Trial Outcomes & Findings for Safety and Immunogenicity of Repeated Doses of ABvac40 in Patients With a-MCI or Vm-AD (NCT NCT03461276)

NCT ID: NCT03461276

Last Updated: 2025-02-03

Results Overview

Average maximal increment (MΔ) of plasma anti-Aβ40 antibody signal (optical density \[OD\] in ELISA) in each subject with regard to Baseline visit.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 134 participants
• Primary outcome timeframe: Part A (Baseline, and post-Baseline visits at Week 2A, Week 6A, Week 10A, Week 14A, Week 18A, Week 24A, Week 40A, Week 44A, Week 50A, Week 77A, and Week 104A)
• Results posted on: 2025-02-03

Participant Flow

A total of 23 centers in Spain (n=18), France (n=3), Italy (n=1) and Sweden (n=1) recruited subjects in this study. The subjects' recruitment was competitive until the required number of subjects was completed.

238 subjects were screened and assessed for eligibility. 88 subjects were screening failures and an additional 16 subjects dropped out the study before being randomized. 134 subjects were randomized. Finally, 10 randomized subjects did not receive the allocated IMP. Accordingly, 124 subjects received any IMP dose, constituting the SAF analysis set.

Participant milestones

Measure	Placebo Arm Part A/ABvac40 Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with placebo plus a placebo booster shot in Part A (Placebo arm Part A). In Part B, subjects received 5 monthly (every 4 weeks) immunizations with ABvac40 plus an ABvac40 booster shot after 6 months (ABvac40 arm Part B).	ABvac40 Arm Part A/Placebo+Booster Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with ABvac40 plus an ABvac40 booster shot in Part A (ABvac40 arm Part A). In Part B, the subjects received placebo following this schedule, except in V13B, where they received an ABvac40 booster shot (Placebo + Booster arm Part B).
Part A (18-24 Months Duration) STARTED	62	62
Part A (18-24 Months Duration) COMPLETED	53	55
Part A (18-24 Months Duration) NOT COMPLETED	9	7
Part B (18 Months Duration) STARTED	37	40
Part B (18 Months Duration) COMPLETED	33	38
Part B (18 Months Duration) NOT COMPLETED	4	2

Reasons for withdrawal

Measure	Placebo Arm Part A/ABvac40 Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with placebo plus a placebo booster shot in Part A (Placebo arm Part A). In Part B, subjects received 5 monthly (every 4 weeks) immunizations with ABvac40 plus an ABvac40 booster shot after 6 months (ABvac40 arm Part B).	ABvac40 Arm Part A/Placebo+Booster Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with ABvac40 plus an ABvac40 booster shot in Part A (ABvac40 arm Part A). In Part B, the subjects received placebo following this schedule, except in V13B, where they received an ABvac40 booster shot (Placebo + Booster arm Part B).
Part A (18-24 Months Duration) Adverse event, serious fatal	1	1
Part A (18-24 Months Duration) Physician Decision	1	0
Part A (18-24 Months Duration) Withdrawal by Subject	1	1
Part A (18-24 Months Duration) Adverse event, non-fatal	3	1
Part A (18-24 Months Duration) Patient heath status	0	1
Part A (18-24 Months Duration) Patient/caregiver's decision	3	3
Part B (18 Months Duration) Lost to Follow-up	1	0
Part B (18 Months Duration) Withdrawal by Subject	0	1
Part B (18 Months Duration) Adverse event, non-fatal	0	1
Part B (18 Months Duration) Patient/caregiver's decision	3	0

Baseline Characteristics

Safety and Immunogenicity of Repeated Doses of ABvac40 in Patients With a-MCI or Vm-AD

Baseline characteristics by cohort

Measure	Placebo Arm Part A n=62 Participants Subjects who received Placebo during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 vehicle without its active ingredient.	ABvac40 Arm Part A n=62 Participants Subjects who received ABvac40 during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 (containing 0.2 mg of Aβx-40).	Total n=124 Participants Total of all reporting groups
Age, Continuous	70.1 years STANDARD_DEVIATION 5.49 • n=5 Participants	70.6 years STANDARD_DEVIATION 5.95 • n=7 Participants	70.4 years STANDARD_DEVIATION 5.71 • n=5 Participants
Sex: Female, Male Female	36 Participants n=5 Participants	38 Participants n=7 Participants	74 Participants n=5 Participants
Sex: Female, Male Male	26 Participants n=5 Participants	24 Participants n=7 Participants	50 Participants n=5 Participants
Race/Ethnicity, Customized Asian/Pacific islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Black	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	60 Participants n=5 Participants	58 Participants n=7 Participants	118 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Missing	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Study Disease amnestic Mild Cognitive Impairment (a-MCI)	42 Participants n=5 Participants	38 Participants n=7 Participants	80 Participants n=5 Participants
Study Disease Very Mild Alzheimer's Disease (VMAD)	20 Participants n=5 Participants	24 Participants n=7 Participants	44 Participants n=5 Participants
Amyloid-positron Emission Tomography (a-PET) Status Positive	45 Participants n=5 Participants	47 Participants n=7 Participants	92 Participants n=5 Participants
Amyloid-positron Emission Tomography (a-PET) Status Negative	17 Participants n=5 Participants	15 Participants n=7 Participants	32 Participants n=5 Participants
Apolipoprotein E (ApoE) Status Noncarriers: E2/E2 and E2/E3, E3/E3	24 Participants n=5 Participants	24 Participants n=7 Participants	48 Participants n=5 Participants
Apolipoprotein E (ApoE) Status Carriers (Heterozygous: E2/E4, E3/E4)	33 Participants n=5 Participants	29 Participants n=7 Participants	62 Participants n=5 Participants
Apolipoprotein E (ApoE) Status Carriers (Homozygous: E4/E4)	5 Participants n=5 Participants	9 Participants n=7 Participants	14 Participants n=5 Participants
Time from Disease Diagnosis to Informed Consent	14.48 months STANDARD_DEVIATION 15.81 • n=5 Participants	14.68 months STANDARD_DEVIATION 13.71 • n=7 Participants	14.58 months STANDARD_DEVIATION 14.74 • n=5 Participants

PRIMARY outcome

Timeframe: Part A (Baseline, and post-Baseline visits at Week 2A, Week 6A, Week 10A, Week 14A, Week 18A, Week 24A, Week 40A, Week 44A, Week 50A, Week 77A, and Week 104A)

Population: The Modified Intent-to-treat (mITT) analysis set comprised all subjects in the ITT analysis set who had a Baseline- and at least 1 post-Baseline anti-Aβ40 antibody assessment (optical density \[OD\] in ELISA without pre-adsorption). Analysis of the primary efficacy endpoint was carried out using the mITT analysis set. Subjects were analyzed according to their randomized treatment assignment, regardless of the treatment received.

Average maximal increment (MΔ) of plasma anti-Aβ40 antibody signal (optical density [OD] in ELISA) in each subject with regard to Baseline visit.

Outcome measures

Measure	Placebo Arm Part A n=60 Participants Subjects who received Placebo during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 vehicle without its active ingredient.	ABvac40 Arm Part A n=61 Participants Subjects who received ABvac40 during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 (containing 0.2 mg of Aβx-40).	ABvac40 Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with ABvac40 plus an ABvac40 booster shot after 6 months in Part B.	Placebo+Booster Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with placebo plus an ABvac40 booster shot at Visit 13 in Part B.
Average Maximal Increment of Anti-Aβ40 Antibody Signal (Optical Density [OD] in ELISA)	0.12 OD Standard Deviation 0.21	3.27 OD Standard Deviation 0.75	—	—

SECONDARY outcome

Timeframe: Entire study duration (Week 0 to Week 104 in Part A, and Week 0 to Week 77 in Part B)

Population: The safety analysis set consisted of all randomized subjects who received any amount of IMP. All safety analyses used the SAF analysis set. Subjects were analyzed according to the treatment received, regardless of the treatment assigned.

Number of withdrawn subjects due to treatment-emergent adverse events (TEAEs) during the whole study.

Outcome measures

Measure	Placebo Arm Part A n=60 Participants Subjects who received Placebo during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 vehicle without its active ingredient.	ABvac40 Arm Part A n=64 Participants Subjects who received ABvac40 during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 (containing 0.2 mg of Aβx-40).	ABvac40 Arm Part B n=37 Participants Subjects received 5 monthly (every 4 weeks) immunizations with ABvac40 plus an ABvac40 booster shot after 6 months in Part B.	Placebo+Booster Arm Part B n=40 Participants Subjects received 5 monthly (every 4 weeks) immunizations with placebo plus an ABvac40 booster shot at Visit 13 in Part B.
Subject Discontinuations Due to TEAEs	4 Participants	2 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Entire study duration (Week 0 to Week 104 in Part A, and Week 0 to Week 77 in Part B)

Population: The safety analysis set consisted of all randomized subjects who received any amount of IMP. All safety analyses used the SAF analysis set. Subjects were analyzed according to the treatment received, regardless of the treatment assigned.

Clinically significant (CS) abnormalities in physical examination reported during the study.

Outcome measures

Measure	Placebo Arm Part A n=60 Participants Subjects who received Placebo during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 vehicle without its active ingredient.	ABvac40 Arm Part A n=64 Participants Subjects who received ABvac40 during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 (containing 0.2 mg of Aβx-40).	ABvac40 Arm Part B n=37 Participants Subjects received 5 monthly (every 4 weeks) immunizations with ABvac40 plus an ABvac40 booster shot after 6 months in Part B.	Placebo+Booster Arm Part B n=40 Participants Subjects received 5 monthly (every 4 weeks) immunizations with placebo plus an ABvac40 booster shot at Visit 13 in Part B.
Number of Subjects With Clinically Significant Abnormalities in Physical Examination	4 Participants	1 Participants	4 Participants	2 Participants

SECONDARY outcome

Timeframe: Entire study duration (Week 0 to Week 104 in Part A, and Week 0 to Week 77 in Part B)

Population: The safety analysis set consisted of all randomized subjects who received any amount of IMP. All safety analyses used the SAF analysis set. Subjects were analyzed according to the treatment received, regardless of the treatment assigned.

Clinically significant (CS) abnormalities in neurological examination reported during the study.

Outcome measures

Measure	Placebo Arm Part A n=60 Participants Subjects who received Placebo during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 vehicle without its active ingredient.	ABvac40 Arm Part A n=64 Participants Subjects who received ABvac40 during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 (containing 0.2 mg of Aβx-40).	ABvac40 Arm Part B n=37 Participants Subjects received 5 monthly (every 4 weeks) immunizations with ABvac40 plus an ABvac40 booster shot after 6 months in Part B.	Placebo+Booster Arm Part B n=40 Participants Subjects received 5 monthly (every 4 weeks) immunizations with placebo plus an ABvac40 booster shot at Visit 13 in Part B.
Number of Subjects With Clinically Significant Abnormalities in Neurological Examination	6 Participants	5 Participants	2 Participants	1 Participants

SECONDARY outcome

Timeframe: Entire study duration (Week 0 to Week 104 in Part A, and Week 0 to Week 77 in Part B)

Population: The safety analysis set consisted of all randomized subjects who received any amount of IMP. All safety analyses used the SAF analysis set. Subjects were analyzed according to the treatment received, regardless of the treatment assigned.

