1-((3S,8S,9S,10R,13S,14S,17S)3-BENZYLOXY-10,13,17-TRIMETHYL-2,3,4,7,8,9,10,11,12,13,14,15,16,17-TETRADECAHYDRO-1HCYCLOPENTA[A]PHENANTHRENE-17-YL)ETHAN-1-ONE for Down syndrome

Inclusion criteria

• {"criterion_text":"- 01. Male and female.\n- 02. Age ≥16 to ≤32years.\n- 03. BMI ≥18.0 and ≤35 kg/m2\n- 04. Clinical diagnosis of Down syndrome (full trisomy 21 and translocations) documented by chromosomal analysis (karyotyping).\n- 05. Must be independently mobile and have sufficient vision and hearing to participate in the trial evaluations.\n- 06. 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.\n- 07. VCI of WISC-V language test score >4, based on mental age (estimated via IQ).\n- 08. 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.\n- 09. 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\n- 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.\n- 11. Vital signs, ECG , and safety laboratory3 parameters must be without clinically relevant abnormalities as per the judgement of the investigator, except for: -\tStable type 1 or 2 diabetes provided the participant is monitored regularly prior to and during the trial to ensure adequate glucose control. -\tHypothyroidism 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."}

Exclusion criteria

• {"criterion_text":"- 01. Pregnant or nursing female.\n- 23. Administration of an investigational medicinal product, including AEF0217, within the last 3 months prior to randomization.\n- 02. Mosaic Down syndrome or Down Syndrome Regression Disorder (DSRD).\n- 03. 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.\n- 04. 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\n- 05. Known severe obstructive sleep apnoea or if the investigator thinks that the person should be referred for a diagnosis/treatment of obstructive sleep apnoea.\n- 06. Recent (≤1 year) or ongoing haematologic or oncologic disorders (mild anaemia is allowed).\n- 07. 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.\n- 08. Clinically relevant unstable gastrointestinal, renal, hepatic, endocrine (including metabolic syndrome), or cardiovascular system disease as per the investigator’s judgement.\n- 09. 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.\n- 16. Known hypersensitivity to AEF0217 or fructose intolerance.\n- 10. 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.\n- 11. Symptoms of early dementia confirmed by the NTG-EDSD\n- 12. Substance use disorder as defined by the DSM-5.\n- 14. Current diagnosis of epilepsy.\n- 15. 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.\n- 20. 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.\n- 21. 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.\n- 22. 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."}

Primary endpoints

• {"endpoint_text":"- Normalized raw scores of the 9 subdomains of the VABS-3: Change from baseline to end of Week 24 (end of treatment) of the normalized 9 subdomains of the VABS-3.","definition_or_measurement_approach":"Change from baseline to end of Week 24 (end of treatment) in normalized raw scores of the 9 subdomains of the Vineland Adaptive Behavior Scales, 3rd Edition (VABS-3)."}

