score.

Outcome measures

Measure	ACC 3 μg+QS-21 n=22 Participants Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	ACC 10 μg+QS-21 n=20 Participants Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Overall ACC + QS21 n=42 Participants Participants received either 3 μg of ACC-001 and 50 μg of QS-21 or 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Placebo n=21 Participants Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score Week 26 (N: 22, 20, 42, 20)	1.51 score Interval -0.5 to 3.52	-0.76 score Interval -2.87 to 1.35	0.38 score Interval -1.09 to 1.84	3.50 score Interval 1.37 to 5.64
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score Week 52 (N: 22, 19, 41, 20)	1.97 score Interval -0.31 to 4.25	2.44 score Interval 0.0 to 4.89	2.21 score Interval 0.52 to 3.89	2.65 score Interval 0.24 to 5.06
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score Week 78 (N: 22, 18, 40, 18)	2.01 score Interval -0.15 to 4.18	1.17 score Interval -1.19 to 3.53	1.59 score Interval -0.02 to 320.0	3.34 score Interval 0.97 to 5.71
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score Week 104 (N: 18, 18, 36, 15)	1.38 score Interval -0.53 to 3.29	1.31 score Interval -0.61 to 3.22	1.34 score Interval -0.03 to 2.71	2.08 score Interval -0.03 to 4.19

OTHER_PRE_SPECIFIED outcome

Timeframe: 104 weeks

Population: FAS population included all randomized participants who had at least one dose of investigational product.

The NPI scale assesses 12 domains (delusions, hallucinations, agitation, depression, anxiety, euphoria, apathy, disinhibition, irritability, aberrant motor behavior, nighttime behavior, and appetite and eating changes). The symptoms were rated on the basis of questions administered to the study partner. For each domain, the study partner also rated his/her own 'emotional or psychological' distress caused by the participant's behavior on a 6-point scale. The study partner NPI-D total score was calculated by summing the scores of the 12 sub-scale distress scores. A negative change indicated an improvement from baseline. The caregiver distress (NPI-D) total score is calculated by summing the scores of the 12 sub-scale distress scores. The NPI-D total scores ranges from 0 to 60 with higher scores indicating greater distress.

Outcome measures

Measure	ACC 3 μg+QS-21 n=22 Participants Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	ACC 10 μg+QS-21 n=20 Participants Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Overall ACC + QS21 n=42 Participants Participants received either 3 μg of ACC-001 and 50 μg of QS-21 or 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Placebo n=21 Participants Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Change From Baseline in NPI Distress Score (NPI-D) Week 26 (N: 22, 20, 42, 20)	1.49 score Interval 0.11 to 2.87	0.42 score Interval -1.03 to 1.86	0.95 score Interval -0.05 to 1.96	1.57 score Interval 0.1 to 3.05
Change From Baseline in NPI Distress Score (NPI-D) Week 52 (N: 22, 19, 41, 20)	1.54 score Interval 0.2 to 2.88	1.24 score Interval -0.2 to 2.68	1.39 score Interval 0.39 to 2.38	2.27 score Interval 0.84 to 3.71
Change From Baseline in NPI Distress Score (NPI-D) Week 78 (N: 22, 18, 40, 18)	1.45 score Interval 0.11 to 2.79	0.44 score Interval -1.01 to 1.9	0.95 score Interval -0.05 to 1.94	2.56 score Interval 1.08 to 4.03
Change From Baseline in NPI Distress Score (NPI-D) Week 104 (N: 18, 18, 36, 15)	1.73 score Interval 0.02 to 3.44	1.76 score Interval 0.03 to 3.48	1.74 score Interval 0.52 to 2.97	1.27 score Interval -0.62 to 3.16

OTHER_PRE_SPECIFIED outcome

Timeframe: 104 weeks

Population: FAS population included all randomized participants who had at least one dose of investigational product.

The MMSE is a brief, structured examination of cognitive function consisting of the 11 item: Orientation-What, Orientation-Where, Registration-Objects, Attention and Calculation, Recall, Language-Naming, Language-Repetition, Language-Comprehension, Language-Reading, Language-Writing, and Language- Drawing. MMSE total score was the sum of the 11 item scores and it ranges from 0 to 30 with higher score indicating greater cognitive functioning. If any individual item is missing, then the MMSE total score is set to missing. A positive change indicating an improvement from baseline.

Outcome measures

Measure	ACC 3 μg+QS-21 n=22 Participants Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	ACC 10 μg+QS-21 n=20 Participants Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Overall ACC + QS21 n=42 Participants Participants received either 3 μg of ACC-001 and 50 μg of QS-21 or 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Placebo n=21 Participants Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Change From Baseline in Mini Mental State Examination (MMSE) Total Score Week 26 (N: 22, 20, 42, 20)	-1.06 score Interval -2.2 to 0.09	-1.09 score Interval -2.28 to 0.09	-1.08 score Interval -1.9 to -0.25	-1.10 score Interval -2.29 to 0.09
Change From Baseline in Mini Mental State Examination (MMSE) Total Score Week 52 (N: 22, 19, 41, 20)	-2.46 score Interval -3.72 to -1.21	-1.54 score Interval -2.87 to -0.2	-2.00 score Interval -2.92 to -1.08	-1.30 score Interval -2.62 to -0.01
Change From Baseline in Mini Mental State Examination (MMSE) Total Score Week 78 (N: 22, 18, 40, 18)	-2.28 score Interval -3.75 to -0.82	-1.92 score Interval -3.48 to -0.35	-2.10 score Interval -3.17 to -1.03	-1.42 score Interval -2.97 to -0.13
Change From Baseline in Mini Mental State Examination (MMSE) Total Score Week 104 (N: 19, 18, 37, 15)	-3.55 score Interval -5.48 to -1.63	-1.34 score Interval -3.37 to 0.68	-2.45 score Interval -3.85 to -1.05	-2.53 score Interval -4.62 to -0.44

OTHER_PRE_SPECIFIED outcome

Timeframe: 104 weeks

Population: FAS population included all randomized participants who had at least one dose of investigational product.

The ADAS-Cog is a global cognitive measure. For the following 13 items, the participants were rated: Word Recall, Commands, Construction Praxis, Delayed Word Recall Task, Naming Task, Ideational Praxis, Orientation, Word Recognition Task, Remembering Test Instructions, Spoken Language Ability, Word-Finding Difficulty in Spontaneous Speech, Comprehension, and Number Cancellation. The ADAS-cog is a structured scale that evaluates memory, orientation, attention, reasoning, language and constructional praxis. The total score was the sum of the scores from the 13 individual items. This study used a modified 85 point scale with a scoring range of 0 to 85 (13 items). Higher scores of the 13 individual items indicated greater cognitive impairment.

Outcome measures

Measure	ACC 3 μg+QS-21 n=22 Participants Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	ACC 10 μg+QS-21 n=20 Participants Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Overall ACC + QS21 n=42 Participants Participants received either 3 μg of ACC-001 and 50 μg of QS-21 or 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Placebo n=21 Participants Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Change From Baseline in 13-item Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog) Total Score Week 54 (N: 22, 19, 41, 29)	-5.58 score Interval -7.55 to -3.61	-6.69 score Interval -8.83 to -4.55	-6.14 score Interval -7.61 to -4.67	-5.05 score Interval -7.21 to -2.9
Change From Baseline in 13-item Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog) Total Score Week 86 (N: 19, 18, 37, 17)	1.80 score Interval -0.04 to 3.65	0.28 score Interval -1.65 to 2.22	1.04 score Interval -0.31 to 2.39	1.56 score Interval -0.43 to 3.55

OTHER_PRE_SPECIFIED outcome

Timeframe: 104 weeks

Population: FAS population included all randomized participants who had at least one dose of investigational product.