Clinically significant (CS) abnormalities in hematology parameters reported during the study.

Outcome measures

Measure	Placebo Arm Part A n=60 Participants Subjects who received Placebo during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 vehicle without its active ingredient.	ABvac40 Arm Part A n=64 Participants Subjects who received ABvac40 during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 (containing 0.2 mg of Aβx-40).	ABvac40 Arm Part B n=37 Participants Subjects received 5 monthly (every 4 weeks) immunizations with ABvac40 plus an ABvac40 booster shot after 6 months in Part B.	Placebo+Booster Arm Part B n=40 Participants Subjects received 5 monthly (every 4 weeks) immunizations with placebo plus an ABvac40 booster shot at Visit 13 in Part B.
Number of Subjects With Clinically Significant Abnormalities in Analytical Hematology	5 Participants	4 Participants	0 Participants	6 Participants

SECONDARY outcome

Timeframe: Entire study duration (Week 0 to Week 104 in Part A, and Week 0 to Week 77 in Part B)

Population: The safety analysis set consisted of all randomized subjects who received any amount of IMP. All safety analyses used the SAF analysis set. Subjects were analyzed according to the treatment received, regardless of the treatment assigned.

Clinically significant (CS) abnormalities in biochemistry parameters reported during the study.

Outcome measures

Measure	Placebo Arm Part A n=60 Participants Subjects who received Placebo during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 vehicle without its active ingredient.	ABvac40 Arm Part A n=64 Participants Subjects who received ABvac40 during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 (containing 0.2 mg of Aβx-40).	ABvac40 Arm Part B n=37 Participants Subjects received 5 monthly (every 4 weeks) immunizations with ABvac40 plus an ABvac40 booster shot after 6 months in Part B.	Placebo+Booster Arm Part B n=40 Participants Subjects received 5 monthly (every 4 weeks) immunizations with placebo plus an ABvac40 booster shot at Visit 13 in Part B.
Number of Subjects With Clinically Significant Abnormalities in Analytical Biochemistry	12 Participants	5 Participants	6 Participants	6 Participants

SECONDARY outcome

Timeframe: Entire study duration (Week 0 to Week 104 in Part A, and Week 0 to Week 77 in Part B)

Population: The safety analysis set consisted of all randomized subjects who received any amount of IMP. All safety analyses used the SAF analysis set. Subjects were analyzed according to the treatment received, regardless of the treatment assigned.

Clinically significant (CS) abnormalities in coagulation parameters reported during the study.

Outcome measures

Measure	Placebo Arm Part A n=60 Participants Subjects who received Placebo during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 vehicle without its active ingredient.	ABvac40 Arm Part A n=64 Participants Subjects who received ABvac40 during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 (containing 0.2 mg of Aβx-40).	ABvac40 Arm Part B n=37 Participants Subjects received 5 monthly (every 4 weeks) immunizations with ABvac40 plus an ABvac40 booster shot after 6 months in Part B.	Placebo+Booster Arm Part B n=40 Participants Subjects received 5 monthly (every 4 weeks) immunizations with placebo plus an ABvac40 booster shot at Visit 13 in Part B.
Number of Subjects With Clinically Significant Abnormalities in Coagulation	4 Participants	1 Participants	3 Participants	2 Participants

SECONDARY outcome

Timeframe: Part A (Week 50A and Week 104A)

Population: The Intent-to-treat (ITT) analysis set consisted of all subjects randomized who received any IMP. Analysis of all secondary efficacy endpoints was carried out using the ITT analysis set. Subjects were analyzed according to their randomized treatment. assignment, regardless of the treatment received

The change in levels of anti-Aβ40 antibodies in cerebrospinal fluid (CSF) from baseline to each applicable post-baseline efficacy visit (Part A) was analyzed using a Mixed-Model Repeated Measures (MMRM), and the ITT analysis set.

The MMRM included the recorded outcome value as the dependent variable; treatment, protocol specified visits, treatment-by-visit interaction, and amyloid positivity as the fixed effects; baseline age as covariates; and measures within-patient at each visit as a repeated measure. An unstructured variance-covariance matrix was used. The following factors may also have be included in the model: ApoE carrier status, baseline use of AD symptomatic medication and clinical subgroup - MCI or vmAD, if found to be significantly associated with the response measure (p < 0.15).

Outcome measures

Measure	Placebo Arm Part A n=62 Participants Subjects who received Placebo during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 vehicle without its active ingredient.	ABvac40 Arm Part A n=62 Participants Subjects who received ABvac40 during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 (containing 0.2 mg of Aβx-40).	ABvac40 Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with ABvac40 plus an ABvac40 booster shot after 6 months in Part B.	Placebo+Booster Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with placebo plus an ABvac40 booster shot at Visit 13 in Part B.
Level of Anti-Aβ40 Antibodies in CSF Week 50A	0.1654 ng/mL Standard Error 3.86502	30.1826 ng/mL Standard Error 3.90756	—	—
Level of Anti-Aβ40 Antibodies in CSF Week 104A	0.2014 ng/mL Standard Error 0.36753	1.2437 ng/mL Standard Error 0.41902	—	—

SECONDARY outcome

Timeframe: Part A (Week 2A, Week 6A, Week 10A, Week 14A, Week 18A, Week 24A, Week 40A, Week 44A, Week 50A, Week 77A, and Week 104A)

Population: The Intent-to-treat (ITT) analysis set consisted of all subjects randomized who received any IMP. Analysis of all secondary efficacy endpoints was carried out using the ITT analysis set. Subjects were analyzed according to their randomized treatment assignment, regardless of the treatment received.

The change in levels of anti-Aβ40 antibodies in plasma from baseline to each applicable post-baseline efficacy visit (Part A) was analyzed using a Mixed-Model Repeated Measures (MMRM), and the ITT analysis set.

The MMRM included the recorded outcome value as the dependent variable; treatment, protocol specified visits, treatment-by-visit interaction, and amyloid positivity as the fixed effects; baseline age as covariates; and measures within-patient at each visit as a repeated measure. A compound symmetric variance-covariance matrix was used. The following factors may also have be included in the model: ApoE carrier status, baseline use of AD symptomatic medication and clinical subgroup - MCI or vmAD, if found to be significantly associated with the response measure (p < 0.15).

Outcome measures

Measure	Placebo Arm Part A n=62 Participants Subjects who received Placebo during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 vehicle without its active ingredient.	ABvac40 Arm Part A n=62 Participants Subjects who received ABvac40 during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 (containing 0.2 mg of Aβx-40).	ABvac40 Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with ABvac40 plus an ABvac40 booster shot after 6 months in Part B.	Placebo+Booster Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with placebo plus an ABvac40 booster shot at Visit 13 in Part B.
Level of Anti-Aβ40 Antibodies in Plasma Week 2A	1.5580 μg/mL Standard Error 4.22100	1.5112 μg/mL Standard Error 4.40221	—	—
Level of Anti-Aβ40 Antibodies in Plasma Week 6A	1.5580 μg/mL Standard Error 4.22100	13.7052 μg/mL Standard Error 4.44801	—	—
Level of Anti-Aβ40 Antibodies in Plasma Week 10A	1.6172 μg/mL Standard Error 4.24276	44.3187 μg/mL Standard Error 4.41509	—	—
Level of Anti-Aβ40 Antibodies in Plasma Week 14A	1.5479 μg/mL Standard Error 4.24276	62.1946 μg/mL Standard Error 4.43781	—	—
Level of Anti-Aβ40 Antibodies in Plasma Week 18A	1.5789 μg/mL Standard Error 4.30746	69.8861 μg/mL Standard Error 4.43781	—	—
Level of Anti-Aβ40 Antibodies in Plasma Week 24A	1.5926 μg/mL Standard Error 4.26432	39.9483 μg/mL Standard Error 4.44151	—	—
Level of Anti-Aβ40 Antibodies in Plasma Week 40A	1.6027 μg/mL Standard Error 4.33264	14.6139 μg/mL Standard Error 4.48526	—	—
Level of Anti-Aβ40 Antibodies in Plasma Week 44A	1.5463 μg/mL Standard Error 4.35267	57.5771 μg/mL Standard Error 4.48568	—	—
Level of Anti-Aβ40 Antibodies in Plasma Week 50A	1.5993 μg/mL Standard Error 4.35363	33.5366 μg/mL Standard Error 4.51418	—	—
Level of Anti-Aβ40 Antibodies in Plasma Week 77A	1.5232 μg/mL Standard Error 4.37735	10.8197 μg/mL Standard Error 4.57100	—	—
Level of Anti-Aβ40 Antibodies in Plasma Week 104A	1.7400 μg/mL Standard Error 5.57743	10.8365 μg/mL Standard Error 5.82224	—	—

SECONDARY outcome

Timeframe: Part A (Week 2A, Week 6A, Week 10A, Week 14A, Week 18A, Week 24A, Week 40A, Week 44A, Week 50A, Week 77A, and Week 104A)

Population: The Intent-to-treat (ITT) analysis set consisted of all subjects randomized who received any IMP. Analysis of all secondary efficacy endpoints was carried out using the ITT analysis set. Subjects were analyzed according to their randomized treatment assignment, regardless of the treatment received.

The change in levels of antibody-secreting cells from baseline to each applicable post-baseline efficacy visit (Part A) was analyzed using a Mixed-Model Repeated Measures (MMRM), and the ITT analysis set.

The MMRM included the recorded outcome value as the dependent variable; treatment, protocol-specified visits, treatment-by-visit interaction, and amyloid positivity as the fixed effects; baseline age as covariates; and measures within-patient at each visit as a repeated measure. An unstructured variance-covariance matrix was used. The following factors may also have be included in the model: ApoE carrier status, baseline use of AD symptomatic medication and clinical subgroup - MCI or vmAD, if found to be significantly associated with the response measure (p < 0.15).

