A Randomized, Double-blind, Placebo-controlled, Parallel Group, Multicentre, Phase 2b Trial to Assess the Efficacy, Safety and Tolerability of AEF0217 for 24 Weeks in Adults and Older Adolescents With Down Syndrome.
The goal of this clinical trial is to identify if AEF0217 show an improvement in adaptive behaviors (daily life activities) in adults and older adolescents with Down Syndrome. It will also learn about the safety of AEF0217. The main questions it aims to answer are: * Does AEF0217 improve the daily life activities of the participants after being administered daily for 24 weeks ? * Does AEF0217 improve fluid cognitive function (cognitive abilities that do not depend on prior knowledge) and the crystallised one (knowledge acquired through one's culture, including verbal ability and social knowledge), the quality of life and sleep of the participants after being administered daily for 24 weeks ? * What medical problems do participants have when taking AEF0217? Researchers will compare 3 doses of AEF0217 to a placebo (a look-alike substance that contains no drug) to see if AEF0217 improves adaptative behaviours in people with Down Syndrome. Participants will: * Take AEF0217 or a placebo every day for 24 weeks * Visit the clinic 6 times with their caregiver for checkups, performing tests on a tablet and answering questionnaires. * Be called by phone at home 5 times to check that they are well.
• 1\. Male and female. For males: Throughout the trial and until the end of the trial, male participants should refrain from donating sperm and, if sexually active, use double-barrier contraceptive methods (i.e., male condoms and spermicide), or the female partner must use the same highly effective contraceptive methods as female trial participants .
∙ For females: Female participants of childbearing potential, defined as having a menstrual cycle that is confirmed prior to enrolment, must use highly effective contraception throughout the trial and until 3 months after the last dose of the trial intervention, be sexually abstinent, or have a vasectomized partner.
• 2\. Age ≥16 to ≤32years.
• 3\. BMI ≥18.0 and ≤35 kg/m2.
• 4\. Clinical diagnosis of Down syndrome (full trisomy 21 or translocations) documented by chromosomal analysis (karyotyping).
• 5\. Must be independently mobile and have sufficient vision and hearing to participate in the trial evaluations.
• 6\. IQ \>35-70 measured with Leiter-3. Individuals with IQ from \>35 to \<40 must have adequate cognitive and behavioural abilities according to the judgment of the principal investigator.
• 7\. VCI of WISC-V language test score \>4, based on mental age (estimated via IQ).
• 8.Must be able to understand most of the time and to express if he/she does not understand to the extent that he/she can accept the trial procedures. Must not use other forms of communication, signs, symbol boards, or devices as his/her primary form of communication.
• 9\. Must have a parent or other reliable caregiver who agrees to accompany the participant to all clinic visits, provide information about the participant as required by the protocol, and ensure compliance with the medication schedule and protocol requirements
• 10.The parent or caregiver must be a constant and reliable informant with sufficient contact with the participant to have detailed knowledge of the participant's adaptive functioning to be able to answer accurately the questions asked by a neuropsychologist at the assessments.
• 11\. Vital signs, ECG , and safety laboratory3 parameters must be without clinically relevant abnormalities as per the judgement of the investigator, except for:
‣ Stable type 1 or 2 diabetes provided the participant is monitored regularly prior to and during the trial to ensure adequate glucose control.
⁃ Hypothyroidism controlled by treatment so that the participant is euthyroid and T4 stable (range 77-155 nmol/L) for at least 6 weeks prior to randomization. Fluctuations in TSH up to a maximum of 10 mIU/L are allowed.
• 12\. a. Assent by the participant and consent by the legally authorized representative(s) on behalf of the participant or b. Consent by the participant in situations where consent rather than assent can be provided by the participant.
• 13\. Informed consent by the participant's caregiver to take on the obligations of the caregiver in this trial.