Conditions
ACI-24-AD-DS-2102All conditions
Planned end date
31 Jul 2026 23:591. Prodromal AD: MCI due to AD according to National Institute on Aging-Alzheimer’s Association (NIA-AA) criteria.
2. PET scan at screening consistent with the presence of amyloid pathology.
3. Clinical Dementia Rating (CDR) -Global Score of 0.5.
4. Age ≥ 50 and ≤ 75 years at screening.
5. Subjects either not taking any marketed treatment for AD or receiving a stable dose of an acetylcholinesterase inhibitor and/or memantine for at least 2 months prior to baseline.
6.Subjects cared for by a reliable spouse or caregiver to assure compliance, assist with clinical assessments and report safety issues, and spouse or caregiver consents to serve in this role.
7. Subjects cared for by a reliable informant or caregiver to assure compliance, assist with clinical assessments and report safety issues.
8. Women must be post-menopausal for at least one year and/or surgically sterilized. Women 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 who in the opinion of the investigator are able to understand and to provide written informed consent.
10.Subjects and caregivers must be fluent 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:
11. Male or female subjects with DS with a cytogenetic diagnosis being either trisomy 21 or complete unbalanced translocation of the chromosome 21.
12. Age ≥ 35 and ≤ 50 years at screening.
13. Elevated brain Aβ as evidenced by amyloid PET-scan.
14. Subjects, their legal representatives (if applicable) and/or their study partners in the opinion of the investigator, are able to understand and to provide written informed consent before starting any study-related activities.
15. In the opinion of the investigator, subjects, their legal representatives (if applicable) and/or their study partners are able to fully participate in the study, be sufficiently proficient in the official languages(s) of the country they are living in, and be capable of reliably completing study assessments.
16. Women must be post-menopausal for at least one year and/or surgically sterilized. Women 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.
17. Mild to moderate intellectual disability as per Diagnostic and Statistical Manual of Mental Disorders (DSM-5) classification.
18. Subjects must have a study partner who has direct and regular contact with the subject and who is able to provide reliable answers to questions related to the subject, according to the study investigator.
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; treatment intake) and/or to have comorbidities preventing to complete 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 one 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 (e.g. head injury with loss of consciousness, symptomatic stroke, Parkinson’s disease, severe carotid occlusive disease, TIAs, haemorrhagic and/or non-haemorrhagic 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.
12. Severe infections or a major surgical operation within 3 months before screening.
13. History of chronic or recurrent infections judged to be clinically significant by the investigator and would potentially hamper the evaluation of efficacy and safety assessments.
14. History or presence of immunological or inflammatory conditions, including neurological disorders, judged to be clinically significant by the investigator.
15. History of severe allergic reaction (eg, anaphylaxis) including, but not limited to severe allergic reaction to previous vaccines, foods, and/or medications.
16. Clinically significant abnormal vital signs including sustained sitting blood pressure greater than 160/90 mm Hg.
17. Significant risk of suicide defined, using the Columbia-Suicide Severity Rating Scale, as the subject answering: “yes” to suicidal ideation questions 4 or 5 or answering: “yes” to suicidal behaviour within the past 12 months.
18. Clinically significant infections or major surgical operation within 3 months prior to screening. 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 or within 4 weeks after completion of the study.
20. Subjects with diabetes mellitus with haemoglobin A1c (HbA1c) levels of ≥ 8.0%.
21. When applicable, any contraindication for lumbar puncture.
22. Any contra-indication for PET-scan imaging.