Safety, Tolerability and Immunogenicity of ACI-24 Vaccine in Adults With Down Syndrome
Condition: Down Syndrome
MeSH terms: Down Syndrome; Syndrome
Intervention: ACI-24 low dose; ACI-24 high dose; Placebo
Intervention description: ACI-24 administered as a sterile suspension in PBS via s.c. injection.; ACI-24 administered as a sterile suspension in PBS via s.c. injection.; Placebo is a standard PBS sterile solution administrated via s.c. injection.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 20.0
Sex: All
Minimum age: 25 Years
Maximum age: 45 Years
Healthy volunteers: No
Keywords: cognitive decline

Summary:

      The purpose of this study is to test in adults with Down Syndrome the safety, tolerability
      and immunogenicity of a vaccine, ACI-24.
    

Eligibility criteria:

        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.