An abbreviated administration (first 6 items) of the DS was used in this study. The DS is a brief study partner-completed measure which assesses the degree of support required by a subject with AD. Since the goal of treatment was to delay or arrest the processes leading to increased dependence, the DS represented a meaningful endpoint for clinical studies in AD. The dependence score was derived by summing the first 6 items of the DS. Item 1 and 2 ranged from 0 - 2 and item 3 - 6 ranged from 0 - 1. The total score was calculated by summing the score from each of the 6 items. So the total score could range from 0 - 8, with higher scores indicating greater dependence.

Outcome measures

Measure	ACC 3 μg+QS-21 n=22 Participants Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	ACC 10 μg+QS-21 n=20 Participants Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Overall ACC + QS21 n=21 Participants Participants received either 3 μg of ACC-001 and 50 μg of QS-21 or 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Placebo Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Change From Baseline in Dependence Scale (DS) Score Week 26 (N: 22, 20 , 20)	0.1 score Standard Deviation 1.44 • Interval 0.2 to 1.0	-0.4 score Standard Deviation 1.39 • Interval -0.11 to 0.73	0.0 score Standard Deviation 1.65 • Interval -0.22 to 0.63	—
Change From Baseline in Dependence Scale (DS) Score Week 52 (N: 22, 19 , 20)	-0.2 score Standard Deviation 1.60 • Interval 0.53 to 1.66	0.2 score Standard Deviation 1.96 • Interval -0.21 to 0.99	0.1 score Standard Deviation 1.86 • Interval 0.11 to 1.31	—
Change From Baseline in Dependence Scale (DS) Score Week 78 (22, 18, 18)	0.2 score Standard Deviation 1.07 • Interval 1.04 to 2.39	0.3 score Standard Deviation 1.41 • Interval -0.04 to 1.41	-0.2 score Standard Deviation 1.93 • Interval 0.53 to 1.97	—
Change From Baseline in Dependence Scale (DS) Score Week 104 (N: 18, 18,15)	0.9 score Standard Deviation 2.21 • Interval 1.32 to 2.97	0.6 score Standard Deviation 1.58 • Interval 0.37 to 2.1	-0.1 score Standard Deviation 2.07 • Interval 0.23 to 2.0	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 104 weeks

Population: FAS population included all randomized participants who had at least one dose of investigational product.

An abbreviated administration of the RUD (RUD-Lite) was used. The RUD-Lite is a comprehensive tool for addressing the magnitude and nature of study partner/caregiver effort in cases of dementia. Since a significant portion of care in Alzheimer's related-dementia was performed informally by the participant's friends or family, it was desirable to measure the extent of this care for use in economic evaluations of disease. The total time spent by the primary caregiver providing support on activities of daily living (ADL), instrumental activities of daily living (IADL) and supervising, respectively, was calculated in two components. Total number of days spent during the past month on each of ADL, IADL, and supervising; and: time per day during the past month on each of ADL, IADL and supervising. The total Primary Caregiver Time per month could range from 0 - 720. This was calculated by multiplying the number of days per month (30) by the number of hours per day (24).

Outcome measures

Measure	ACC 3 μg+QS-21 n=22 Participants Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	ACC 10 μg+QS-21 n=20 Participants Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Overall ACC + QS21 n=21 Participants Participants received either 3 μg of ACC-001 and 50 μg of QS-21 or 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Placebo Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Change From Baseline in Resource Utilization in Dementia (RUD) (Abbreviated) (RUD-Lite) - Primary Caregiver Week 26 (N: 22, 20, 20)	3.97 hours Interval -7.02 to 14.97	-6.05 hours Interval -17.57 to 5.47	6.47 hours Interval -5.23 to 18.17	—
Change From Baseline in Resource Utilization in Dementia (RUD) (Abbreviated) (RUD-Lite) - Primary Caregiver Week 52 (N: 22, 19, 20)	16.76 hours Interval 0.6 to 32.93	-7.97 hours Interval -25.41 to 9.47	21.73 hours Interval 4.66 to 38.79	—
Change From Baseline in Resource Utilization in Dementia (RUD) (Abbreviated) (RUD-Lite) - Primary Caregiver Week 78 (N: 22, 18, 18)	30.80 hours Interval -10.69 to 72.29	-3.23 hours Interval -49.0 to 42.54	61.74 hours Interval 15.98 to 107.51	—
Change From Baseline in Resource Utilization in Dementia (RUD) (Abbreviated) (RUD-Lite) - Primary Caregiver Week 104 (N: 18, 18, 15)	36.36 hours Interval 15.37 to 57.34	-5.88 hours Interval -27.65 to 15.88	20.31 hours Interval -2.29 to 42.92	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 104 weeks

Population: FAS population included all randomized participants who had at least one dose of investigational product.

An abbreviated administration of the RUD (RUD-Lite) was used. The RUD-Lite is a comprehensive tool for addressing the magnitude and nature of study partner/caregiver effort in cases of dementia. Since a significant portion of care in Alzheimer's related-dementia was performed informally by the participant's friends or family, it was desirable to measure the extent of this care for use in economic evaluations of disease. The total time spent by the other caregivers providing support on ADL, IADL and supervising, respectively, was calculated in two components. Total number of days spent during the past month on each of ADL, IADL and supervising; and: time per day during the past month on each of ADL, IADL, and supervising. The total Other Caregiver Time per month could range from 0 - 720. This was calculated by multiplying the number of days per month (30) by the number of hours per day (24).

Outcome measures

Measure	ACC 3 μg+QS-21 n=22 Participants Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	ACC 10 μg+QS-21 n=20 Participants Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Overall ACC + QS21 n=21 Participants Participants received either 3 μg of ACC-001 and 50 μg of QS-21 or 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Placebo Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Change From Baseline in RUD (Abbreviated) (RUD-Lite) - Other Caregivers Week 26 (N: 22, 20, 20)	0.14 hours Interval -4.36 to 4.64	4.03 hours Interval -0.69 to 8.76	1.56 hours Interval -3.17 to 6.28	—
Change From Baseline in RUD (Abbreviated) (RUD-Lite) - Other Caregivers Week 52 (N: 22, 19, 20)	0.72 hours Interval -2.66 to 4.1	3.03 hours Interval -0.52 to 6.59	0.01 hours Interval -3.54 to 3.55	—
Change From Baseline in RUD (Abbreviated) (RUD-Lite) - Other Caregivers Week 78 (N: 22, 18, 18)	0.86 hours Interval -0.36 to 2.08	0.79 hours Interval -0.51 to 2.1	0.06 hours Interval -1.25 to 1.36	—
Change From Baseline in RUD (Abbreviated) (RUD-Lite) - Other Caregivers Week 104 (N: 18, 18, 15)	2.13 hours Interval -9.2 to 13.47	1.58 hours Interval -10.12 to 13.27	9.64 hours Interval -2.67 to 21.96	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 104 weeks

Population: FAS population included all randomized participants who had at least one dose of investigational product.

CDR is a global clinical staging instrument that was administrated by a trained rater to assess a participant's level of impairment in six domains including: Memory, Orientation, Judgement and Problem Solving, Community Affairs, Home and Hobbies, and Personal Care, based on the CDR interview. The CDR included discussions with the participant and study partner using a structured format. CDR global score was derived from the six domains according to a complex algorithm with emphasis on the Memory Domain score. Global CDR score = 0.5 with memory box score of 0.5. The total CDR-SB score is calculated as the sum of the six clinical ratings. The CDR-SOB score range for each domain is 0 to 3, with higher score indicating no significant function. If any individual item is missing, then the CDR-SB is set to missing.

