AEF0217 in Participants With Down Syndrome

Exclusion Criteria23

• \. Pregnant or nursing female. Down syndrome
• \. Mosaic Down syndrome or Down Syndrome Regression Disorder (DSRD). Medical history and clinical status
• \. Active or clinically relevant conditions that could, in the investigator's judgment, affect absorption, distribution, or metabolism of the trial medication (e.g., inflammatory bowel disease, gastric or duodenal ulcers or severe lactose intolerance); controlled celiac disease is allowed.
• \. Clinically relevant obstructive pulmonary disease or asthma that is untreated. Patients well-controlled by treatment (inhalation or oral) for at least 6 weeks prior to screening may be included if considered safe by the investigator.
• \. Known severe obstructive sleep apnoea or if the investigator thinks that the person should be referred for a diagnosis/treatment of obstructive sleep apnoea.
• \. Recent (≤1 year) or ongoing haematologic or oncologic disorders (mild anaemia is allowed).
• \. History of infantile spasms/convulsions/epilepsy, severe head trauma or central nervous system infections (e.g., meningitis), except for isolated events of febrile seizures more than 8 years ago.
• \. Clinically relevant unstable gastrointestinal, renal, hepatic, endocrine (including metabolic syndrome), or cardiovascular system disease as per the investigator's judgement.
• \. Any prevailing psychiatric disorder diagnosed using the DSM-5 that dominates a person's overall clinical condition outside of Down syndrome. If symptoms consistent with a diagnosis of psychiatric illness are detected during the screening assessment (NPI-Q) and considered as dominating, the investigator may request a psychiatric evaluation. If necessary, a consultant psychiatrist will be responsible for the final diagnosis, as this is not the investigator's responsibility.
• \. Participants with secondary psychiatric disorders including conduct disorders, attention deficit hyperactivity disorder, depressive disorders, anxiety disorders, and others that: 1) dominate the overall clinical condition according to the investigator's assessment; and/or 2) are not stabilized by medical or behavioural treatments, a stabilized treatment being defined as a stable therapeutic regimen and dose for the 3 months prior to randomization; and/or 3) the type of pharmacological treatment is on the list of drugs that are prohibited.
• \. Symptoms of early dementia confirmed by the NTG-EDSD.
• \. Substance use disorder as defined by the DSM-5.
• \. Positive urine test for alcohol and drugs of abuse at screening and prior to first dosing.
• \. Current diagnosis of epilepsy.
• \. A history of intentional self-harm or suicide attempts brought on by suicidal thoughts. Suicidal ideation in the 12 months before screening, even if there was no suicide attempt or intentional self-harm. Assessed using 3 distinct questions about suicidal behaviour, suicidal ideation, and any self-harming actions.
• \. Known hypersensitivity to AEF0217 or fructose intolerance.
• \. Clinically significant illness, such as active infections, within 2 weeks prior to randomization, according to the investigator's judgment.
• \. Any current life-threatening disease.
• \. Any additional clinically significant concomitant disease, condition, or screening result that, in the investigator's opinion, could endanger the participant's safety, interfere with trial conduct and related procedures, or influence how the trial results are interpreted.
• \. Treatment with 1st generation neuroleptic drugs currently or within 3 months prior to randomization and benzodiazepines currently or in the 4 weeks prior to baseline assessments.
• \. Intake of products containing EGCG (e.g., TEAVIGO, Mega Green Tea Capsules Life Extension, or Font-UP Grand Fontaine Laboratories) currently or during the last 4 weeks prior to the baseline assessments.
• \. Treatment with medications or very regular consumption of fruits (i.e., pomelo/grapefruit) or natural remedies (i.e., hypericum preparations) known to strongly or moderately induce or inhibit CYP3A4/5 P450 isozymes..
• \. Administration of an investigational medicinal product, including AEF0217, within the last 3 months prior to randomization.