NCT07334912

AEF0217 in Participants With Down Syndrome

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.

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 188 (estimated)
• Sponsor: Aelis Farma · Industry
• Sex: All
• Age: 16 Years – 32 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

This trial is a randomised, double blind, placebo controlled, parallel group, multicentre, Phase 2B trial. Approximately 188 participants will be enrolled at clinical centres in Spain, France and Italy. After the Day 1 visit (baseline) to the site and the Day 2 visit by phone/video, the trial will include 3 visits to the site during the treatment period, i.e., at the end of Weeks 4, 12, and 24, and there will be a follow-up visit 8 weeks after the end of treatment (in Week 32). Additional phone visits (via phone or video call) will be performed at the end of Weeks 1, 2, 8 and 18. Participants completing 24 weeks of treatment will be invited to enter an open label 12-month extension trial (OLE) when it is approved and, if choosing to do so, will continue directly into the extension trial. . The participants who do not choose to enter the extension trial will enter the follow-up period. The participants that complete the trial, before the extension trial starts, may enter when it starts. Safety assessments will be performed at each visit to the clinical site and include blood sampling for clinical chemistry, haematology and determination of AEF0217 and endocannabinoids concentrations at Weeks 12 and 24. In addition, urine samples will be collected. Efficacy assessments will be performed during treatment at the end of Week 4 (adaptive behaviours, cognition and sleep efficiency), Week 12 (adaptive behaviours, cognition, quality of life, sleep efficiency and clinician functional assessment ), Week 24 (adaptive behaviours, cognition, quality of life, clinician functional assessment and sleep) and Week 32 at the end of the follow-up period (adaptive behaviours, cognition, sleep efficiency and clinician functional assessment) only for the participants who enter the follow-up period. The total duration of the trial for an individual participant will be up to 36 weeks. An independent (from the sponsor and the investigational centres) safety data monitoring committee (IDMC) will be set up in charge of performing an independent interim safety analysis at a minimum after 40 participants (at a minimum) have been treated for 12 weeks. The membership (including physicians with experience with Down syndrome and clinical pharmacologists), role and responsibilities of the IDMC will be defined in a specific charter before the trial starts. The IDMC will make recommendations related to any potential safety issues/signals to the Steering Committee of the trial (i.e., the coordinating investigator, the principal site investigator and responsible physician in each site and sponsor representatives The trial will be conducted in accordance with the Declaration of Helsinki and ICH Good Clinical Practice. Before initiating the trial, the clinical trial protocol, the written participant information and informed consent forms, the investigator's brochure, the recruitment material, and any other information for the participants and caregivers will be submitted to and approved by central ethic committees and national health authorities, as applicable. Main Statistic analysis: For the primary endpoint descriptive analysis will include: 1. The raw scores of the 9 subdomains of the VABS 3; 2. The raw scores of the 9 subdomains standardized to 100; and 3. Change from baseline to Week 24. These variables will be presented by treatment, dose, and visit (baseline and 24 weeks). An MMRM will be used to evaluate the primary endpoint. The model will contain as dependent variable the change from baseline to Week 24 of the raw scores of the 9 subdomains of the VABS 3 standardized to 100 and as factors: 1. Treatment (placebo, AEF0217) 2. Dose (0 \[placebo\], 0.1, 0.2, 0.6 mg AEF0217) nested to treatment 3. Subdomains: receptive, expressive, written, personal, community, domestic, interpersonal relationships, play and leisure time, coping skills 4. Level of impairment at baseline 5. Treatment interactions with subdomain and/or level of impairment at baseline. 6. Dose interactions with subdomain and/or level of impairment at baseline The model will use a restricted maximum likelihood (REML) method, and an unstructured covariance matrix will be used. If the model is not estimable, a compound symmetry structure will be used instead. The primary endpoint will be reached if there is a statistically significant (p\<0.05) main effect of treatment or dose or any significant (p\<0.05) interactions between treatment or dose and subdomain and/or the previous factors with the impairment at baseline. For the other efficacy endpoints (secondary and exploratory) and pharmacodynamic endpoints the same model with the appropriate adaptations will be used as will be described in the SAP. Safety endpoints: TEAEs will be reported in individual data listings and frequency tables. Based on reported terms, TEAEs will be coded in and tabulated by MedDRA SOC and PT. AEs will be classified based on severity (mild, moderate, severe) and causality (related or not related) and outcome. Summary statistics of vital signs, ECG, and safety laboratory parameters (with flagging of values outside the normal ranges and considered clinically significant) will be provided.

Conditions

• Down Syndrome (Trisomy 21)

Interventions

Type	Name	Description
DRUG	AEF0217 100 µg	Sachet of granules
DRUG	AEF0217 300 µg	sachet of granules
DRUG	Placebo	sachet of matching placebo granules

Timeline

• Start date: 2025-12-22
• Primary completion: 2027-12-31
• Completion: 2027-12-31
• First posted: 2026-01-12
• Last updated: 2026-04-08

Locations

10 sites across 3 countries: France, Italy, Spain