Outcome measures

Measure	Placebo Arm Part A n=62 Participants Subjects who received Placebo during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 vehicle without its active ingredient.	ABvac40 Arm Part A n=62 Participants Subjects who received ABvac40 during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 (containing 0.2 mg of Aβx-40).	ABvac40 Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with ABvac40 plus an ABvac40 booster shot after 6 months in Part B.	Placebo+Booster Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with placebo plus an ABvac40 booster shot at Visit 13 in Part B.
Level of Antibody-secreting Cells Week 2A	-0.4365 SFU/0.5x10^6 PBMCs Standard Error 0.37501	0.1868 SFU/0.5x10^6 PBMCs Standard Error 0.34352	—	—
Level of Antibody-secreting Cells Week 6A	-0.0906 SFU/0.5x10^6 PBMCs Standard Error 0.72718	2.3144 SFU/0.5x10^6 PBMCs Standard Error 0.67867	—	—
Level of Antibody-secreting Cells Week 10A	0.3092 SFU/0.5x10^6 PBMCs Standard Error 0.79081	4.0397 SFU/0.5x10^6 PBMCs Standard Error 0.73611	—	—
Level of Antibody-secreting Cells Week 14A	-0.1484 SFU/0.5x10^6 PBMCs Standard Error 1.44968	7.5119 SFU/0.5x10^6 PBMCs Standard Error 1.36804	—	—
Level of Antibody-secreting Cells Week 18A	0.2873 SFU/0.5x10^6 PBMCs Standard Error 1.02944	6.8827 SFU/0.5x10^6 PBMCs Standard Error 0.93624	—	—
Level of Antibody-secreting Cells Week 24A	0.4827 SFU/0.5x10^6 PBMCs Standard Error 0.74628	3.6323 SFU/0.5x10^6 PBMCs Standard Error 0.68609	—	—
Level of Antibody-secreting Cells Week 40A	-0.5201 SFU/0.5x10^6 PBMCs Standard Error 0.41447	1.2117 SFU/0.5x10^6 PBMCs Standard Error 0.37194	—	—
Level of Antibody-secreting Cells Week 44A	-1.1915 SFU/0.5x10^6 PBMCs Standard Error 2.45820	10.3597 SFU/0.5x10^6 PBMCs Standard Error 2.23485	—	—
Level of Antibody-secreting Cells Week 50A	-0.3489 SFU/0.5x10^6 PBMCs Standard Error 1.07737	4.5496 SFU/0.5x10^6 PBMCs Standard Error 1.00962	—	—
Level of Antibody-secreting Cells Week 77A	-0.3969 SFU/0.5x10^6 PBMCs Standard Error 0.52153	1.8382 SFU/0.5x10^6 PBMCs Standard Error 0.47244	—	—
Level of Antibody-secreting Cells Week 104A	0.1732 SFU/0.5x10^6 PBMCs Standard Error 0.40914	0.3638 SFU/0.5x10^6 PBMCs Standard Error 0.40349	—	—

SECONDARY outcome

Timeframe: Part A (Week 2A, Week 6A, Week 10A, Week 14A, Week 18A, Week 24A, Week 40A, Week 44A, Week 50A, Week 77A, and Week 104A)

Population: The Intent-to-treat (ITT) analysis set consisted of all subjects randomized who received any IMP. Analysis of all secondary efficacy endpoints was carried out using the ITT analysis set. Subjects were analyzed according to their randomized treatment assignment, regardless of the treatment received.

The change in levels of anti-Aβ40 peptides in plasma (ABtest-IA) from baseline to each applicable postbaseline efficacy visit (Part A) was analyzed using a Mixed-Model Repeated Measures (MMRM), and the ITT analysis set.

The MMRM included change from baseline in the efficacy parameter as the dependent variable; treatment, protocol-specified visits, treatment-by-visit interaction, and amyloid positivity as the fixed effects; baseline efficacy parameter and baseline age as covariates; and measures within-patient at each visit as a repeated measure. An unstructured variance-covariance matrix was used. The following factors may also have be included in the model: ApoE carrier status, baseline use of AD symptomatic medication and clinical subgroup - MCI or vmAD, if found to be significantly associated with the response measure (p < 0.15).

Outcome measures

Measure	Placebo Arm Part A n=62 Participants Subjects who received Placebo during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 vehicle without its active ingredient.	ABvac40 Arm Part A n=62 Participants Subjects who received ABvac40 during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 (containing 0.2 mg of Aβx-40).	ABvac40 Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with ABvac40 plus an ABvac40 booster shot after 6 months in Part B.	Placebo+Booster Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with placebo plus an ABvac40 booster shot at Visit 13 in Part B.
Level of Aβ40 Peptides in Plasma - ABtest-IA Week 2A	2.5948 pg/mL Standard Error 2.22120	3.4620 pg/mL Standard Error 2.16724	—	—
Level of Aβ40 Peptides in Plasma - ABtest-IA Week 6A	3.2541 pg/mL Standard Error 2.66184	8.3468 pg/mL Standard Error 2.60510	—	—
Level of Aβ40 Peptides in Plasma - ABtest-IA Week 10A	4.2669 pg/mL Standard Error 3.43764	-3.3200 pg/mL Standard Error 3.38626	—	—
Level of Aβ40 Peptides in Plasma - ABtest-IA Week 14A	4.7946 pg/mL Standard Error 4.75127	-10.5837 pg/mL Standard Error 4.71154	—	—
Level of Aβ40 Peptides in Plasma - ABtest-IA Week 18A	7.7216 pg/mL Standard Error 4.68637	-13.4213 pg/mL Standard Error 4.61987	—	—
Level of Aβ40 Peptides in Plasma - ABtest-IA Week 24A	6.3608 pg/mL Standard Error 4.06529	-30.6595 pg/mL Standard Error 4.00199	—	—
Level of Aβ40 Peptides in Plasma - ABtest-IA Week 40A	4.7336 pg/mL Standard Error 4.73069	-43.2898 pg/mL Standard Error 4.62000	—	—
Level of Aβ40 Peptides in Plasma - ABtest-IA Week 44A	7.4722 pg/mL Standard Error 5.45150	-36.7343 pg/mL Standard Error 5.32882	—	—
Level of Aβ40 Peptides in Plasma - ABtest-IA Week 50A	6.5136 pg/mL Standard Error 5.56714	-36.9475 pg/mL Standard Error 5.43416	—	—
Level of Aβ40 Peptides in Plasma - ABtest-IA Week 77A	9.9852 pg/mL Standard Error 5.15517	-31.8000 pg/mL Standard Error 5.04184	—	—
Level of Aβ40 Peptides in Plasma - ABtest-IA Week 104A	7.9352 pg/mL Standard Error 7.65221	-16.5218 pg/mL Standard Error 7.67117	—	—

SECONDARY outcome

Timeframe: Part A (Week 2A, Week 6A, Week 10A, Week 14A, Week 18A, Week 24A, Week 40A, Week 44A, Week 50A, Week 77A, and Week 104A)

Population: The Intent-to-treat (ITT) analysis set consisted of all subjects randomized who received any IMP. Analysis of all secondary efficacy endpoints was carried out using the ITT analysis set. Subjects were analyzed according to their randomized treatment assignment, regardless of the treatment received.

The change in levels of anti-Aβ42 peptides in plasma (ABtest-IA) from baseline to each applicable postbaseline efficacy visit (Part A) was analyzed using a Mixed-Model Repeated Measures (MMRM), and the ITT analysis set.

The MMRM included change from baseline in the efficacy parameter as the dependent variable; treatment, protocol-specified visits, treatment-by-visit interaction, and amyloid positivity as the fixed effects; baseline efficacy parameter and baseline age as covariates; and measures within-patient at each visit as a repeated measure. An unstructured variance-covariance matrix was used. The following factors may also have be included in the model: ApoE carrier status, baseline use of AD symptomatic medication and clinical subgroup - MCI or vmAD, if found to be significantly associated with the response measure (p < 0.15).

Outcome measures

Measure	Placebo Arm Part A n=62 Participants Subjects who received Placebo during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 vehicle without its active ingredient.	ABvac40 Arm Part A n=62 Participants Subjects who received ABvac40 during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 (containing 0.2 mg of Aβx-40).	ABvac40 Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with ABvac40 plus an ABvac40 booster shot after 6 months in Part B.	Placebo+Booster Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with placebo plus an ABvac40 booster shot at Visit 13 in Part B.
Level of Aβ42 Peptides in Plasma - ABtest-IA Week 2A	0.6745 pg/mL Standard Error 0.47690	0.3868 pg/mL Standard Error 0.47126	—	—
Level of Aβ42 Peptides in Plasma - ABtest-IA Week 6A	1.2776 pg/mL Standard Error 0.77358	1.6248 pg/mL Standard Error 0.76131	—	—
Level of Aβ42 Peptides in Plasma - ABtest-IA Week 10A	1.2091 pg/mL Standard Error 0.88576	2.1331 pg/mL Standard Error 0.87167	—	—
Level of Aβ42 Peptides in Plasma - ABtest-IA Week 14A	1.6433 pg/mL Standard Error 0.73975	1.0209 pg/mL Standard Error 0.72987	—	—
Level of Aβ42 Peptides in Plasma - ABtest-IA Week 18A	1.9821 pg/mL Standard Error 0.55465	1.2815 pg/mL Standard Error 0.54507	—	—
Level of Aβ42 Peptides in Plasma - ABtest-IA Week 24A	2.8599 pg/mL Standard Error 0.72452	1.6125 pg/mL Standard Error 0.71101	—	—
Level of Aβ42 Peptides in Plasma - ABtest-IA Week 40A	2.0361 pg/mL Standard Error 0.84268	-1.2781 pg/mL Standard Error 0.81992	—	—
Level of Aβ42 Peptides in Plasma - ABtest-IA Week 44A	1.7850 pg/mL Standard Error 1.00896	-0.9785 pg/mL Standard Error 0.98520	—	—
Level of Aβ42 Peptides in Plasma - ABtest-IA Week 50A	2.6958 pg/mL Standard Error 1.24460	0.5563 pg/mL Standard Error 1.21767	—	—
Level of Aβ42 Peptides in Plasma - ABtest-IA Week 77A	2.9304 pg/mL Standard Error 1.15392	0.9045 pg/mL Standard Error 1.13274	—	—
Level of Aβ42 Peptides in Plasma - ABtest-IA Week 104A	0.8402 pg/mL Standard Error 1.36427	0.5027 pg/mL Standard Error 1.34946	—	—

SECONDARY outcome

Timeframe: Part A (Week 2A, Week 6A, Week 10A, Week 14A, Week 18A, Week 24A, Week 40A, Week 44A, Week 50A, Week 77A, and Week 104A)

Population: The Intent-to-treat (ITT) analysis set consisted of all subjects randomized who received any IMP. Analysis of all secondary efficacy endpoints was carried out using the ITT analysis set. Subjects were analyzed according to their randomized treatment assignment, regardless of the treatment received.

The change in levels of anti-Aβ40 peptides in plasma (ABtest-MS) from baseline to each applicable postbaseline efficacy visit (Part A) was analyzed using a Mixed-Model Repeated Measures (MMRM), and the ITT analysis set.

The MMRM included change from baseline in the efficacy parameter as the dependent variable; treatment, protocol-specified visits, treatment-by-visit interaction, and amyloid positivity as the fixed effects; baseline efficacy parameter and baseline age as covariates; and measures within-patient at each visit as a repeated measure. A compound symmetric variance-covariance matrix was used. The following factors may also have be included in the model: ApoE carrier status, baseline use of AD symptomatic medication and clinical subgroup - MCI or vmAD, if found to be significantly associated with the response measure (p < 0.15).