Secondary endpoints

• {"endpoint_text":"- 01. The fluid cognition composite change sensitive score of the NIH-ToolBox for ID: Changes from baseline to the end of Week 24 (end of treatment) in the fluid cognition composite change sensitive score of the NIH-TCB for ID","definition_or_measurement_approach":"Change from baseline to end of Week 24 in the fluid cognition composite change sensitive score of the NIH Toolbox for intellectual disability."}
• {"endpoint_text":"- 02. The 5 individual scores of the tests used to measure the fluid cognition composite change sensitive score in the NIH-TCB for ID o\tSecondary endpoint: Changes from baseline to end of Week 24 (end of treatment) in the 5 individual change sensitive scores of the tests used to measure fluid cognition in the NIH-TCB for ID.","definition_or_measurement_approach":"Changes from baseline to end of Week 24 in each of the five individual change-sensitive scores that comprise the NIH-TCB fluid cognition composite."}
• {"endpoint_text":"- 03. VCI of the WISC-V : Changes from screening values used as baseline to the end of Week 24 (end of treatment) of the VCI of the WISC-V.","definition_or_measurement_approach":"Change from screening (baseline) to end of Week 24 in the Verbal Comprehension Index (VCI) of the WISC-V."}
• {"endpoint_text":"- 04. Normalized scores of the 2 individual tests (vocabulary and similarities) comprising the VCI of the WISC-V Changes from screening values used as baseline to the end of Week 24 (end of treatment) in the 2 individual tests (vocabulary and similarities) comprising the VCI from the WISC-V","definition_or_measurement_approach":"Changes from screening to end of Week 24 in normalized scores for the vocabulary and similarities subtests composing the WISC-V VCI."}
• {"endpoint_text":"- 05. Total score of each scale of the Peds-QL 1. Generic Core scale; 2. Cognitive Functioning scale; 3. Impact Family Questionnaire : Changes from baseline to the end of Week 24 (end of treatment) of the total score of each scale of the Peds-QL.","definition_or_measurement_approach":"Change from baseline to end of Week 24 in total scores for each listed Peds-QL scales (Generic Core, Cognitive Functioning, Family Impact)."}
• {"endpoint_text":"- 06. Summary scores of the different dimensions of the Peds-QL: 1. Psychosocial Health; 2. Physical Health; 3. Parent HRQL; 4. Family Functioning: Changes from baseline to end of Week 24 (end of treatment) of each summary scores of the different dimensions of the Peds-QL.","definition_or_measurement_approach":"Change from baseline to end of Week 24 in each summary score dimension of the Peds-QL."}
• {"endpoint_text":"- 07. Normalized mean scale scores of the domains of the Peds-QL scales containing domains: 1. Generic Core scale (4 domains); 2. Impact Family Questionnaire (8 domains):\tChanges from baseline to end of Week 24 (end of treatment) of each mean scale scores of the different domains of the 2 scales of the Peds-QL containing domains, analysed by scale after normalisation to 100","definition_or_measurement_approach":"Changes from baseline to end of Week 24 in normalized mean domain scores of indicated Peds-QL scales, analysed by scale after normalization to 100."}
• {"endpoint_text":"- 09. The number of participants reporting a TEAE (n), the percentage of participants with an event (%), and the number of events reported (AEs and TEAEs) will be presented by treatment groups.","definition_or_measurement_approach":"Tabulation by treatment group of number and percentage of participants reporting TEAEs and number of events (AEs and TEAEs)."}
• {"endpoint_text":"- 10. The incidence of treatment-related and not related TEAEs will be tabulated by MedDRA SOC and PT and compared between treatment groups.","definition_or_measurement_approach":"Incidence of treatment-related and unrelated TEAEs tabulated by MedDRA System Organ Class and Preferred Term and compared between groups."}
• {"endpoint_text":"- 11. TEAEs will be also summarized by severity (mild, moderate, severe) outcome and action taken with study drug.","definition_or_measurement_approach":"Summary of TEAEs by severity, outcome and action taken with study drug."}
• {"endpoint_text":"- 12. The incidence of treatment-emergent SAEs and related treatment emergent SAEs will be tabulated.","definition_or_measurement_approach":"Tabulation of incidence of treatment-emergent SAEs and treatment-emergent SAEs related to treatment."}
• {"endpoint_text":"- 13. Vital signs (cardiovascular and body temperature) from Day 1 to end of trial and over time,","definition_or_measurement_approach":"Collection and analysis of vital signs from Day 1 through end of trial over time."}
• {"endpoint_text":"- 14. Clinical safety laboratory parameters (chemistry, haematology and urinalysis) from Day 1 to end of trial and over time,","definition_or_measurement_approach":"Serial clinical safety laboratory assessments (chemistry, haematology, urinalysis) from Day 1 through end of trial."}
• {"endpoint_text":"- 15. ECG from Day 1 to end of trial and over time.","definition_or_measurement_approach":"Serial ECG assessments from Day 1 through end of trial."}
• {"endpoint_text":"- 16. Changes from baseline at the end of Week 24 (end of treatment) and end of Week 32 (end of trial) in the total score of the ADAMS.","definition_or_measurement_approach":"Changes from baseline to Week 24 and Week 32 in total score of ADAMS (anxiety, depression and mood scale)."}
• {"endpoint_text":"- 17. Changes from baseline at the end of Week 24 (end of treatment) and end of Week 32 in the scores of each of the 5 subscales (maniac/hyperactive behaviour; depressed mood; social avoidance; general anxiety; and compulsive behaviour).","definition_or_measurement_approach":"Changes from baseline to Week 24 and Week 32 in each ADAMS subscale score (listed subscales)."}
• {"endpoint_text":"- 08. Sleep efficiency score of the PSQI : Changes from baseline to the end of Week 24 (end of treatment) for the sleep efficiency score of the PSQI.","definition_or_measurement_approach":"Change from baseline to end of Week 24 in PSQI sleep efficiency score."}

Methods

• Country-specific recruitment materials and arrangements documented (documents: K1/K2 recruitment materials and participant family leaflets).
• Use of family leaflets and participant information materials targeted at participants and caregivers (documents in FRA/ITA/SPA and CAT).
• Use of social media materials and email summaries for recruitment (document names include 'K2_Material for social media' and 'K2_Resumen para enviar por email').
• Videoscripts for participant information (video script documents present) for participant-facing recruitment/consent information.

France

Earliest CTIS Part Ii Submission Date

03-10-2025

Latest Decision Or Authorization Date

17-11-2025

Processing Time Days

45

Number Of Sites

5

Number Of Participants

80

Italy

Earliest CTIS Part Ii Submission Date

17-10-2025

Latest Decision Or Authorization Date

17-11-2025

Processing Time Days

31

Number Of Sites

3

Number Of Participants

58

Spain

Earliest CTIS Part Ii Submission Date

13-10-2025

Latest Decision Or Authorization Date

17-11-2025

Processing Time Days

35

Number Of Sites

2

Number Of Participants

50

Primary sponsor

Full Name

Aelis Farma

Organisation Type

Pharmaceutical company

Country Of Registered Address

France

Third parties

• {"country":"","full_name":"AELIS FARMA","duties_or_roles":"Monetary support","organisation_type":""}
• {"country":"","full_name":"European Commission","duties_or_roles":"Monetary support","organisation_type":""}