Outcome measures

Measure	ACC 3 μg+QS-21 n=22 Participants Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	ACC 10 μg+QS-21 n=20 Participants Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Overall ACC + QS21 n=42 Participants Participants received either 3 μg of ACC-001 and 50 μg of QS-21 or 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Placebo n=21 Participants Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Percentage of Participants With a Global CDR Score of Equal to or Greater Than 1 for the First Time Week 26	86.4 percentage of participants	70.0 percentage of participants	78.6 percentage of participants	80.0 percentage of participants
Percentage of Participants With a Global CDR Score of Equal to or Greater Than 1 for the First Time Week 52	0.0 percentage of participants	15.0 percentage of participants	7.1 percentage of participants	10.0 percentage of participants
Percentage of Participants With a Global CDR Score of Equal to or Greater Than 1 for the First Time Week 78	13.6 percentage of participants	0.0 percentage of participants	7.1 percentage of participants	0.0 percentage of participants
Percentage of Participants With a Global CDR Score of Equal to or Greater Than 1 for the First Time Week 104	0.0 percentage of participants	10.0 percentage of participants	4.8 percentage of participants	0.0 percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 104 weeks

Population: FAS population included all randomized participants who had at least one dose of investigational product.

Site personnel collecting the samples for anti-Aβ antibody titers were blinded to the participant treatment group assignment. The lower limit of quantification (LLOQ) determined for this assay was 100 U/mL. For any anti-Aβ IgG antibody level that was below the LLOQ (100 U/mL), the lower limit of detection (LLOD) defined as 0.5*LLOQ was imputed.

Outcome measures

Measure	ACC 3 μg+QS-21 n=22 Participants Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	ACC 10 μg+QS-21 n=20 Participants Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Overall ACC + QS21 n=42 Participants Participants received either 3 μg of ACC-001 and 50 μg of QS-21 or 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Placebo n=21 Participants Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers Baseline (N: 21, 18, 39, 21)	50.0 U/ml Interval 50.0 to 50.0	50.0 U/ml Interval 50.0 to 50.0	50.0 U/ml Interval 50.0 to 50.0	53.5 U/ml Interval 46.5 to 61.6
Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers Week 2 (N: 20, 20, 40, 21)	61.5 U/ml Interval 48.5 to 78.0	81.4 U/ml Interval 53.3 to 124.2	70.7 U/ml Interval 55.9 to 89.6	50.0 U/ml Interval 50.0 to 50.0
Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers Week 4 (N: 21, 17, 38, 21)	59.0 U/ml Interval 50.3 to 69.3	86.3 U/ml Interval 53.3 to 139.8	70.0 U/ml Interval 55.7 to 87.9	50.0 U/ml Interval 50.0 to 50.0
Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers Week 6 (N: 22, 20, 42, 21)	1490.0 U/ml Interval 577.0 to 3847.9	1485.3 U/ml Interval 570.0 to 3870.0	1487.7 U/ml Interval 780.5 to 2835.9	50.0 U/ml Interval 50.0 to 50.0
Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers Week 10 (N:22, 20, 42, 20)	774.8 U/ml Interval 355.7 to 1687.7	960.3 U/ml Interval 453.5 to 2033.2	858.1 U/ml Interval 510.3 to 1443.1	50.0 U/ml Interval 50.0 to 50.0
Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers Week 12 (N: 22, 18, 40, 20)	566.4 U/ml Interval 270.5 to 1186.1	536.0 U/ml Interval 238.7 to 1204.0	552.5 U/ml Interval 328.2 to 930.1	50.0 U/ml Interval 50.0 to 50.0
Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers Week 14 (N: 22, 20, 42, 20)	5997.5 U/ml Interval 3541.6 to 10156.5	2796.3 U/ml Interval 1414.2 to 5529.1	4170.3 U/ml Interval 2727.9 to 6375.2	50.0 U/ml Interval 50.0 to 50.0
Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers Week 20 (N: 21, 20, 41, 21)	3320.9 U/ml Interval 1855.9 to 5942.4	2172.9 U/ml Interval 1106.7 to 4266.3	2700.2 U/ml Interval 1757.7 to 4148.2	50.0 U/ml Interval 50.0 to 50.0
Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers Week 26 (N: 22, 19, 41, 20)	1657.0 U/ml Interval 967.3 to 2838.5	1739.1 U/ml Interval 801.9 to 3771.7	1694.6 U/ml Interval 1092.4 to 2628.8	60.7 U/ml Interval 40.5 to 90.9
Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers Week 28 (N: 22, 20, 42, 20)	6482.5 U/ml Interval 4247.1 to 9894.5	4668.3 U/ml Interval 2371.1 to 9190.7	5544.3 U/ml Interval 3802.5 to 8083.7	50.0 U/ml Interval 50.0 to 50.0
Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers Week 34 (N: 22, 20, 42, 20)	3731.9 U/ml Interval 2375.7 to 5862.5	5329.0 U/ml Interval 2754.6 to 10309.3	4421.9 U/ml Interval 3024.7 to 6464.5	50.0 U/ml Interval 50.0 to 50.0
Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers Week 52 (N: 20, 18, 38, 19)	1322.6 U/ml Interval 800.2 to 2185.9	1920.8 U/ml Interval 983.0 to 3753.2	1578.3 U/ml Interval 1060.8 to 2348.2	50.0 U/ml Interval 50.0 to 50.0
Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers Week 54 (N: 20, 19, 39, 19)	6787.7 U/ml Interval 4892.4 to 9417.2	12064.7 U/ml Interval 6642.8 to 21912.2	8982.9 U/ml Interval 6438.2 to 12533.3	50.0 U/ml Interval 50.0 to 50.0
Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers Week 60 (N: 21, 19, 40, 19)	4130.7 U/ml Interval 2948.4 to 5787.2	9665.3 U/ml Interval 5448.3 to 17146.1	6185.7 U/ml Interval 4410.2 to 8676.0	50.0 U/ml Interval 50.0 to 50.0
Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers Week 78 (N: 19, 14, 33, 14)	2007.1 U/ml Interval 1357.3 to 2967.9	2973.5 U/ml Interval 1283.4 to 6889.1	2371.3 U/ml Interval 1590.2 to 3536.0	50.0 U/ml Interval 50.0 to 50.0
Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers Week 80 (N: 19, 14, 33, 16)	8006.3 U/ml Interval 4636.8 to 13824.2	11086.8 U/ml Interval 6331.5 to 19413.8	9192.0 U/ml Interval 6303.8 to 13403.4	50.0 U/ml Interval 50.0 to 50.0
Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers Week 86 (N: 15, 17, 32, 14)	6584.2 U/ml Interval 4090.5 to 10598.3	10125.5 U/ml Interval 6528.3 to 15704.9	8275.6 U/ml Interval 6046.9 to 11325.9	50.0 U/ml Interval 50.0 to 50.0
Geometric Mean Anti-Aβ IgG Enzyme-linked Immunosorbent Assay (ELISA) Titers Week 104 (N: 11, 9, 20, 9)	3960.8 U/ml Interval 2704.6 to 5800.7	3513.9 U/ml Interval 1395.3 to 8849.1	3753.1 U/ml Interval 2481.5 to 5676.2	50.0 U/ml Interval 50.0 to 50.0

OTHER_PRE_SPECIFIED outcome

Timeframe: 104 weeks

Population: FAS population included all randomized participants who had at least one dose of investigational product.

Site personnel collecting the samples for anti-Aβ antibody titers were blinded to the participant treatment group assignment. The LLOQ determined for this assay was 50 U/mL. For any anti-Aβ IgM antibody level that was below the LLOQ (50 U/mL), the LLOD defined as 0.5*LLOQ was imputed.

