Safety, Tolerability and Immunogenicity of ACI-24 Vaccine in Adults With Down Syndrome

Inclusion Criteria

• Males or females with Down Syndrome aged ≥25 to ≤45 years, with a cytogenetic diagnosis being either Trisomy 21 or Complete Unbalanced Translocation of the Chromosome 21.
• Subjects and their study partner/legal representative in the opinion of the investigator able to understand and to provide written informed consent.
• Written informed consent obtained from subjects and their study partner/legal representative before any trial-related activities.
• In the opinion of the investigator able to fully participate in the trial and sufficiently proficient in English to be capable of reliably completing study assessments.
• Subjects have a study partner/legal representative who have direct contact with the subjects at least 10 hours per week and who can be asked questions about the subjects.

Exclusion Criteria

• Subjects weighing less than 40 kg.
• IQ less than 40 (as assessed by Kaufman Brief Intelligence Test, Second Edition (KBIT-2).
• In the investigators opinion, any clinically significant current psychiatric or neurologic illness, including a past illness with a risk of recurrence, other than Down syndrome.
• Any medical condition likely to significantly hamper the evaluation of safety of the study drug.
• DSM-IV criteria for drug or alcohol abuse or dependence currently met within the past five years.
• History or presence of uncontrolled seizures. If history of seizures, they must be well controlled with no occurrence of seizures in the past 2 years prior to study screening. The use of anti-epileptic medications is permitted.
• History of meningitis or meningoencephalitis.
• History of malignant neoplasms within 3 years prior to study screening or where there is current evidence of recurrent or metastatic disease.
• History of persistent cognitive deficits immediately following head trauma.
• History of inflammatory neurology disorders.
• History of autoimmune disease with potential for CNS involvement.
• MRI scan at screening showing a single area of cerebral vasogenic edema, superficial siderosis, or evidence of a prior macrohemorrhage, or showing more than four cerebral microhemorrhages (regardless of their anatomical location or diagnostic characterization as "possible" or "definite").
• MRI examination cannot be done for any reason, including metal implants contraindicated for MRI studies and/or severe claustrophobia.
• Significant hearing or visual impairment or other issues judged relevant by the investigator preventing to comply with the protocol and to perform the outcome measures.
• Severe infections or a major surgical operation within 3 months prior to screening.
• History of chronic or recurrent infections judged to be clinically significant by the investigator.
• History or presence of immunological or inflammatory conditions which are judged to be clinically significant by the investigator.
• Celiac disease not on a gluten free diet for at least 3 months prior to study screening.
• Chronic benign skin pathologies, unless viewed as clinically insignificant in the investigator's opinion.
• Any vaccine received within the past 2 months before baseline, except influenza vaccine which if indicated must be given at least 2 weeks prior to baseline.
• Clinically significant arrhythmias or other abnormalities on ECG at screening. (Minor abnormalities documented as clinically insignificant by the investigator will be allowed.)
• Clinically significant abnormal vital signs including sustained sitting blood pressure greater than 160/90 mmHg.
• In the opinion of the site investigator, deviations from normal values for hematologic parameters, liver function tests, and other biochemical measures, that are judged to be clinically significant.
• Subjects with treated hypothyroidism not on a stable dose of medication for at least 3 months prior to screening and having clinically significant abnormal serum T-4 and TSH at screening.
• Subjects with diabetes mellitus with an HbA1c of ≥ 8.0%.
• Subjects w