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

This is a prospective multi-center, placebo controlled, double-blind and randomized dose
escalation study of 2 doses of ACI-24 versus Placebo over 24 months with a total of 21
visits.

All subjects will receive the study medication (ACI-24 or Placebo) 7 times via s.c. injection
(12 months) and will be followed up for 12 months after the last dose with a final safety and
efficacy assessment.

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 who have been receiving any experimental drug for Down Syndrome with a
washout less than 30 days or less than five halflives of the drug, whichever is
longer.

- Female subjects being pregnant as confirmed by serum testing at screening or planning
to be pregnant or lactating.

- Female subjects not using a reliable method of contraception (unless abstaining).

- Patient receiving any anticoagulant drug, or aspirin at doses greater than 100 mg
daily in the 7 days prior to lumbar puncture (in order to avoid risk of bleeding
during scheduled or unscheduled lumbar puncture)

- Use of antidepressants other than SSRI/SNRIs at stable dose, antipsychotics (typical
or atypical), GABA agonists (e.g. gabapentin), or stimulants (e.g. methylphenidate,
modafinil). In exceptional cases, low doses of atypical antipsychotics (e.g.
risperidone up to 0.5 mg/day or quetiapine up to 50 mg/day) or benzodiazepines are
only allowed after review by the site principal investigator, in consultation with the
project director and/or medical monitors.

- Current use of immunosuppressant or immunomodulating drugs or their use within the
past 6 months prior to study screening. Current use of steroids or their use within
the past 3 months prior to study screening.

- Use of Cholinesterase Inhibitor or use of Glutamatergic drugs (Topiramate, Memantine,
Lamotrigine) if not on stable dose for at least 3 months prior to screening.

- Subjects who have donated blood or blood products during the 30 days prior to
screening who plan to donate blood while participating in the study or within four
weeks after completion of the study.