Outcome measures

Measure	ACC 3 μg+QS-21 n=22 Participants Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	ACC 10 μg+QS-21 n=20 Participants Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Overall ACC + QS21 n=42 Participants Participants received either 3 μg of ACC-001 and 50 μg of QS-21 or 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Placebo n=21 Participants Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Geometric Mean Anti-Aβ IgM ELISA Titers Week 28 (N: 22, 20, 42, 20)	1241.6 U/ml Interval 685.5 to 2248.7	1117.1 U/ml Interval 497.8 to 2506.7	1180.6 U/ml Interval 735.7 to 1894.8	31.9 U/ml Interval 25.9 to 39.2
Geometric Mean Anti-Aβ IgM ELISA Titers Week 34 (N: 22, 20, 42, 20)	953.6 U/ml Interval 519.4 to 1750.8	1084.5 U/ml Interval 456.8 to 2574.7	1013.9 U/ml Interval 616.6 to 1667.2	32.0 U/ml Interval 25.9 to 39.5
Geometric Mean Anti-Aβ IgM ELISA Titers Week 10 (N:22, 20, 42, 20)	723.6 U/ml Interval 318.9 to 1641.8	967.3 U/ml Interval 397.4 to 2354.6	830.8 U/ml Interval 465.9 to 1481.5	32.1 U/ml Interval 25.8 to 39.9
Geometric Mean Anti-Aβ IgM ELISA Titers Week 12 (N: 22, 18, 40, 19)	604.2 U/ml Interval 277.5 to 1315.6	611.5 U/ml Interval 255.3 to 1464.6	607.5 U/ml Interval 349.0 to 1057.4	32.6 U/ml Interval 26.1 to 40.6
Geometric Mean Anti-Aβ IgM ELISA Titers Week 14 (N: 22, 20, 42, 20)	1232.4 U/ml Interval 632.4 to 2401.8	1194.6 U/ml Interval 502.6 to 2839.0	1214.2 U/ml Interval 724.5 to 2035.0	32.6 U/ml Interval 26.0 to 40.8
Geometric Mean Anti-Aβ IgM ELISA Titers Week 20 (N: 21, 20, 41, 21)	1060.2 U/ml Interval 505.2 to 2224.8	1070.5 U/ml Interval 456.7 to 2509.4	1065.2 U/ml Interval 622.3 to 1823.3	31.6 U/ml Interval 25.9 to 38.5
Geometric Mean Anti-Aβ IgM ELISA Titers Week 26 (N: 22, 19, 41, 20)	684.8 U/ml Interval 361.8 to 1296.3	939.4 U/ml Interval 414.8 to 2127.4	792.9 U/ml Interval 485.9 to 1293.8	32.6 U/ml Interval 26.1 to 40.9
Geometric Mean Anti-Aβ IgM ELISA Titers Week 60 (N: 21, 19, 40, 19)	782.2 U/ml Interval 409.2 to 1495.2	1228.4 U/ml Interval 471.9 to 3197.6	969.2 U/ml Interval 561.7 to 1672.4	31.0 U/ml Interval 24.9 to 38.7
Geometric Mean Anti-Aβ IgM ELISA Titers Week 78 (N: 19, 14, 33, 14)	635.3 U/ml Interval 306.2 to 1318.2	321.4 U/ml Interval 111.1 to 929.4	475.8 U/ml Interval 263.4 to 859.5	28.5 U/ml Interval 23.5 to 34.5
Geometric Mean Anti-Aβ IgM ELISA Titers Week 104 (N: 11, 9, 20, 9)	602.7 U/ml Interval 221.2 to 1642.1	287.8 U/ml Interval 65.1 to 1271.9	432.2 U/ml Interval 195.1 to 957.3	29.2 U/ml Interval 20.4 to 41.9
Geometric Mean Anti-Aβ IgM ELISA Titers Week 80 (N: 19, 14, 33, 16)	744.8 U/ml Interval 376.0 to 1475.0	677.0 U/ml Interval 213.5 to 2174.2	715.2 U/ml Interval 397.0 to 1288.6	30.7 U/ml Interval 23.9 to 39.3
Geometric Mean Anti-Aβ IgM ELISA Titers Week 86 (N: 15, 17, 32, 14)	768.1 U/ml Interval 278.7 to 2117.0	1023.7 U/ml Interval 361.0 to 2903.0	894.7 U/ml Interval 449.0 to 1782.7	32.2 U/ml Interval 23.7 to 43.7
Geometric Mean Anti-Aβ IgM ELISA Titers Week 52 (N: 20, 18, 38, 19)	493.8 U/ml Interval 269.2 to 905.8	522.9 U/ml Interval 211.7 to 1291.4	507.4 U/ml Interval 305.5 to 842.7	29.2 U/ml Interval 24.3 to 35.0
Geometric Mean Anti-Aβ IgM ELISA Titers Week 54 (N: 20, 19, 39, 19)	776.5 U/ml Interval 426.1 to 1415.0	1176.0 U/ml Interval 495.4 to 2791.3	950.5 U/ml Interval 575.9 to 1568.9	29.8 U/ml Interval 24.2 to 36.6
Geometric Mean Anti-Aβ IgM ELISA Titers Week 4 (N: 21, 17, 38, 21)	75.0 U/ml Interval 41.5 to 135.6	141.3 U/ml Interval 72.8 to 274.0	99.6 U/ml Interval 64.6 to 153.5	31.0 U/ml Interval 25.8 to 37.1
Geometric Mean Anti-Aβ IgM ELISA Titers Week 6 (N: 22, 20, 42, 21)	840.8 U/ml Interval 387.9 to 1822.8	975.8 U/ml Interval 482.0 to 1975.8	902.6 U/ml Interval 545.1 to 1494.5	31.5 U/ml Interval 26.0 to 38.3
Geometric Mean Anti-Aβ IgM ELISA Titers Baseline (N: 21, 18, 39, 21)	31.8 U/ml Interval 25.0 to 40.4	33.9 U/ml Interval 23.6 to 48.8	32.7 U/ml Interval 26.8 to 40.1	31.6 U/ml Interval 26.0 to 38.4
Geometric Mean Anti-Aβ IgM ELISA Titers Week 2 (N: 20, 20, 40, 21)	69.7 U/ml Interval 37.9 to 128.1	121.0 U/ml Interval 66.1 to 221.6	91.8 U/ml Interval 60.4 to 139.6	30.2 U/ml Interval 25.1 to 36.3

OTHER_PRE_SPECIFIED outcome

Timeframe: 104 weeks

Population: FAS population included all randomized participants who had at least one dose of investigational product.

The PDQ is a tool consisting of 20 questions and is designed to assess perceived cognitive deficits from the participant's perspective. The instrument assessed a variety of questions in the following areas: attention/concentration, retrospective memory, prospective memory, and planning/organization. The Attention/Concentration Domain Score is the sum of the raw scores on items 1, 5, 9, 13 and 17, with a range from 0 - 4 for each of the 5 items. So the Attention/Concentration Domain Score could range from 0 - 20, with higher scores indicating greater perceived cognitive impairment.