Outcome measures

Measure	Placebo Arm Part A n=62 Participants Subjects who received Placebo during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 vehicle without its active ingredient.	ABvac40 Arm Part A n=62 Participants Subjects who received ABvac40 during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 (containing 0.2 mg of Aβx-40).	ABvac40 Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with ABvac40 plus an ABvac40 booster shot after 6 months in Part B.	Placebo+Booster Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with placebo plus an ABvac40 booster shot at Visit 13 in Part B.
Level of Aβ40 Peptides in Plasma - ABtest-MS Week 40A	-26.9761 pg/mL Standard Error 88.54373	377.7762 pg/mL Standard Error 88.44661	—	—
Level of Aβ40 Peptides in Plasma - ABtest-MS Week 2A	15.0554 pg/mL Standard Error 86.19364	7.2235 pg/mL Standard Error 87.23687	—	—
Level of Aβ40 Peptides in Plasma - ABtest-MS Week 6A	12.9981 pg/mL Standard Error 86.19364	26.8351 pg/mL Standard Error 87.24290	—	—
Level of Aβ40 Peptides in Plasma - ABtest-MS Week 10A	10.8314 pg/mL Standard Error 86.57079	123.0016 pg/mL Standard Error 87.42725	—	—
Level of Aβ40 Peptides in Plasma - ABtest-MS Week 14A	10.1449 pg/mL Standard Error 86.57079	277.9974 pg/mL Standard Error 87.75818	—	—
Level of Aβ40 Peptides in Plasma - ABtest-MS Week 18A	10.1987 pg/mL Standard Error 87.66045	397.6406 pg/mL Standard Error 88.10607	—	—
Level of Aβ40 Peptides in Plasma - ABtest-MS Week 24A	31.0861 pg/mL Standard Error 86.93514	453.1893 pg/mL Standard Error 88.16061	—	—
Level of Aβ40 Peptides in Plasma - ABtest-MS Week 44A	-28.4349 pg/mL Standard Error 88.50690	846.1633 pg/mL Standard Error 88.82717	—	—
Level of Aβ40 Peptides in Plasma - ABtest-MS Week 50A	-34.2153 pg/mL Standard Error 88.91637	628.9483 pg/mL Standard Error 88.88059	—	—
Level of Aβ40 Peptides in Plasma - ABtest-MS Week 77A	-30.9656 pg/mL Standard Error 89.32946	155.5480 pg/mL Standard Error 89.69327	—	—
Level of Aβ40 Peptides in Plasma - ABtest-MS Week 104A	-37.3585 pg/mL Standard Error 110.48329	85.9804 pg/mL Standard Error 113.05734	—	—

SECONDARY outcome

Timeframe: Part A (Week 2A, Week 6A, Week 10A, Week 14A, Week 18A, Week 24A, Week 40A, Week 44A, Week 50A, Week 77A, and Week 104A)

Population: The Intent-to-treat (ITT) analysis set consisted of all subjects randomized who received any IMP. Analysis of all secondary efficacy endpoints was carried out using the ITT analysis set. Subjects were analyzed according to their randomized treatment assignment, regardless of the treatment received.

The change in levels of anti-Aβ42 peptides in plasma (ABtest-MS) from baseline to each applicable postbaseline efficacy visit (Part A) was analyzed using a Mixed-Model Repeated Measures (MMRM), and the ITT analysis set.

The MMRM included change from baseline in the efficacy parameter as the dependent variable; treatment, protocol-specified visits, treatment-by-visit interaction, and amyloid positivity as the fixed effects; baseline efficacy parameter and baseline age as covariates; and measures within-patient at each visit as a repeated measure. An unstructured variance-covariance matrix was used. The following factors may also have be included in the model: ApoE carrier status, baseline use of AD symptomatic medication and clinical subgroup - MCI or vmAD, if found to be significantly associated with the response measure (p < 0.15).

Outcome measures

Measure	Placebo Arm Part A n=62 Participants Subjects who received Placebo during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 vehicle without its active ingredient.	ABvac40 Arm Part A n=62 Participants Subjects who received ABvac40 during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 (containing 0.2 mg of Aβx-40).	ABvac40 Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with ABvac40 plus an ABvac40 booster shot after 6 months in Part B.	Placebo+Booster Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with placebo plus an ABvac40 booster shot at Visit 13 in Part B.
Level of Aβ42 Peptides in Plasma - ABtest-MS Week 2A	-0.1364 pg/mL Standard Error 1.23360	0.0301 pg/mL Standard Error 1.23242	—	—
Level of Aβ42 Peptides in Plasma - ABtest-MS Week 6A	-0.1492 pg/mL Standard Error 1.32406	1.8092 pg/mL Standard Error 1.32222	—	—
Level of Aβ42 Peptides in Plasma - ABtest-MS Week 10A	-1.0248 pg/mL Standard Error 1.33166	0.8740 pg/mL Standard Error 1.32527	—	—
Level of Aβ42 Peptides in Plasma - ABtest-MS Week 14A	0.1680 pg/mL Standard Error 1.15553	0.4841 pg/mL Standard Error 1.15690	—	—
Level of Aβ42 Peptides in Plasma - ABtest-MS Week 18A	0.6469 pg/mL Standard Error 1.51683	-0.9551 pg/mL Standard Error 1.49962	—	—
Level of Aβ42 Peptides in Plasma - ABtest-MS Week 24A	-0.0526 pg/mL Standard Error 1.38574	-1.6059 pg/mL Standard Error 1.38522	—	—
Level of Aβ42 Peptides in Plasma - ABtest-MS Week 40A	2.9633 pg/mL Standard Error 1.71207	3.3472 pg/mL Standard Error 1.68092	—	—
Level of Aβ42 Peptides in Plasma - ABtest-MS Week 44A	1.6060 pg/mL Standard Error 1.52120	1.9498 pg/mL Standard Error 1.49737	—	—
Level of Aβ42 Peptides in Plasma - ABtest-MS Week 50A	0.2069 pg/mL Standard Error 1.49045	2.7196 pg/mL Standard Error 1.46044	—	—
Level of Aβ42 Peptides in Plasma - ABtest-MS Week 77A	1.4766 pg/mL Standard Error 1.61328	4.7243 pg/mL Standard Error 1.58567	—	—
Level of Aβ42 Peptides in Plasma - ABtest-MS Week 104A	4.7604 pg/mL Standard Error 2.18825	2.6870 pg/mL Standard Error 2.19551	—	—

SECONDARY outcome

Timeframe: Part A (Week 50A and Week 104A)

Population: The Intent-to-treat (ITT) analysis set consisted of all subjects randomized who received any IMP. Analysis of all secondary efficacy endpoints was carried out using the ITT analysis set. Subjects were analyzed according to their randomized treatment assignment, regardless of the treatment received.

The change in amyloid-PET (a-PET) standard centiloid global cortical area (reference Pons) from baseline to each applicable post-baseline efficacy visit (Part A) was analyzed using a Mixed-Model Repeated Measures (MMRM), and the ITT analysis set.

The MMRM included change from baseline in the efficacy parameter as the dependent variable; treatment, protocol-specified visits, treatment-by-visit interaction, and amyloid positivity as the fixed effects; baseline efficacy parameter and baseline age as covariates; and measures within-patient at each visit as a repeated measure. An unstructured variance-covariance matrix was used. The following factors may also have be included in the model: ApoE carrier status, baseline use of AD symptomatic medication and clinical subgroup - MCI or vmAD, if found to be significantly associated with the response measure (p < 0.15).

Outcome measures

Measure	Placebo Arm Part A n=62 Participants Subjects who received Placebo during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 vehicle without its active ingredient.	ABvac40 Arm Part A n=62 Participants Subjects who received ABvac40 during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 (containing 0.2 mg of Aβx-40).	ABvac40 Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with ABvac40 plus an ABvac40 booster shot after 6 months in Part B.	Placebo+Booster Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with placebo plus an ABvac40 booster shot at Visit 13 in Part B.
Cortical Fibrillary Amyloid Deposition Assessed by a-PET Scans Week 50A	1.411 Centiloids Standard Error 1.1203	3.561 Centiloids Standard Error 1.0918	—	—
Cortical Fibrillary Amyloid Deposition Assessed by a-PET Scans Week 104A	4.461 Centiloids Standard Error 1.3841	1.241 Centiloids Standard Error 1.5403	—	—

SECONDARY outcome

Timeframe: Part A (Week 24A, Week 50A, and Week 104A)

Population: The Intent-to-treat (ITT) analysis set consisted of all subjects randomized who received any IMP. Analysis of all secondary efficacy endpoints was carried out using the ITT analysis set. Subjects were analyzed according to their randomized treatment assignment, regardless of the treatment received.

The percent change in brain volume from baseline to each applicable post-baseline efficacy visit (Part A) was analyzed using a Mixed-Model Repeated Measures (MMRM), and the ITT analysis set.

The MMRM included change from baseline in the efficacy parameter as the dependent variable; treatment, protocol-specified visits, treatment-by-visit interaction, and amyloid positivity as the fixed effects; baseline efficacy parameter and baseline age as covariates; and measures within-patient at each visit as a repeated measure. An unstructured variance-covariance matrix was used. The following factors may also have be included in the model: ApoE carrier status, baseline use of AD symptomatic medication and clinical subgroup - MCI or vmAD, if found to be significantly associated with the response measure (p < 0.15).

Outcome measures

Measure	Placebo Arm Part A n=62 Participants Subjects who received Placebo during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 vehicle without its active ingredient.	ABvac40 Arm Part A n=62 Participants Subjects who received ABvac40 during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 (containing 0.2 mg of Aβx-40).	ABvac40 Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with ABvac40 plus an ABvac40 booster shot after 6 months in Part B.	Placebo+Booster Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with placebo plus an ABvac40 booster shot at Visit 13 in Part B.
Percentage of Change in Brain Volume Week 24A	-1.39 percent change Standard Error 0.157	-1.40 percent change Standard Error 0.165	—	—
Percentage of Change in Brain Volume Week 50A	-2.05 percent change Standard Error 0.175	-1.75 percent change Standard Error 0.187	—	—
Percentage of Change in Brain Volume Week 104A	-4.16 percent change Standard Error 0.470	-3.11 percent change Standard Error 0.412	—	—

SECONDARY outcome

Timeframe: Part A (Week 24A, Week 50A, Week 104A)

Population: The Intent-to-treat (ITT) analysis set consisted of all subjects randomized who received any IMP. Analysis of all secondary efficacy endpoints was carried out using the ITT analysis set. Subjects were analyzed according to their randomized treatment assignment, regardless of the treatment received.

The percent change in right and left hippocampal volume from baseline to each applicable post-baseline efficacy visit (Part A) was analyzed using a Mixed-Model Repeated Measures (MMRM), and the ITT analysis set.

The MMRM included change from baseline in the efficacy parameter as the dependent variable; treatment, protocol-specified visits, treatment-by-visit interaction, and amyloid positivity as the fixed effects; baseline efficacy parameter and baseline age as covariates; and measures within-patient at each visit as a repeated measure. An unstructured variance-covariance matrix was used. The following factors may also have be included in the model: ApoE carrier status, baseline use of AD symptomatic medication and clinical subgroup - MCI or vmAD, if found to be significantly associated with the response measure (p < 0.15).

