Inclusion Criteria:
Study Part 1
1. Age ≥50 and ≤85 years at screening.
2. Diagnosis of prodromal AD: MCI due to AD according to National Institute on
Aging-Alzheimer’s Association (NIA-AA) criteria.
3. PET scan at screening consistent with the presence of amyloid pathology.
4. Clinical Dementia Rating (CDR)-Global Score of 0.5.
5. Subjects who in the opinion of the investigator are able to understand the details of the
study and to provide written informed consent.
6. Subjects either not taking any marketed treatment for AD or receiving a stable dose of an
acetylcholinesterase inhibitor (ACHEI) and/or memantine for at least 2 months prior to
baseline.
7. Subjects cared for by a reliable spouse, informant, or study partner to assure compliance,
assist with clinical assessments, and report safety issues, and spouse, informant or study
partner consents to serve in this role.
8. Females who are either post-menopausal for at least 1 year and/or surgically sterilized, or
females of childbearing potential or not post-menopausal must have a negative blood
pregnancy test at screening and be willing to use highly effective methods of contraception
from the screening visit until the end of their participation. Male participants in the trial with
female partners of childbearing potential are required to use barrier methods of
contraception (condoms with spermicide) in addition to contraceptive measures used by
female partners during the whole study duration.
9. Subjects and study partners must be sufficiently proficient in the official language(s) of the
country they are living in and able to comply with all study procedures, including lumbar
punctures.

 

Study Part 2
1. Age ≥35 and ≤50 years at screening (subjects with DS with age ≥35 and ≤39 years may
be considered on the condition that there is prior evidence of amyloid results compatible
with AD pathology at PET-scan and/or in biofluids).
2. Male or female subjects with DS with a cytogenetic diagnosis being either trisomy 21 or
complete unbalanced translocation of the chromosome 21.
3. PET scan at screening consistent with the presence of amyloid pathology.
4. Subjects, their legal representatives (if applicable) and/or their study partners, in the
opinion of the investigator, are able to understand the details of the study and to provide
written informed consent before starting any study-related activities.
5. In the opinion of the investigator, subjects, their legal representatives (if applicable), and/or
their study partners or informants are able to fully participate in the study, are sufficiently
proficient in the official languages(s) of the country they are living in, and are capable of
reliably completing study assessments.
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6. Females who are either post-menopausal for at least 1 year and/or surgically sterilized, or
females of childbearing potential or not post-menopausal must have a negative blood
pregnancy test at screening and be willing to use highly effective methods of contraception
from the screening visit until the end of their participation. Male participants in the trial with
female partners of childbearing potential are required to use barrier methods of
contraception (condoms with spermicide) in addition to contraceptive measures used by
female partners during the whole study duration.
7. Mild to moderate intellectual disability as per Diagnostic and Statistical Manual of Mental
Disorders (DSM-5) classification.
8. Subjects must have a study partner who has direct and regular contact, at least 10 hours
per week, with the subject and who is able to provide reliable answers to questions related
to the subject, according to the study investigator.

 

Exclusion Criteria:
Study Part 1 and Part 2
Comorbidities
1. Any unstable and/or clinically significant medical condition likely to hamper the evaluation
of safety and/or efficacy of the study vaccine (eg, moderate and/or severe untreated
obstructive sleep apnea, clinically significant reduction in serum B12 or folate levels,
clinically significant abnormalities of thyroid function, stroke, or other cerebrovascular
conditions), as per investigator’s judgement.
2. Subjects considered to be unable to be compliant with study-related activities
(eg, completion of any study exams and assessments, respect of visit schedule and/or
treatment administration) and/or to have comorbidities preventing the completion of any
study exams and assessments (eg, significant hearing or visual impairments or other
disabilities) according to the investigator.
3. DSM-5 criteria for drug or alcohol abuse or dependence currently met within the past
5 years.
4. History or presence of uncontrolled seizures. If history of seizures, they must be well
controlled with no occurrence of seizures in the 2 years before study screening. The use
of antiepileptic medications is permitted.
5. Clinically significant arrhythmias or other clinically significant abnormalities on ECG at
screening.
6. Myocardial infarction within 1 year prior to baseline, unstable angina pectoris, or significant
coronary artery disease.
7. Concomitant or past history psychiatric or neurologic disorder other than those considered
to be related to AD (eg, head injury with loss of consciousness, symptomatic stroke,
Parkinson’s disease, severe carotid occlusive disease, transient ischemic attacks [TIAs],
hemorrhagic and/or non-hemorrhagic stroke).
8. History of meningitis or meningoencephalitis.
9. History of moderate or severe traumatic brain injury.
10. History of inflammatory neurological disorders.
11. History of cancer within the past 5 years other than treated squamous cell carcinoma,
basal cell carcinoma and melanoma in-situ, in-situ prostate cancer, or in-situ breast cancer
which have been fully removed and are considered cured.
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12. History of chronic or recurrent infections judged to be clinically significant by the
investigator and which would potentially hamper the evaluation of efficacy and safety
assessments.
13. History or presence of immunological or inflammatory conditions, including neurological
disorders, judged to be clinically significant by the investigator.
14. History of severe allergic reaction (eg, anaphylaxis) including, but not limited to severe
allergic reaction to previous vaccines, foods, and/or medications.
15. Clinically significant abnormal vital signs including sustained sitting blood pressure
>160/90 mm Hg.
16. Significant risk of suicide, defined using the C-SSRS as the subject answering “yes” to
suicidal ideation questions 4 or 5 or answering “yes” to suicidal behavior within the past
12 months.
17. Clinically significant infections or major surgical operation within 3 months prior to
screening.
18. Planned surgery anticipated to occur during participation in the study must be reviewed
and approved by the medical monitor at screening.
19. Subjects who have donated blood or blood products in the 30 days before screening or
who plan to donate blood while participating in the study.
20. Subjects with clinically uncontrolled diabetes mellitus and/or with hemoglobin A1c levels
of ≥8.0 %