Outcome measures

Measure	ACC 3 μg+QS-21 n=22 Participants Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	ACC 10 μg+QS-21 n=20 Participants Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Overall ACC + QS21 n=21 Participants Participants received either 3 μg of ACC-001 and 50 μg of QS-21 or 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Placebo Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Change From Baseline in Perceived Deficits Questionnaire (PDQ) - Subject - Attention/Concentration Domain Score Week 26 (N: 22, 20 , 20)	0.5 score Standard Deviation 3.07 • Interval 0.2 to 1.0	0.1 score Standard Deviation 2.95 • Interval -0.11 to 0.73	0.5 score Standard Deviation 3.49 • Interval -0.22 to 0.63	—
Change From Baseline in Perceived Deficits Questionnaire (PDQ) - Subject - Attention/Concentration Domain Score Week 52 (N: 22, 19 , 20)	0.7 score Standard Deviation 2.41 • Interval 0.53 to 1.66	-0.1 score Standard Deviation 2.91 • Interval -0.21 to 0.99	0.7 score Standard Deviation 3.34 • Interval 0.11 to 1.31	—
Change From Baseline in Perceived Deficits Questionnaire (PDQ) - Subject - Attention/Concentration Domain Score Week 78 (N: 22, 18, 18)	0.7 score Standard Deviation 3.27 • Interval 1.04 to 2.39	-0.1 score Standard Deviation 2.83 • Interval -0.04 to 1.41	1.4 score Standard Deviation 3.66 • Interval 0.53 to 1.97	—
Change From Baseline in Perceived Deficits Questionnaire (PDQ) - Subject - Attention/Concentration Domain Score Week 104 (N: 18, 18,15)	1.6 score Standard Deviation 3.54 • Interval 1.32 to 2.97	1.1 score Standard Deviation 3.14 • Interval 0.37 to 2.1	1.3 score Standard Deviation 3.79 • Interval 0.23 to 2.0	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 104 weeks

Population: FAS population included all randomized participants who had at least one dose of investigational product.

The PDQ is a tool consisting of 20 questions and is designed to assess perceived cognitive deficits from the participant's perspective. The instrument assessed a variety of questions in the following areas: attention/concentration, retrospective memory, prospective memory, and planning/organization. The Retrospective Memory Domain Score is the sum of the raw scores on items 2, 6, 10, 14, and 18, with a range from 0 - 4 for each of the 5 items. So the Retrospective Memory Domain Score could range from 0 - 20, with higher scores indicating greater perceived cognitive impairment.

Outcome measures

Measure	ACC 3 μg+QS-21 n=22 Participants Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	ACC 10 μg+QS-21 n=20 Participants Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Overall ACC + QS21 n=21 Participants Participants received either 3 μg of ACC-001 and 50 μg of QS-21 or 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Placebo Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Change From Baseline in PDQ - Subject - Retrospective Memory Domain Score Week 26 (N: 22, 20 , 20)	0.5 score Standard Deviation 3.11 • Interval 0.2 to 1.0	-1.2 score Standard Deviation 2.89 • Interval -0.11 to 0.73	0.4 score Standard Deviation 4.21 • Interval -0.22 to 0.63	—
Change From Baseline in PDQ - Subject - Retrospective Memory Domain Score Week 52 (N: 22, 19 , 20)	0.0 score Standard Deviation 2.82 • Interval 0.53 to 1.66	0.2 score Standard Deviation 2.52 • Interval -0.21 to 0.99	0.5 score Standard Deviation 4.12 • Interval 0.11 to 1.31	—
Change From Baseline in PDQ - Subject - Retrospective Memory Domain Score Week 78 (N: 22, 18, 18)	1.0 score Standard Deviation 3.78 • Interval 1.04 to 2.39	0.1 score Standard Deviation 2.61 • Interval -0.04 to 1.41	1.2 score Standard Deviation 4.14 • Interval 0.53 to 1.97	—
Change From Baseline in PDQ - Subject - Retrospective Memory Domain Score Week 104 (N: 18, 18,15)	1.6 score Standard Deviation 3.47 • Interval 1.32 to 2.97	-0.3 score Standard Deviation 2.59 • Interval 0.37 to 2.1	1.4 score Standard Deviation 5.03 • Interval 0.23 to 2.0	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 104 weeks

Population: FAS population included all randomized participants who had at least one dose of investigational product.

The PDQ is a tool consisting of 20 questions and is designed to assess perceived cognitive deficits from the participant's perspective. The instrument assessed a variety of questions in the following areas: attention/concentration, retrospective memory, prospective memory, and planning/organization. The Prospective Memory Domain Score is the sum of the raw scores on items 3, 7, 11, 15, and 19, with a range from 0 - 4 for each of the 5 items. So the Prospective Memory Domain Score could range from 0 - 20, with higher scores indicating greater perceived cognitive impairment.

Outcome measures

Measure	ACC 3 μg+QS-21 n=22 Participants Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	ACC 10 μg+QS-21 n=20 Participants Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Overall ACC + QS21 n=21 Participants Participants received either 3 μg of ACC-001 and 50 μg of QS-21 or 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Placebo Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Change From Baseline in PDQ - Subject - Prospective Memory Domain Score Week 26 (N: 22, 20 , 20)	0.1 score Standard Deviation 2.65 • Interval 0.2 to 1.0	-0.1 score Standard Deviation 2.17 • Interval -0.11 to 0.73	-0.7 score Standard Deviation 3.48 • Interval -0.22 to 0.63	—
Change From Baseline in PDQ - Subject - Prospective Memory Domain Score Week 52 (N: 22, 19 , 20)	0.4 score Standard Deviation 2.94 • Interval 0.53 to 1.66	0.1 score Standard Deviation 1.73 • Interval -0.21 to 0.99	-0.1 score Standard Deviation 2.70 • Interval 0.11 to 1.31	—
Change From Baseline in PDQ - Subject - Prospective Memory Domain Score Week 78 (N: 22, 18, 18)	0.3 score Standard Deviation 2.51 • Interval 1.04 to 2.39	-0.1 score Standard Deviation 1.43 • Interval -0.04 to 1.41	0.9 score Standard Deviation 2.80 • Interval 0.53 to 1.97	—
Change From Baseline in PDQ - Subject - Prospective Memory Domain Score Week 104 (N: 18, 18,15)	0.5 score Standard Deviation 2.66 • Interval 1.32 to 2.97	0.6 score Standard Deviation 1.94 • Interval 0.37 to 2.1	1.3 score Standard Deviation 3.88 • Interval 0.23 to 2.0	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 104 weeks

Population: FAS population included all randomized participants who had at least one dose of investigational product.

The PDQ is a tool consisting of 20 questions and is designed to assess perceived cognitive deficits from the participant's perspective. The instrument assessed a variety of questions in the following areas: attention/concentration, retrospective memory, prospective memory, and planning/organization. The Planning/Organization Domain Score is the sum of the raw scores on items 4, 8, 12, 16, and 20, with a range from 0 - 4 for each of the 5 items. So the Planning/Organization Domain Score could range from 0 - 20, with higher scores indicating greater perceived cognitive impairment.

Outcome measures

Measure	ACC 3 μg+QS-21 n=22 Participants Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	ACC 10 μg+QS-21 n=20 Participants Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Overall ACC + QS21 n=21 Participants Participants received either 3 μg of ACC-001 and 50 μg of QS-21 or 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Placebo Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Change From Baseline in PDQ - Subject - Planning/Organization Domain Score Week 26 (N: 22, 20 , 20)	0.3 score Standard Deviation 3.39 • Interval 0.2 to 1.0	-0.4 score Standard Deviation 2.08 • Interval -0.11 to 0.73	-0.4 score Standard Deviation 3.05 • Interval -0.22 to 0.63	—
Change From Baseline in PDQ - Subject - Planning/Organization Domain Score Week 52 (N: 22, 19 , 20)	0.3 score Standard Deviation 2.91 • Interval 0.53 to 1.66	-0.1 score Standard Deviation 2.53 • Interval -0.21 to 0.99	0.3 score Standard Deviation 3.26 • Interval 0.11 to 1.31	—
Change From Baseline in PDQ - Subject - Planning/Organization Domain Score Week 78 (N: 22, 18, 18)	1.0 score Standard Deviation 3.73 • Interval 1.04 to 2.39	1.2 score Standard Deviation 1.80 • Interval -0.04 to 1.41	0.9 score Standard Deviation 4.34 • Interval 0.53 to 1.97	—
Change From Baseline in PDQ - Subject - Planning/Organization Domain Score Week 104 (N: 18, 18,15)	1.6 score Standard Deviation 3.35 • Interval 1.32 to 2.97	1.0 score Standard Deviation 2.45 • Interval 0.37 to 2.1	1.3 score Standard Deviation 3.79 • Interval 0.23 to 2.0	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 104 weeks

Population: FAS population included all randomized participants who had at least one dose of investigational product.