Outcome measures

Measure	Placebo Arm Part A n=62 Participants Subjects who received Placebo during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 vehicle without its active ingredient.	ABvac40 Arm Part A n=62 Participants Subjects who received ABvac40 during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 (containing 0.2 mg of Aβx-40).	ABvac40 Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with ABvac40 plus an ABvac40 booster shot after 6 months in Part B.	Placebo+Booster Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with placebo plus an ABvac40 booster shot at Visit 13 in Part B.
Percentage of Change in Hippocampal Volume Week 24A - left	-1.60 percent change Standard Error 0.454	-2.14 percent change Standard Error 0.450	—	—
Percentage of Change in Hippocampal Volume Week 50A - left	-4.13 percent change Standard Error 0.588	-4.24 percent change Standard Error 0.571	—	—
Percentage of Change in Hippocampal Volume Week 104A - left	-7.13 percent change Standard Error 1.060	-8.15 percent change Standard Error 0.965	—	—
Percentage of Change in Hippocampal Volume Week 24A - right	-1.37 percent change Standard Error 0.442	-1.44 percent change Standard Error 0.439	—	—
Percentage of Change in Hippocampal Volume Week 50A - right	-3.34 percent change Standard Error 0.513	-3.23 percent change Standard Error 0.506	—	—
Percentage of Change in Hippocampal Volume Week 104A - right	-6.37 percent change Standard Error 1.001	-6.49 percent change Standard Error 0.901	—	—

SECONDARY outcome

Timeframe: Part A (Week 24A, Week 50A, and Week 104A)

Population: The Intent-to-treat (ITT) analysis set consisted of all subjects randomized who received any IMP. Analysis of all secondary efficacy endpoints was carried out using the ITT analysis set. Subjects were analyzed according to their randomized treatment assignment, regardless of the treatment received.

The percent change in ventricular volume from baseline to each applicable post-baseline efficacy visit (Part A) was analyzed using a Mixed-Model Repeated Measures (MMRM), and the ITT analysis set.

The MMRM included change from baseline in the efficacy parameter as the dependent variable; treatment, protocol-specified visits, treatment-by-visit interaction, and amyloid positivity as the fixed effects; baseline efficacy parameter and baseline age as covariates; and measures within-patient at each visit as a repeated measure. An unstructured variance-covariance matrix was used. The following factors may also have be included in the model: ApoE carrier status, baseline use of AD symptomatic medication and clinical subgroup - MCI or vmAD, if found to be significantly associated with the response measure (p < 0.15).

Outcome measures

Measure	Placebo Arm Part A n=62 Participants Subjects who received Placebo during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 vehicle without its active ingredient.	ABvac40 Arm Part A n=62 Participants Subjects who received ABvac40 during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 (containing 0.2 mg of Aβx-40).	ABvac40 Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with ABvac40 plus an ABvac40 booster shot after 6 months in Part B.	Placebo+Booster Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with placebo plus an ABvac40 booster shot at Visit 13 in Part B.
Percentage of Change in Ventricular Volume Week 24A	5.30 percent change Standard Error 0.584	5.94 percent change Standard Error 0.573	—	—
Percentage of Change in Ventricular Volume Week 50A	10.63 percent change Standard Error 0.809	10.21 percent change Standard Error 0.819	—	—
Percentage of Change in Ventricular Volume Week 104A	22.51 percent change Standard Error 1.887	21.26 percent change Standard Error 1.848	—	—

SECONDARY outcome

Timeframe: Part A (Week 50A and Week 104A)

Population: The Intent-to-treat (ITT) analysis set consisted of all subjects randomized who received any IMP. Analysis of all secondary efficacy endpoints was carried out using the ITT analysis set. Subjects were analyzed according to their randomized treatment assignment, regardless of the treatment received.

The change in levels of Aβ42 peptides in cerebrospinal fluid (CSF) from baseline to each applicable postbaseline efficacy visit (Part A) was analyzed using a Mixed-Model Repeated Measures (MMRM), and the ITT analysis set.

The MMRM included change from baseline in the efficacy parameter as the dependent variable; treatment, protocol-specified visits, treatment-by-visit interaction, and amyloid positivity as the fixed effects; baseline efficacy parameter and baseline age as covariates; and measures within-patient at each visit as a repeated measure. An unstructured variance-covariance matrix was used. The following factors may also have be included in the model: ApoE carrier status, baseline use of AD symptomatic medication and clinical subgroup - MCI or vmAD, if found to be significantly associated with the response measure (p < 0.15).

Outcome measures

Measure	Placebo Arm Part A n=62 Participants Subjects who received Placebo during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 vehicle without its active ingredient.	ABvac40 Arm Part A n=62 Participants Subjects who received ABvac40 during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 (containing 0.2 mg of Aβx-40).	ABvac40 Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with ABvac40 plus an ABvac40 booster shot after 6 months in Part B.	Placebo+Booster Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with placebo plus an ABvac40 booster shot at Visit 13 in Part B.
Level of Aβ42 Peptides in CSF Week 50A	29.0 pg/mL Standard Error 19.40	-2.0 pg/mL Standard Error 19.79	—	—
Level of Aβ42 Peptides in CSF Week 104A	-15.3 pg/mL Standard Error 22.51	4.0 pg/mL Standard Error 25.82	—	—

SECONDARY outcome

Timeframe: Part A (Week 50A and Week 104A)

Population: The Intent-to-treat (ITT) analysis set consisted of all subjects randomized who received any IMP. Analysis of all secondary efficacy endpoints was carried out using the ITT analysis set. Subjects were analyzed according to their randomized treatment assignment, regardless of the treatment received.

The change in levels of Aβ40 peptides in cerebrospinal fluid (CSF) from baseline to each applicable postbaseline efficacy visit (Part A) was analyzed using a Mixed-Model Repeated Measures (MMRM), and the ITT analysis set.

The MMRM included change from baseline in the efficacy parameter as the dependent variable; treatment, protocol-specified visits, treatment-by-visit interaction, and amyloid positivity as the fixed effects; baseline efficacy parameter and baseline age as covariates; and measures within-patient at each visit as a repeated measure. An unstructured variance-covariance matrix was used. The following factors may also have be included in the model: ApoE carrier status, baseline use of AD symptomatic medication and clinical subgroup - MCI or vmAD, if found to be significantly associated with the response measure (p < 0.15).

Outcome measures

Measure	Placebo Arm Part A n=62 Participants Subjects who received Placebo during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 vehicle without its active ingredient.	ABvac40 Arm Part A n=62 Participants Subjects who received ABvac40 during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 (containing 0.2 mg of Aβx-40).	ABvac40 Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with ABvac40 plus an ABvac40 booster shot after 6 months in Part B.	Placebo+Booster Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with placebo plus an ABvac40 booster shot at Visit 13 in Part B.
Level of Aβ40 Peptides in CSF Week 50A	-62.3 pg/mL Standard Error 173.57	-141.8 pg/mL Standard Error 180.07	—	—
Level of Aβ40 Peptides in CSF Week 104A	-652.4 pg/mL Standard Error 227.08	-192.5 pg/mL Standard Error 260.67	—	—

SECONDARY outcome

Timeframe: Part A (Week 50A and Week 104A)

Population: The Intent-to-treat (ITT) analysis set consisted of all subjects randomized who received any IMP. Analysis of all secondary efficacy endpoints was carried out using the ITT analysis set. Subjects were analyzed according to their randomized treatment assignment, regardless of the treatment received.

The change in Aβ42/Aβ40 ratio in cerebrospinal fluid (CSF) from baseline to each applicable postbaseline efficacy visit (Part A) was analyzed using a Mixed-Model Repeated Measures (MMRM), and the ITT analysis set.

The MMRM included change from baseline in the efficacy parameter as the dependent variable; treatment, protocol-specified visits, treatment-by-visit interaction, and amyloid positivity as the fixed effects; baseline efficacy parameter and baseline age as covariates; and measures within-patient at each visit as a repeated measure. An unstructured variance-covariance matrix was used. The following factors may also have be included in the model: ApoE carrier status, baseline use of AD symptomatic medication and clinical subgroup - MCI or vmAD, if found to be significantly associated with the response measure (p < 0.15).

Outcome measures

Measure	Placebo Arm Part A n=62 Participants Subjects who received Placebo during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 vehicle without its active ingredient.	ABvac40 Arm Part A n=62 Participants Subjects who received ABvac40 during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 (containing 0.2 mg of Aβx-40).	ABvac40 Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with ABvac40 plus an ABvac40 booster shot after 6 months in Part B.	Placebo+Booster Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with placebo plus an ABvac40 booster shot at Visit 13 in Part B.
Aβ42/Aβ40 Ratio in CSF Week 50A	0.0005 Ratio Standard Error 0.00135	0.0009 Ratio Standard Error 0.00129	—	—
Aβ42/Aβ40 Ratio in CSF Week 104A	0.0016 Ratio Standard Error 0.00183	0.0020 Ratio Standard Error 0.00205	—	—

SECONDARY outcome

Timeframe: Part A (Week 50A and Week 104A)

Population: The Intent-to-treat (ITT) analysis set consisted of all subjects randomized who received any IMP. Analysis of all secondary efficacy endpoints was carried out using the ITT analysis set. Subjects were analyzed according to their randomized treatment assignment, regardless of the treatment received.

The change in levels of total Tau in cerebrospinal fluid (CSF) from baseline to each applicable postbaseline efficacy visit (Part A) was analyzed using a Mixed-Model Repeated Measures (MMRM), and the ITT analysis set.

The MMRM included change from baseline in the efficacy parameter as the dependent variable; treatment, protocol-specified visits, treatment-by-visit interaction, and amyloid positivity as the fixed effects; baseline efficacy parameter and baseline age as covariates; and measures within-patient at each visit as a repeated measure. An unstructured variance-covariance matrix was used. The following factors may also have be included in the model: ApoE carrier status, baseline use of AD symptomatic medication and clinical subgroup - MCI or vmAD, if found to be significantly associated with the response measure (p < 0.15).

Outcome measures

Measure	Placebo Arm Part A n=62 Participants Subjects who received Placebo during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 vehicle without its active ingredient.	ABvac40 Arm Part A n=62 Participants Subjects who received ABvac40 during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 (containing 0.2 mg of Aβx-40).	ABvac40 Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with ABvac40 plus an ABvac40 booster shot after 6 months in Part B.	Placebo+Booster Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with placebo plus an ABvac40 booster shot at Visit 13 in Part B.
Level of Total Tau in CSF Week 50A	23.4 pg/mL Standard Error 12.20	27.6 pg/mL Standard Error 12.39	—	—
Level of Total Tau in CSF Week 104A	25.9 pg/mL Standard Error 14.20	14.7 pg/mL Standard Error 16.38	—	—

SECONDARY outcome

Timeframe: Part A (Week 50A and Week 104A)

Population: The Intent-to-treat (ITT) analysis set consisted of all subjects randomized who received any IMP. Analysis of all secondary efficacy endpoints was carried out using the ITT analysis set. Subjects were analyzed according to their randomized treatment assignment, regardless of the treatment received.

The change in levels of p-Tau 181 in cerebrospinal fluid (CSF) from baseline to each applicable post-baseline efficacy visit (Part A) was analyzed using a Mixed-Model Repeated Measures (MMRM), and the ITT analysis set.

The MMRM included change from baseline in the efficacy parameter as the dependent variable; treatment, protocol-specified visits, treatment-by-visit interaction, and amyloid positivity as the fixed effects; baseline efficacy parameter and baseline age as covariates; and measures within-patient at each visit as a repeated measure. An unstructured variance-covariance matrix was used. The following factors may also have be included in the model: ApoE carrier status, baseline use of AD symptomatic medication and clinical subgroup - MCI or vmAD, if found to be significantly associated with the response measure (p < 0.15).

Outcome measures

Measure	Placebo Arm Part A n=62 Participants Subjects who received Placebo during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 vehicle without its active ingredient.	ABvac40 Arm Part A n=62 Participants Subjects who received ABvac40 during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 (containing 0.2 mg of Aβx-40).	ABvac40 Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with ABvac40 plus an ABvac40 booster shot after 6 months in Part B.	Placebo+Booster Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with placebo plus an ABvac40 booster shot at Visit 13 in Part B.
Level of p-Tau 181 in CSF Week 50A	2.43 pg/mL Standard Error 1.684	3.15 pg/mL Standard Error 1.697	—	—
Level of p-Tau 181 in CSF Week 104A	1.55 pg/mL Standard Error 2.387	0.82 pg/mL Standard Error 2.634	—	—

SECONDARY outcome

Timeframe: Part A (Week 50A and Week 104A)

Population: The Intent-to-treat (ITT) analysis set consisted of all subjects randomized who received any IMP. Analysis of all secondary efficacy endpoints was carried out using the ITT analysis set. Subjects were analyzed according to their randomized treatment assignment, regardless of the treatment received.

The change in levels of neurofilament light in cerebrospinal fluid (CSF) from baseline to each applicable post-baseline efficacy visit (Part A) was analyzed using a Mixed-Model Repeated Measures (MMRM), and the ITT analysis set.

The MMRM included change from baseline in the efficacy parameter as the dependent variable; treatment, protocol-specified visits, treatment-by-visit interaction, and amyloid positivity as the fixed effects; baseline efficacy parameter and baseline age as covariates; and measures within-patient at each visit as a repeated measure. An unstructured variance-covariance matrix was used. The following factors may also have be included in the model: ApoE carrier status, baseline use of AD symptomatic medication and clinical subgroup - MCI or vmAD, if found to be significantly associated with the response measure (p < 0.15).

Outcome measures

Measure	Placebo Arm Part A n=62 Participants Subjects who received Placebo during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 vehicle without its active ingredient.	ABvac40 Arm Part A n=62 Participants Subjects who received ABvac40 during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 (containing 0.2 mg of Aβx-40).	ABvac40 Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with ABvac40 plus an ABvac40 booster shot after 6 months in Part B.	Placebo+Booster Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with placebo plus an ABvac40 booster shot at Visit 13 in Part B.
Level of Neurofilament Light in CSF Week 50A	59.36 pg/mL Standard Error 76.513	181.20 pg/mL Standard Error 78.606	—	—
Level of Neurofilament Light in CSF Week 104A	317.11 pg/mL Standard Error 190.948	276.14 pg/mL Standard Error 216.781	—	—

SECONDARY outcome

Timeframe: Part A (Week 50A and Week 104A)

Population: The Intent-to-treat (ITT) analysis set consisted of all subjects randomized who received any IMP. Analysis of all secondary efficacy endpoints was carried out using the ITT analysis set. Subjects were analyzed according to their randomized treatment assignment, regardless of the treatment received.

The change in levels of neurogranin in cerebrospinal fluid (CSF) from baseline to each applicable post-baseline efficacy visit (Part A) was analyzed using a Mixed-Model Repeated Measures (MMRM), and the ITT analysis set.

The MMRM included change from baseline in the efficacy parameter as the dependent variable; treatment, protocol-specified visits, and treatment-by-visit interaction as the fixed effects; baseline efficacy parameter and baseline age as covariates; and measures within-patient at each visit as a repeated measure. An unstructured variance-covariance matrix was used. The following factors may also have be included in the model: ApoE carrier status, baseline use of AD symptomatic medication and clinical subgroup - MCI or vmAD, if found to be significantly associated with the response measure (p < 0.15).

Outcome measures

Measure	Placebo Arm Part A n=62 Participants Subjects who received Placebo during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 vehicle without its active ingredient.	ABvac40 Arm Part A n=62 Participants Subjects who received ABvac40 during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 (containing 0.2 mg of Aβx-40).	ABvac40 Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with ABvac40 plus an ABvac40 booster shot after 6 months in Part B.	Placebo+Booster Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with placebo plus an ABvac40 booster shot at Visit 13 in Part B.
Level of Neurogranin in CSF Week 50A	-4.69 pg/mL Standard Error 8.023	-5.93 pg/mL Standard Error 8.328	—	—
Level of Neurogranin in CSF Week 104A	-34.97 pg/mL Standard Error 13.533	-31.13 pg/mL Standard Error 15.571	—	—

SECONDARY outcome

Timeframe: Part A (baseline, and post-baseline at Week 24A, Week 50A, Week 77A, and Week 104A)

Population: The Intent-to-treat (ITT) analysis set consisted of all subjects randomized who received any IMP. Analysis of all secondary efficacy endpoints was carried out using the ITT analysis set. Subjects were analyzed according to their randomized treatment assignment, regardless of the treatment received.

The change in Mini Mental State Examination score (MMSE) score from baseline to each applicable post-baseline efficacy visit (Part A) was analyzed using a Mixed-Model Repeated Measures (MMRM), and the ITT analysis set.

MMSE is an 11-question measure that testes five areas of cognitive function: orientation, registration, attention and calculation, recall, and language. MMSE score ranges from 0 to 30, with lower scores indicating worst cognition.

Outcome measures

Measure	Placebo Arm Part A n=62 Participants Subjects who received Placebo during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 vehicle without its active ingredient.	ABvac40 Arm Part A n=62 Participants Subjects who received ABvac40 during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 (containing 0.2 mg of Aβx-40).	ABvac40 Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with ABvac40 plus an ABvac40 booster shot after 6 months in Part B.	Placebo+Booster Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with placebo plus an ABvac40 booster shot at Visit 13 in Part B.
Mini Mental State Examination Score Week 24A	-2.15 score on a scale Standard Error 0.422	-2.24 score on a scale Standard Error 0.420	—	—
Mini Mental State Examination Score Week 50A	-3.64 score on a scale Standard Error 0.465	-2.65 score on a scale Standard Error 0.460	—	—
Mini Mental State Examination Score Week 77A	-4.58 score on a scale Standard Error 0.628	-4.15 score on a scale Standard Error 0.621	—	—
Mini Mental State Examination Score Week 104A	-5.98 score on a scale Standard Error 0.816	-4.97 score on a scale Standard Error 0.816	—	—

SECONDARY outcome

Timeframe: Part A (Week 24A, Week 50A, Week 77A, and Week 104A)

Population: The Intent-to-treat (ITT) analysis set consisted of all subjects randomized who received any IMP. Analysis of all secondary efficacy endpoints was carried out using the ITT analysis set. Subjects were analyzed according to their randomized treatment assignment, regardless of the treatment received.

The change in clinical dementia rating-sum of boxes (CDR-SB) score from baseline to each applicable post-baseline efficacy visit (Part A) was analyzed using a Mixed-Model Repeated Measures (MMRM), and the ITT analysis set.

CDR-SB is a 5-point scale used to characterize six domains of cognitive and functional performance applicable to Alzheimer disease and related dementias: Memory, Orientation, Judgment & Problem Solving, Community Affairs, Home & Hobbies, and Personal Care. CDR-SB, derived as the sum of the six individual domain scores and can range from 0 to 18. The higher scores mean a worst outcome.

Outcome measures

Measure	Placebo Arm Part A n=62 Participants Subjects who received Placebo during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 vehicle without its active ingredient.	ABvac40 Arm Part A n=62 Participants Subjects who received ABvac40 during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 (containing 0.2 mg of Aβx-40).	ABvac40 Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with ABvac40 plus an ABvac40 booster shot after 6 months in Part B.	Placebo+Booster Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with placebo plus an ABvac40 booster shot at Visit 13 in Part B.
Clinical Dementia Rating-Sum of Boxes Score Week 24A	0.75 score on a scale Standard Error 0.152	0.73 score on a scale Standard Error 0.156	—	—
Clinical Dementia Rating-Sum of Boxes Score Week 50A	1.41 score on a scale Standard Error 0.222	1.36 score on a scale Standard Error 0.221	—	—
Clinical Dementia Rating-Sum of Boxes Score Week 77A	2.12 score on a scale Standard Error 0.328	2.05 score on a scale Standard Error 0.325	—	—
Clinical Dementia Rating-Sum of Boxes Score Week 104A	3.21 score on a scale Standard Error 0.463	2.90 score on a scale Standard Error 0.462	—	—

SECONDARY outcome

Timeframe: Part A (Week 24A, Week 50A, Week 77A, and Week 104A)

Population: The Intent-to-treat (ITT) analysis set consisted of all subjects randomized who received any IMP. Analysis of all secondary efficacy endpoints was carried out using the ITT analysis set. Subjects were analyzed according to their randomized treatment assignment, regardless of the treatment received.

The change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total score from baseline to each applicable post-baseline efficacy visit (Part A) was analyzed using a Mixed-Model Repeated Measures (MMRM), and the ITT analysis set.

RBANS assesses five cognitive domains, i.e., Immediate Memory, Visuospatial/constructional, Language, Attention, and Delayed Memory. The test consists of 12 subtests and the score on each subtest contributes to one of the five domains. Total score, which can range from 40 to 160, derived as the sum of the five domain scores. The higher scores mean a better outcome.

Outcome measures

Measure	Placebo Arm Part A n=62 Participants Subjects who received Placebo during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 vehicle without its active ingredient.	ABvac40 Arm Part A n=62 Participants Subjects who received ABvac40 during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 (containing 0.2 mg of Aβx-40).	ABvac40 Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with ABvac40 plus an ABvac40 booster shot after 6 months in Part B.	Placebo+Booster Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with placebo plus an ABvac40 booster shot at Visit 13 in Part B.
Repeatable Battery for the Assessment of Neuropsychological Status Score Week 24A	-1.30 score on a scale Standard Error 1.009	-2.10 score on a scale Standard Error 1.022	—	—
Repeatable Battery for the Assessment of Neuropsychological Status Score Week 50A	-5.45 score on a scale Standard Error 1.076	-5.56 score on a scale Standard Error 1.077	—	—
Repeatable Battery for the Assessment of Neuropsychological Status Score Week 77A	-4.71 score on a scale Standard Error 1.273	-2.66 score on a scale Standard Error 1.255	—	—
Repeatable Battery for the Assessment of Neuropsychological Status Score Week 104A	-3.17 score on a scale Standard Error 1.798	-1.33 score on a scale Standard Error 1.793	—	—

SECONDARY outcome

Timeframe: Part A (Week 24A, Week 50A, Week 77A, and Week 104A)

Population: The Intent-to-treat (ITT) analysis set consisted of all subjects randomized who received any IMP. Analysis of all secondary efficacy endpoints was carried out using the ITT analysis set. Subjects were analyzed according to their randomized treatment assignment, regardless of the treatment received.