The PDQ is a tool consisting of 20 questions and is designed to assess perceived cognitive deficits from the participant's perspective. The instrument assessed a variety of questions in the following areas: attention/concentration, retrospective memory, prospective memory, and planning/organization. The Total Score is computed by adding raw scores for all of the items (or all 4 domain scores) together. It could range from 0 - 80, with higher scores indicating greater perceived cognitive impairment.

Outcome measures

Measure	ACC 3 μg+QS-21 n=22 Participants Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	ACC 10 μg+QS-21 n=20 Participants Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Overall ACC + QS21 n=21 Participants Participants received either 3 μg of ACC-001 and 50 μg of QS-21 or 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Placebo Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Change From Baseline in PDQ - Subject - Total Score Week 26 (N: 22, 20 , 20)	1.4 score Standard Deviation 10.72	-1.6 score Standard Deviation 7.54	-0.3 score Standard Deviation 12.95	—
Change From Baseline in PDQ - Subject - Total Score Week 52 (N: 22, 19 , 20)	1.5 score Standard Deviation 8.60	0.2 score Standard Deviation 7.83	1.5 score Standard Deviation 11.60	—
Change From Baseline in PDQ - Subject - Total Score Week 78 (N: 22, 18, 18)	3.0 score Standard Deviation 11.03	1.2 score Standard Deviation 6.53	4.4 score Standard Deviation 13.74	—
Change From Baseline in PDQ - Subject - Total Score Week 104 (N: 18, 18,15)	5.2 score Standard Deviation 10.76	2.4 score Standard Deviation 8.36	5.3 score Standard Deviation 15.63	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 104 weeks

Population: FAS population included all randomized participants who had at least one dose of investigational product.

The PDQ-R is a tool consisting of 20 questions, is designed to assess perceived cognitive deficits, and was administered to the study partner. The instrument assessed a variety of questions in the following areas: attention/concentration, retrospective memory, prospective memory, and planning/organization. The Attention/Concentration Domain Score is the sum of the raw scores on items 1, 5, 9, 13, and 17, with a range from 0 - 4 for each of the 5 items. So the Attention/Concentration Domain Score could range from 0 - 20, with higher scores indicating greater perceived cognitive impairment.

Outcome measures

Measure	ACC 3 μg+QS-21 n=22 Participants Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	ACC 10 μg+QS-21 n=20 Participants Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Overall ACC + QS21 n=21 Participants Participants received either 3 μg of ACC-001 and 50 μg of QS-21 or 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Placebo Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Change From Baseline in PDQ-R - Relative - Attention/Concentration Domain Score Week 26 (N: 22, 20 , 20)	2.0 score Standard Deviation 3.37 • Interval 0.2 to 1.0	-0.1 score Standard Deviation 3.85 • Interval -0.11 to 0.73	0.9 score Standard Deviation 2.83 • Interval -0.22 to 0.63	—
Change From Baseline in PDQ-R - Relative - Attention/Concentration Domain Score Week 52 (N: 22, 19 , 20)	2.0 score Standard Deviation 3.43 • Interval 0.53 to 1.66	-0.1 score Standard Deviation 3.85 • Interval -0.21 to 0.99	1.8 score Standard Deviation 2.75 • Interval 0.11 to 1.31	—
Change From Baseline in PDQ-R - Relative - Attention/Concentration Domain Score Week 78 (N: 22, 18, 18)	2.9 score Standard Deviation 3.38 • Interval 1.04 to 2.39	0.9 score Standard Deviation 3.77 • Interval -0.04 to 1.41	2.0 score Standard Deviation 3.14 • Interval 0.53 to 1.97	—
Change From Baseline in PDQ-R - Relative - Attention/Concentration Domain Score Week 104 (N: 17, 18,15)	3.9 score Standard Deviation 3.52 • Interval 1.32 to 2.97	1.1 score Standard Deviation 3.16 • Interval 0.37 to 2.1	1.1 score Standard Deviation 4.16 • Interval 0.23 to 2.0	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 104 weeks

Population: FAS population included all randomized participants who had at least one dose of investigational product.

The PDQ-R is a tool consisting of 20 questions, is designed to assess perceived cognitive deficits, and was administered to the study partner. The instrument assessed a variety of questions in the following areas: attention/concentration, retrospective memory, prospective memory, and planning/organization. The Retrospective Memory Domain Score is the sum of the raw scores on items 2, 6, 10, 14, and 18, with a range from 0 - 4 for each of the 5 items. So the Retrospective Memory Domain Score could range from 0 - 20, with higher scores indicating greater perceived cognitive impairment.

Outcome measures

Measure	ACC 3 μg+QS-21 n=22 Participants Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	ACC 10 μg+QS-21 n=20 Participants Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Overall ACC + QS21 n=21 Participants Participants received either 3 μg of ACC-001 and 50 μg of QS-21 or 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Placebo Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Change From Baseline in PDQ-R - Relative - Retrospective Memory Domain Score Week 26 (N: 22, 20 , 20)	1.3 score Standard Deviation 3.49 • Interval 0.2 to 1.0	0.0 score Standard Deviation 2.83 • Interval -0.11 to 0.73	1.8 score Standard Deviation 2.57 • Interval -0.22 to 0.63	—
Change From Baseline in PDQ-R - Relative - Retrospective Memory Domain Score Week 52 (N: 22, 19 , 20)	1.7 score Standard Deviation 2.95 • Interval 0.53 to 1.66	0.4 score Standard Deviation 2.55 • Interval -0.21 to 0.99	1.4 score Standard Deviation 2.41 • Interval 0.11 to 1.31	—
Change From Baseline in PDQ-R - Relative - Retrospective Memory Domain Score Week 78 (N: 22, 18, 18)	2.3 score Standard Deviation 2.55 • Interval 1.04 to 2.39	1.2 score Standard Deviation 2.57 • Interval -0.04 to 1.41	2.2 score Standard Deviation 2.09 • Interval 0.53 to 1.97	—
Change From Baseline in PDQ-R - Relative - Retrospective Memory Domain Score Week 104 (N: 18, 18,15)	3.1 score Standard Deviation 3.03 • Interval 1.32 to 2.97	1.7 score Standard Deviation 2.89 • Interval 0.37 to 2.1	1.7 score Standard Deviation 3.99 • Interval 0.23 to 2.0	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 104 weeks

Population: FAS population included all randomized participants who had at least one dose of investigational product.

The PDQ-R is a tool consisting of 20 questions, is designed to assess perceived cognitive deficits, and was administered to the study partner. The instrument assessed a variety of questions in the following areas: attention/concentration, retrospective memory, prospective memory, and planning/organization. The Prospective Memory Domain Score is the sum of the raw scores on items 3, 7, 11, 15, and 19, with a range from 0 - 4 for each of the 5 items. So the Prospective Memory Domain Score could range from 0 - 20, with higher scores indicating greater perceived cognitive impairment.