The change in Alzheimer's Disease Cooperative Study - Activities of Daily Living, Mild Cognitive Impairment (ADCS-ADL MCI) total score from baseline to each applicable post-baseline efficacy visit (Part A) was analyzed using a Mixed-Model Repeated Measures (MMRM), and the ITT analysis set.

ADCS-ADL MCI is a 24-item scale that includes 6 basic activities of daily living (BADL) items and 16 instrumental activities of daily living (IADL) items that provide a total score from 0-78, with a lower score indicating greater severity.

Outcome measures

Measure	Placebo Arm Part A n=62 Participants Subjects who received Placebo during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 vehicle without its active ingredient.	ABvac40 Arm Part A n=62 Participants Subjects who received ABvac40 during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 (containing 0.2 mg of Aβx-40).	ABvac40 Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with ABvac40 plus an ABvac40 booster shot after 6 months in Part B.	Placebo+Booster Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with placebo plus an ABvac40 booster shot at Visit 13 in Part B.
Alzheimer's Disease Cooperative Study - Activities of Daily Living, Mild Cognitive Impairment Score Week 24A	-0.99 score on a scale Standard Error 0.834	-2.08 score on a scale Standard Error 0.844	—	—
Alzheimer's Disease Cooperative Study - Activities of Daily Living, Mild Cognitive Impairment Score Week 50A	-4.15 score on a scale Standard Error 1.124	-3.78 score on a scale Standard Error 1.112	—	—
Alzheimer's Disease Cooperative Study - Activities of Daily Living, Mild Cognitive Impairment Score Week 77A	-6.33 score on a scale Standard Error 1.399	-6.54 score on a scale Standard Error 1.380	—	—
Alzheimer's Disease Cooperative Study - Activities of Daily Living, Mild Cognitive Impairment Score Week 104A	-9.87 score on a scale Standard Error 2.002	-10.02 score on a scale Standard Error 1.982	—	—

SECONDARY outcome

Timeframe: Part A (Week 24A, Week 50A, Week 77A, and Week 104A)

Population: The Intent-to-treat (ITT) analysis set consisted of all subjects randomized who received any IMP. Analysis of all secondary efficacy endpoints was carried out using the ITT analysis set. Subjects were analyzed according to their randomized treatment assignment, regardless of the treatment received.

The change in Trail Making Test (TMT) scores (Trail A and Trail B) from baseline to each applicable post-baseline efficacy visit (Part A) was analyzed using a Mixed-Model Repeated Measures (MMRM), and the ITT analysis set.

TMT consists of two parts in which the patient is instructed to connect a set of 25 dots as quickly as possible while still maintaining accuracy. There are two parts to the test: in the first, the targets are all numbers from 1 to 25 and the test taker needs to connect them in sequential order; in the second part, the dots go from 1 to 13 and include letters from A to L. The lower timings mean a better outcome.

Outcome measures

Measure	Placebo Arm Part A n=62 Participants Subjects who received Placebo during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 vehicle without its active ingredient.	ABvac40 Arm Part A n=62 Participants Subjects who received ABvac40 during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 (containing 0.2 mg of Aβx-40).	ABvac40 Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with ABvac40 plus an ABvac40 booster shot after 6 months in Part B.	Placebo+Booster Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with placebo plus an ABvac40 booster shot at Visit 13 in Part B.
Trail Making Test Scores Week 24A - Trail A	0.54 seconds Standard Error 2.960	-0.59 seconds Standard Error 2.939	—	—
Trail Making Test Scores Week 50A - Trail A	11.34 seconds Standard Error 4.186	3.59 seconds Standard Error 4.023	—	—
Trail Making Test Scores Week 77A - Trail A	17.42 seconds Standard Error 4.669	2.79 seconds Standard Error 4.425	—	—
Trail Making Test Scores Week 104A - Trail A	20.09 seconds Standard Error 7.253	9.24 seconds Standard Error 6.967	—	—
Trail Making Test Scores Week 24A - Trail B	5.43 seconds Standard Error 8.102	-8.47 seconds Standard Error 8.464	—	—
Trail Making Test Scores Week 50A - Trail B	18.83 seconds Standard Error 8.503	18.43 seconds Standard Error 9.122	—	—
Trail Making Test Scores Week 77A - Trail B	17.13 seconds Standard Error 8.680	2.38 seconds Standard Error 9.762	—	—
Trail Making Test Scores Week 104A - Trail B	20.81 seconds Standard Error 10.715	-4.64 seconds Standard Error 11.206	—	—

SECONDARY outcome

Timeframe: Part A (Week 24A, Week 50A, and Week 104A)

Population: The Intent-to-treat (ITT) analysis set consisted of all subjects randomized who received any IMP. Analysis of all secondary efficacy endpoints was carried out using the ITT analysis set. Subjects were analyzed according to their randomized treatment assignment, regardless of the treatment received.

The change in Investigator Global Evaluation (IGE) score from baseline to each applicable post-baseline efficacy visit (Part A) was analyzed using a Mixed-Model Repeated Measures (MMRM), and the ITT analysis set.

IGE score range at baseline: 1-Good general status; 2-Slight deterioration; 3-Moderate deterioration; 4-Bad general status.

IGE score range after baseline: 1-Marked improvement; 2-Moderate improvement; 3-Slight improvement; 4-No change; 5-Slight worsening; 6-Moderate worsening; 7-Marked worsening.

Outcome measures

Measure	Placebo Arm Part A n=62 Participants Subjects who received Placebo during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 vehicle without its active ingredient.	ABvac40 Arm Part A n=62 Participants Subjects who received ABvac40 during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 (containing 0.2 mg of Aβx-40).	ABvac40 Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with ABvac40 plus an ABvac40 booster shot after 6 months in Part B.	Placebo+Booster Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with placebo plus an ABvac40 booster shot at Visit 13 in Part B.
Investigator Global Evaluation Score Week 104A	4.55 score on a scale Standard Error 0.180	4.45 score on a scale Standard Error 0.184	—	—
Investigator Global Evaluation Score Week 24A	4.02 score on a scale Standard Error 0.075	4.07 score on a scale Standard Error 0.077	—	—
Investigator Global Evaluation Score Week 50A	4.26 score on a scale Standard Error 0.101	4.21 score on a scale Standard Error 0.101	—	—

SECONDARY outcome

Timeframe: Part A (Week 24A, Week 50A, Week 77A, and Week 104A)

Population: The Intent-to-treat (ITT) analysis set consisted of all subjects randomized who received any IMP. Analysis of all secondary efficacy endpoints was carried out using the ITT analysis set. Subjects were analyzed according to their randomized treatment assignment, regardless of the treatment received. Number of participants entered in each row differs from the overall number of participants because data from all participants were not available at each visit.

Subjects with suicidal ideation or suicidal behavior since last visit.

Outcome measures

Measure	Placebo Arm Part A n=62 Participants Subjects who received Placebo during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 vehicle without its active ingredient.	ABvac40 Arm Part A n=62 Participants Subjects who received ABvac40 during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 (containing 0.2 mg of Aβx-40).	ABvac40 Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with ABvac40 plus an ABvac40 booster shot after 6 months in Part B.	Placebo+Booster Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with placebo plus an ABvac40 booster shot at Visit 13 in Part B.
Columbia Suicide Severity Rating Scale Week 104A - suicidal ideation	0 Participants	0 Participants	—	—
Columbia Suicide Severity Rating Scale Week 24A - suicidal ideation	1 Participants	1 Participants	—	—
Columbia Suicide Severity Rating Scale Week 24A - suicidal behavior	0 Participants	0 Participants	—	—
Columbia Suicide Severity Rating Scale Week 50A - suicidal ideation	1 Participants	2 Participants	—	—
Columbia Suicide Severity Rating Scale Week 50A - suicidal behavior	0 Participants	0 Participants	—	—
Columbia Suicide Severity Rating Scale Week 77A - suicidal ideation	1 Participants	4 Participants	—	—
Columbia Suicide Severity Rating Scale Week 77A - suicidal behavior	0 Participants	0 Participants	—	—
Columbia Suicide Severity Rating Scale Week 104A - suicidal behavior	0 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: Part A (Week 50A and Week 104A)

Population: The Intent-to-treat (ITT) analysis set consisted of all subjects randomized who received any IMP. Analysis of all secondary efficacy endpoints was carried out using the ITT analysis set. Subjects were analyzed according to their randomized treatment assignment, regardless of the treatment received.

The change in Euroqol 5 Dimensions 5 Levels (EQ-5D-5L) - overall severity index score from baseline to each applicable post-baseline efficacy visit (Part A) was analyzed using a Mixed-Model Repeated Measures (MMRM), and the ITT analysis set.

The EQ-5D-5L descriptive system comprises of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), with each dimension measured on the following increasing scale of severity: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems.

Outcome measures

Measure	Placebo Arm Part A n=62 Participants Subjects who received Placebo during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 vehicle without its active ingredient.	ABvac40 Arm Part A n=62 Participants Subjects who received ABvac40 during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 (containing 0.2 mg of Aβx-40).	ABvac40 Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with ABvac40 plus an ABvac40 booster shot after 6 months in Part B.	Placebo+Booster Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with placebo plus an ABvac40 booster shot at Visit 13 in Part B.
EuroQol 5 Dimensions 5 Levels Overall Severity Index Score Week 50A	-0.99 score on a scale Standard Error 1.204	-2.71 score on a scale Standard Error 1.196	—	—
EuroQol 5 Dimensions 5 Levels Overall Severity Index Score Week 104A	-3.06 score on a scale Standard Error 1.740	-0.92 score on a scale Standard Error 1.725	—	—

SECONDARY outcome

Timeframe: Part A (Week 50A and Week 104A)

Population: The Intent-to-treat (ITT) analysis set consisted of all subjects randomized who received any IMP. Analysis of all secondary efficacy endpoints was carried out using the ITT analysis set. Subjects were analyzed according to their randomized treatment assignment, regardless of the treatment received.

The change in Euroqol 5 Dimensions 5 levels (EQ-5D-5L) - visual analogue scale (VAS) score from baseline to each applicable post-baseline efficacy visit (Part A) was analyzed using a Mixed-Model Repeated Measures (MMRM), and the ITT analysis set.

VAS records the patient's self-rated health on a vertical scale, ranging from 100 = 'Best imaginable health state' down to 0 = 'Worst imaginable health state'.

Outcome measures

Measure	Placebo Arm Part A n=62 Participants Subjects who received Placebo during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 vehicle without its active ingredient.	ABvac40 Arm Part A n=62 Participants Subjects who received ABvac40 during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 (containing 0.2 mg of Aβx-40).	ABvac40 Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with ABvac40 plus an ABvac40 booster shot after 6 months in Part B.	Placebo+Booster Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with placebo plus an ABvac40 booster shot at Visit 13 in Part B.
EuroQol 5 Dimensions 5 Levels - Visual Analogue Scale Score Week 50A	-5.20 score on a scale Standard Error 2.335	-5.07 score on a scale Standard Error 2.289	—	—
EuroQol 5 Dimensions 5 Levels - Visual Analogue Scale Score Week 104A	-5.55 score on a scale Standard Error 3.109	-1.84 score on a scale Standard Error 3.111	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Part A (Baseline, and post-Baseline visits at Week 2A, Week 6A, Week 10A, Week 14A, Week 18A, Week 24A, Week 40A, Week 44A, Week 50A, Week 77A, and Week 104A)

Population: The Per-Protocol analysis set comprised all subjects in the ITT analysis set who received all doses of the IMP (on V1, V4, V7, V10, V13 and V18 in Part A), attended the safety visit after Booster (V20 in Part A) and had no major protocol deviations that could have affected the efficacy analyses.

Average maximal increment (MΔ) of plasma anti-Aβ40 antibody signal (optical density [OD] in ELISA) in each subject with regard to Baseline visit.

Sensitivity analyses in the PP (Part A) analysis set.

Outcome measures

Measure	Placebo Arm Part A n=45 Participants Subjects who received Placebo during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 vehicle without its active ingredient.	ABvac40 Arm Part A n=54 Participants Subjects who received ABvac40 during Part A. Six administrations: the first five administered once every 4 weeks (28±3 days) and the sixth at week 42 (Visit 18), 26 weeks after the fifth. Each administration consisted of 1 mL injection of ABvac40 (containing 0.2 mg of Aβx-40).	ABvac40 Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with ABvac40 plus an ABvac40 booster shot after 6 months in Part B.	Placebo+Booster Arm Part B Subjects received 5 monthly (every 4 weeks) immunizations with placebo plus an ABvac40 booster shot at Visit 13 in Part B.
Average Maximal Increment of Anti-Aβ40 Antibody Signal (Optical Density [OD] in ELISA) - Sensitivity	0.10 OD Standard Deviation 0.13	3.29 OD Standard Deviation 0.67	—	—

Adverse Events

Placebo Arm Part A

Serious events: 16 serious events

Other events: 53 other events

Deaths: 1 deaths

ABvac40 Arm Part A

Serious events: 17 serious events

Other events: 57 other events

Deaths: 1 deaths

ABvac40 Arm Part B

Serious events: 6 serious events

Other events: 30 other events

Deaths: 0 deaths

Placebo+Booster Arm Part B

Serious events: 2 serious events

Other events: 30 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo Arm Part A n=60 participants at risk Subjects received 5 monthly (every 4 weeks) immunizations with placebo plus a placebo booster shot in Part A.	ABvac40 Arm Part A n=64 participants at risk Subjects received 5 monthly (every 4 weeks) immunizations with ABvac40 plus an ABvac40 booster shot in Part A.	ABvac40 Arm Part B n=37 participants at risk Subjects received 5 monthly (every 4 weeks) immunizations with ABvac40 plus an ABvac40 booster shot after 6 months in Part B.	Placebo+Booster Arm Part B n=40 participants at risk Subjects received 5 monthly (every 4 weeks) immunizations with placebo plus an ABvac40 booster shot at Visit 13 in Part B.
Infections and infestations Coronavirus infection	0.00% 0/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	2.5% 1/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Infections and infestations Pneumonia bacterial	1.7% 1/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal cancer	0.00% 0/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	1.6% 1/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive lobular breast carcinoma	1.7% 1/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Nasal cavity cancer	1.7% 1/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic neoplasm	1.7% 1/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Injury, poisoning and procedural complications Femur fracture	0.00% 0/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	3.1% 2/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Injury, poisoning and procedural complications Humerus fracture	0.00% 0/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	1.6% 1/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Injury, poisoning and procedural complications Pelvic fracture	0.00% 0/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	2.7% 1/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Injury, poisoning and procedural complications Fall	1.7% 1/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Injury, poisoning and procedural complications Road traffic accident	1.7% 1/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Vascular disorders Peripheral artery stenosis	0.00% 0/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	1.6% 1/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Vascular disorders Venous thrombosis limb	0.00% 0/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	2.7% 1/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Cardiac disorders Acute myocardial infarction	0.00% 0/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	2.7% 1/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Cardiac disorders Atrial fibrillation	1.7% 1/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	2.7% 1/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Cardiac disorders Atrioventricular block complete	0.00% 0/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	2.7% 1/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Nervous system disorders Amyloid related imaging abnormalities	15.0% 9/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	12.5% 8/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	2.7% 1/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Nervous system disorders Cerebellar infarction	0.00% 0/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	1.6% 1/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Nervous system disorders Cerebral haemorrhage	1.7% 1/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Nervous system disorders Cerebral infarction	1.7% 1/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Nervous system disorders Lacunar infarction	0.00% 0/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	2.5% 1/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
General disorders Chest pain	0.00% 0/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	1.6% 1/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
General disorders General physical health deterioration	0.00% 0/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	1.6% 1/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	1.6% 1/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Gastrointestinal disorders Inguinal hernia	1.7% 1/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Hepatobiliary disorders Cholecystitis	0.00% 0/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	1.6% 1/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	4.7% 3/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Psychiatric disorders Agitation	1.7% 1/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.

Other adverse events

Measure	Placebo Arm Part A n=60 participants at risk Subjects received 5 monthly (every 4 weeks) immunizations with placebo plus a placebo booster shot in Part A.	ABvac40 Arm Part A n=64 participants at risk Subjects received 5 monthly (every 4 weeks) immunizations with ABvac40 plus an ABvac40 booster shot in Part A.	ABvac40 Arm Part B n=37 participants at risk Subjects received 5 monthly (every 4 weeks) immunizations with ABvac40 plus an ABvac40 booster shot after 6 months in Part B.	Placebo+Booster Arm Part B n=40 participants at risk Subjects received 5 monthly (every 4 weeks) immunizations with placebo plus an ABvac40 booster shot at Visit 13 in Part B.
Investigations Platelet count decreased	0.00% 0/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	5.0% 2/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Injury, poisoning and procedural complications Fall	6.7% 4/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	14.1% 9/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	10.0% 4/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Vascular disorders Hypertension	10.0% 6/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	4.7% 3/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Nervous system disorders Headache	11.7% 7/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	7.8% 5/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	8.1% 3/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	7.5% 3/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Nervous system disorders Dizziness	3.3% 2/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	4.7% 3/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	5.0% 2/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Nervous system disorders Loss of consciousness	0.00% 0/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	5.0% 2/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
General disorders Injection site erythema	6.7% 4/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	9.4% 6/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	8.1% 3/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	2.5% 1/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
General disorders Injection site reaction	6.7% 4/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	6.2% 4/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	10.8% 4/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	7.5% 3/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
General disorders Injection site swelling	1.7% 1/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	7.8% 5/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	5.4% 2/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	2.5% 1/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
General disorders Fatigue	6.7% 4/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	4.7% 3/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	5.4% 2/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	5.0% 2/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
General disorders Peripheral swelling	1.7% 1/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	1.6% 1/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	10.8% 4/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	2.5% 1/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
General disorders Inflammation	0.00% 0/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	4.7% 3/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	2.7% 1/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	5.0% 2/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
General disorders Injection site induration	1.7% 1/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	4.7% 3/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	2.7% 1/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	7.5% 3/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
General disorders Injection site pain	1.7% 1/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	3.1% 2/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	2.7% 1/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	7.5% 3/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Respiratory, thoracic and mediastinal disorders Cough	6.7% 4/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Skin and subcutaneous tissue disorders Erythema	11.7% 7/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	15.6% 10/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	8.1% 3/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Skin and subcutaneous tissue disorders Pruritus	1.7% 1/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	3.1% 2/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	8.1% 3/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Psychiatric disorders Anxiety	3.3% 2/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	6.2% 4/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	2.7% 1/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	2.5% 1/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Psychiatric disorders Irritability	1.7% 1/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	4.7% 3/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	5.0% 2/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Musculoskeletal and connective tissue disorders Back pain	5.0% 3/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	6.2% 4/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	5.0% 2/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	3.3% 2/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	3.1% 2/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	5.4% 2/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	5.0% 2/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Infections and infestations Urinary tract infection	5.0% 3/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	17.2% 11/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	13.5% 5/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	10.0% 4/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Infections and infestations Coronavirus infection	1.7% 1/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	6.2% 4/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	16.2% 6/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	22.5% 9/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Infections and infestations Periodontitis	0.00% 0/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	5.0% 2/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Infections and infestations Tooth infection	6.7% 4/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	2.5% 1/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Metabolism and nutrition disorders Iron deficiency	0.00% 0/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	2.7% 1/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	5.0% 2/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Metabolism and nutrition disorders Hyperglycaemia	1.7% 1/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	5.0% 2/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Blood and lymphatic system disorders Anaemia	3.3% 2/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	3.1% 2/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	5.4% 2/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Cardiac disorders Atrial fibrillation	0.00% 0/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	3.1% 2/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	5.4% 2/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Gastrointestinal disorders Vomiting	5.0% 3/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	3.1% 2/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	2.5% 1/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Psychiatric disorders Depression	5.0% 3/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	1.6% 1/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	8.1% 3/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Gastrointestinal disorders Constipation	0.00% 0/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	1.6% 1/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	5.4% 2/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Psychiatric disorders Insomnia	3.3% 2/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	1.6% 1/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	5.4% 2/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	2.5% 1/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Infections and infestations Bronchitis	3.3% 2/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	5.4% 2/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Gastrointestinal disorders Toothache	0.00% 0/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	5.4% 2/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Investigations Gamma-glutamyltransferase increased	5.0% 3/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.
Infections and infestations Influenza	5.0% 3/60 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/64 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/37 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.	0.00% 0/40 • Whole study duration (Part A+Part B; up to 42 months) AEs experienced by the subjects were collected throughout the whole study.

Additional Information

Maria Pascual Lucas

Araclon Biotech, S.L.

Phone: +34976796562

Email: mpascual@araclon.com

Results disclosure agreements

• Principal investigator is a sponsor employee Site may publish results from the Study, after providing Sponsor thirty days' notice prior to submitting a manuscript or other materials related to the Study to any outside party. At Sponsors' request, Site will remove any Confidential Information (other than Study results), and Site will upon Sponsors' request, delay publication or presentation for a period of up to one hundred twenty days to allow Sponsor to protect its interests in any Sponsor Inventions.
• Publication restrictions are in place

Restriction type: OTHER