Outcome measures

Measure	ACC 3 μg+QS-21 n=22 Participants Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	ACC 10 μg+QS-21 n=20 Participants Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Overall ACC + QS21 n=21 Participants Participants received either 3 μg of ACC-001 and 50 μg of QS-21 or 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Placebo Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Change From Baseline in PDQ-R - Relative - Prospective Memory Domain Score Week 26 (N: 22, 20 , 20)	1.0 score Standard Deviation 2.13 • Interval 0.2 to 1.0	-0.4 score Standard Deviation 2.08 • Interval -0.11 to 0.73	1.1 score Standard Deviation 2.19 • Interval -0.22 to 0.63	—
Change From Baseline in PDQ-R - Relative - Prospective Memory Domain Score Week 52 (N: 22, 19 , 20)	0.6 score Standard Deviation 2.22 • Interval 0.53 to 1.66	0.3 score Standard Deviation 2.51 • Interval -0.21 to 0.99	1.0 score Standard Deviation 2.86 • Interval 0.11 to 1.31	—
Change From Baseline in PDQ-R - Relative - Prospective Memory Domain Score Week 78 (N: 22, 18, 18)	1.5 score Standard Deviation 2.37 • Interval 1.04 to 2.39	0.2 score Standard Deviation 2.53 • Interval -0.04 to 1.41	0.8 score Standard Deviation 2.92 • Interval 0.53 to 1.97	—
Change From Baseline in PDQ-R - Relative - Prospective Memory Domain Score Week 104 (N: 18, 18,15)	2.6 score Standard Deviation 2.48 • Interval 1.32 to 2.97	0.9 score Standard Deviation 2.31 • Interval 0.37 to 2.1	0.5 score Standard Deviation 3.76 • Interval 0.23 to 2.0	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 104 weeks

Population: FAS population included all randomized participants who had at least one dose of investigational product.

The PDQ-R is a tool consisting of 20 questions, is designed to assess perceived cognitive deficits, and was administered to the study partner. The instrument assessed a variety of questions in the following areas: attention/concentration, retrospective memory, prospective memory, and planning/organization. The Planning/Organization Domain Score is the sum of the raw scores on items 4, 8, 12, 16, and 20, with a range from 0 - 4 for each of the 5 items. So the Planning/Organization Domain Score could range from 0 - 20, with higher scores indicating greater perceived cognitive impairment.

Outcome measures

Measure	ACC 3 μg+QS-21 n=22 Participants Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	ACC 10 μg+QS-21 n=20 Participants Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Overall ACC + QS21 n=21 Participants Participants received either 3 μg of ACC-001 and 50 μg of QS-21 or 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Placebo Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Change From Baseline in PDQ-R - Relative - Planning/Organization Domain Score Week 26 (N: 22, 20 , 20)	1.9 score Standard Deviation 3.07 • Interval 0.2 to 1.0	-0.2 score Standard Deviation 2.76 • Interval -0.11 to 0.73	1.7 score Standard Deviation 2.80 • Interval -0.22 to 0.63	—
Change From Baseline in PDQ-R - Relative - Planning/Organization Domain Score Week 52 (N: 22, 19 , 20)	1.7 score Standard Deviation 3.28 • Interval 0.53 to 1.66	0.3 score Standard Deviation 4.27 • Interval -0.21 to 0.99	1.7 score Standard Deviation 2.74 • Interval 0.11 to 1.31	—
Change From Baseline in PDQ-R - Relative - Planning/Organization Domain Score Week 78 (N: 22, 18, 18)	2.5 score Standard Deviation .36 • Interval 1.04 to 2.39	-0.1 score Standard Deviation 3.39 • Interval -0.04 to 1.41	1.9 score Standard Deviation 2.91 • Interval 0.53 to 1.97	—
Change From Baseline in PDQ-R - Relative - Planning/Organization Domain Score Week 104 (N: 18, 18,15)	2.7 score Standard Deviation 3.87 • Interval 1.32 to 2.97	1.1 score Standard Deviation 3.90 • Interval 0.37 to 2.1	1.0 score Standard Deviation 3.63 • Interval 0.23 to 2.0	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 104 weeks

Population: FAS population included all randomized participants who had at least one dose of investigational product.

The PDQ-R is a tool consisting of 20 questions, is designed to assess perceived cognitive deficits, and was administered to the study partner. The instrument assessed a variety of questions in the following areas: attention/concentration, retrospective memory, prospective memory, and planning/organization. The Total Score is computed by adding raw scores for all of the items (or all 4 domain scores) together. It could range from 0 - 80, with higher scores indicating greater perceived cognitive impairment.

Outcome measures

Measure	ACC 3 μg+QS-21 n=22 Participants Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	ACC 10 μg+QS-21 n=20 Participants Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Overall ACC + QS21 n=21 Participants Participants received either 3 μg of ACC-001 and 50 μg of QS-21 or 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Placebo Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Change From Baseline in PDQ-R - Relative - Total Score Week 26 (N: 22, 20 , 20)	6.2 score Standard Deviation 10.69 • Interval 0.2 to 1.0	-0.6 score Standard Deviation 10.37 • Interval -0.11 to 0.73	5.4 score Standard Deviation 8.03 • Interval -0.22 to 0.63	—
Change From Baseline in PDQ-R - Relative - Total Score Week 52 (N: 22, 19 , 20)	6.0 score Standard Deviation 9.91 • Interval 0.53 to 1.66	0.9 score Standard Deviation 11.65 • Interval -0.21 to 0.99	5.7 score Standard Deviation 7.89 • Interval 0.11 to 1.31	—
Change From Baseline in PDQ-R - Relative - Total Score Week 78 (N: 22, 18, 18)	9.2 score Standard Deviation 9.50 • Interval 1.04 to 2.39	2.2 score Standard Deviation 10.30 • Interval -0.04 to 1.41	6.9 score Standard Deviation 8.90 • Interval 0.53 to 1.97	—
Change From Baseline in PDQ-R - Relative - Total Score Week 104 (N: 17, 18,15)	12.8 score Standard Deviation 10.59 • Interval 1.32 to 2.97	4.8 score Standard Deviation 9.98 • Interval 0.37 to 2.1	4.3 score Standard Deviation 13.68 • Interval 0.23 to 2.0	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 104 weeks

Population: FAS population included all randomized participants who had at least one dose of investigational product.

The AD MACQ was administered to the study partner to address preferences for medication administration by assessing: Question a: I would find it easy to give the study medication to the patient myself. Question b: The number of times the medication was given was convenient. Question c: I would prefer to have the study medication given at home by me instead of at the doctor's office by the doctor or nurse. Question d: I would prefer to have the study medication given at home by a nurse instead of at the doctor's office by the doctor or nurse. Question e: Overall, I am satisfied with the way the medication was given.

Outcome measures

Measure	ACC 3 μg+QS-21 n=22 Participants Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	ACC 10 μg+QS-21 n=19 Participants Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Overall ACC + QS21 n=20 Participants Participants received either 3 μg of ACC-001 and 50 μg of QS-21 or 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Placebo Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) Question c: Slightly Agree	13.6 percentage of participants	5.3 percentage of participants	0 percentage of participants	—
Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) Question c: Neither Agree Nor Disagree	22.7 percentage of participants	26.3 percentage of participants	10 percentage of participants	—
Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) Question c: Slightly Disagree	4.5 percentage of participants	0 percentage of participants	10 percentage of participants	—
Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) Question c: Disagree	54.5 percentage of participants	42.1 percentage of participants	60 percentage of participants	—
Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) Question d: Agree	27.3 percentage of participants	21.1 percentage of participants	20 percentage of participants	—
Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) Question d: Slightly Agree	4.5 percentage of participants	10.5 percentage of participants	0 percentage of participants	—
Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) Question d: Neither Agree Nor Disagree	40.9 percentage of participants	31.6 percentage of participants	25 percentage of participants	—
Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) Question a: Agree	40.9 percentage of participants	42.1 percentage of participants	25 percentage of participants	—
Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) Question a: Slightly Agree	13.6 percentage of participants	0 percentage of participants	0 percentage of participants	—
Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) Question a: Neither Agree Nor Disagree	13.6 percentage of participants	21.1 percentage of participants	0 percentage of participants	—
Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) Question a: Slightly Disagree	9.1 percentage of participants	0 percentage of participants	10 percentage of participants	—
Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) Question a: Disagree	22.7 percentage of participants	36.8 percentage of participants	65 percentage of participants	—
Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) Question b: Agree	68.2 percentage of participants	68.4 percentage of participants	70 percentage of participants	—
Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) Question b: Slightly Agree	9.1 percentage of participants	10.5 percentage of participants	15 percentage of participants	—
Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) Question b: Neither Agree Nor Disagree	22.7 percentage of participants	21.1 percentage of participants	15 percentage of participants	—
Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) Question b: Slightly Disagree	0 percentage of participants	0 percentage of participants	0 percentage of participants	—
Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) Question b: Disagree	0 percentage of participants	0 percentage of participants	0 percentage of participants	—
Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) Question c: Agree	4.5 percentage of participants	26.3 percentage of participants	20 percentage of participants	—
Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) Question d: Slightly Disagree	0 percentage of participants	5.3 percentage of participants	15 percentage of participants	—
Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) Question d: Disagree	27.3 percentage of participants	31.6 percentage of participants	40 percentage of participants	—
Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) Question e: Agree	63.6 percentage of participants	84.2 percentage of participants	80 percentage of participants	—
Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) Question e: Slightly Agree	13.6 percentage of participants	0 percentage of participants	5 percentage of participants	—
Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) Question e: Neither Agree Nor Disagree	22.7 percentage of participants	15.8 percentage of participants	15 percentage of participants	—
Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) Question e: Slightly Disagree	0 percentage of participants	0 percentage of participants	0 percentage of participants	—
Alzheimer's Disease Medication Administration Concerns Questionnaire (AD MACQ) Question e: Disagree	0 percentage of participants	0 percentage of participants	0 percentage of participants	—

Adverse Events

ACC 3 μg+QS-21

Serious events: 1 serious events

Other events: 20 other events

Deaths: 0 deaths

ACC 10 μg+QS-21

Serious events: 6 serious events

Other events: 19 other events

Deaths: 0 deaths

Placebo

Serious events: 6 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Measure	ACC 3 μg+QS-21 n=22 participants at risk Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	ACC 10 μg+QS-21 n=20 participants at risk Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Placebo n=21 participants at risk Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphoproliferative disorder	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neurilemmoma benign	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Parathyroid tumour benign	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.8% 1/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pleomorphic adenoma	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.8% 1/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Urinary tract infection	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.8% 1/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Diverticulitis	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Pneumonia	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Asthenia	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.8% 1/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Chest discomfort	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.8% 1/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Chest pain	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.8% 1/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Cardiac disorders Aortic valve incompetence	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.8% 1/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Cardiac disorders Atrial fibrillation	4.5% 1/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Femur fracture	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.8% 1/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Dehydration	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.8% 1/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Autonomic nervous system imbalance	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.8% 1/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Syncope	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.8% 1/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Delirium	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.8% 1/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Vascular disorders Hypotension	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.8% 1/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.

Other adverse events

Measure	ACC 3 μg+QS-21 n=22 participants at risk Participants received 3 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	ACC 10 μg+QS-21 n=20 participants at risk Participants received 10 μg of ACC-001 and 50 μg of QS-21. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.	Placebo n=21 participants at risk Participants received PBS. Investigational product was administered by intramuscular injection into the deltoid muscle at 0, 1, 3, 6, 12, and 18 months.
Surgical and medical procedures Dental implantation	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Cardiac disorders Aortic valve calcification	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Cardiac disorders Sinus bradycardia	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Dehydration	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hypercholesterolaemia	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Ear and labyrinth disorders Ear disorder	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Injection site reaction	68.2% 15/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	80.0% 16/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	23.8% 5/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Fatigue	9.1% 2/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	10.0% 2/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.8% 1/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Asthenia	4.5% 1/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.8% 1/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Injection site haemorrhage	13.6% 3/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Gait disturbance	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	9.5% 2/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Injection site pruritus	4.5% 1/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Irritability	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.8% 1/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Influenza like illness	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Pyrexia	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Upper respiratory tract infection	22.7% 5/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	25.0% 5/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	14.3% 3/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Nasopharyngitis	18.2% 4/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	15.0% 3/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	9.5% 2/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Bronchitis	4.5% 1/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	15.0% 3/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.8% 1/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Sinusitis	13.6% 3/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	10.0% 2/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Urinary tract infection	4.5% 1/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	15.0% 3/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.8% 1/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Influenza	4.5% 1/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	9.5% 2/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Lower respiratory tract infection	4.5% 1/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.8% 1/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Pneumonia	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	10.0% 2/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Diverticulitis	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Gastroenteritis viral	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Herpes zoster	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Infectious mononucleosis	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Oral herpes	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Headache	13.6% 3/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	20.0% 4/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	14.3% 3/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Dizziness	13.6% 3/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	15.0% 3/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	9.5% 2/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Cerebral microhaemorrhage	4.5% 1/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.8% 1/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Dementia Alzheimers type	9.1% 2/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.8% 1/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Cognitive disorder	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.8% 1/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Nerve compression	4.5% 1/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Nervous system disorder	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.8% 1/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Aphasia	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Hypertonia	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Lethargy	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Presyncope	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Diarrhoea	18.2% 4/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	15.0% 3/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.8% 1/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Nausea	13.6% 3/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	15.0% 3/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.8% 1/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Vomiting	9.1% 2/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	10.0% 2/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	9.5% 2/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal pain upper	9.1% 2/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Constipation	9.1% 2/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Dyspepsia	4.5% 1/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal distension	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Dental caries	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Gastroduodenitis	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Toothache	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Arthralgia	4.5% 1/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	20.0% 4/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Pain in extremity	9.1% 2/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	9.5% 2/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	10.0% 2/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.8% 1/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Fibromyalgia	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	10.0% 2/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	9.5% 2/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	4.5% 1/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Exostosis	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Intervertebral disc degeneration	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Joint stiffness	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Spinal column stenosis	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Spondylolisthesis	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Fall	4.5% 1/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	10.0% 2/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	9.5% 2/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Contusion	4.5% 1/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	10.0% 2/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.8% 1/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Procedural pain	9.1% 2/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.8% 1/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Arthropod bite	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	10.0% 2/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.8% 1/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Laceration	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	10.0% 2/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.8% 1/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Post lumbar puncture syndrome	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	15.0% 3/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Excoriation	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Head injury	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Post-traumatic pain	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Anxiety	13.6% 3/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	10.0% 2/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	14.3% 3/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Grief reaction	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Paranoia	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Dermal cyst	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.8% 1/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Ecchymosis	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.8% 1/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Rash	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.8% 1/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Blister	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Erythema	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Rash papular	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Vascular disorders Hypertension	4.5% 1/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Vascular disorders Varicose vein	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.8% 1/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Vascular disorders Aortic stenosis	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Vascular disorders Flushing	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Vascular disorders Hot flush	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Investigations Weight decreased	4.5% 1/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.8% 1/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Investigations Blood pressure increased	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Investigations Intraocular pressure increased	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Investigations Nuclear magnetic resonance imaging brain abnormal	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Cough	9.1% 2/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.8% 1/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Sinus congestion	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Eye disorders Cataract	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.8% 1/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Eye disorders Eye inflammation	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Pollakiuria	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	9.5% 2/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Nephrolithiasis	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Surgical and medical procedures Skin neoplasm excision	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	10.0% 2/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Surgical and medical procedures Colon operation	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lipoma	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Reproductive system and breast disorders Vaginal haemorrhage	0.00% 0/22 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.0% 1/20 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/21 • From Day 1 throughout the study (104 weeks). The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: ClinicalTrials.gov_Inquiries@pfizer.com

Results disclosure agreements

• Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
• Publication restrictions are in place

Restriction type: OTHER