Phase 2B Trial of AEF0217 in Participants with Down Syndrome

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Aelis Farma

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

11 Dec 2025 → ongoing

Decision date (initial)

2025-11-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AELIS FARMA · European Commission

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

Identify the endpoints and doses of AEF0217 administered for 24 weeks which show an improvement in adaptive behaviours compared to placebo, the dynamic of these effects and the influence of age group, degree of disability (moderate vs mild), APOE4 genotype and plasma concentrations of AEA and 2-AG at baseline.

Secondary objectives 5

1. Identify the endpoints and doses of AEF0217 administered for 24 weeks which show an improvement in fluid cognition compared to placebo, the dynamic of these effects and the influence of age group, degree of disability (moderate vs mild), APOE4 genotype and plasma concentrations of AEA and 2-AG at baseline.
2. Identify the endpoints and doses of AEF0217 administered for 24 weeks which show an improvement in crystallized cognition compared to placebo and the influence of age group, degree of disability (moderate vs mild), APOE4 genotype and plasma concentrations of AEA and 2-AG at baseline.
3. Identify the endpoints and doses of AEF0217 administered for 24 weeks which show an improvement in quality of life compared to placebo, the dynamic of these effects and the influence of age group, degree of disability (moderate vs mild), APOE4 genotype and plasma levels of AEA and 2-AG at baseline.
4. Identify the endpoints and doses of AEF0217 administered for 24 weeks which show an improvement in sleep compared to placebo, the dynamic of some of these effects and the influence of age group, degree of disability (moderate vs mild), APOE4 genotype and plasma levels of AEA and 2-AG at baseline.
5. To assess safety and tolerability of 24 weeks of treatment with AEF0217.

Conditions and MedDRA coding

Treatment of behavioural and cognitive impairments in Down syndrome.

Study design 4 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. 01. Male and female.
2. 02. Age ≥16 to ≤32years.
3. 03. BMI ≥18.0 and ≤35 kg/m2
4. 04. Clinical diagnosis of Down syndrome (full trisomy 21 and translocations) documented by chromosomal analysis (karyotyping).
5. 05. Must be independently mobile and have sufficient vision and hearing to participate in the trial evaluations.
6. 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.
7. 07. VCI of WISC-V language test score >4, based on mental age (estimated via IQ).
8. 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.
9. 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
10. 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. 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.

Exclusion criteria 19

1. 01. Pregnant or nursing female.
2. 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.
3. 11. Symptoms of early dementia confirmed by the NTG-EDSD
4. 12. Substance use disorder as defined by the DSM-5.
5. 14. Current diagnosis of epilepsy.
6. 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.
7. 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.
8. 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.
9. 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.
10. 23. Administration of an investigational medicinal product, including AEF0217, within the last 3 months prior to randomization.
11. 02. Mosaic Down syndrome or Down Syndrome Regression Disorder (DSRD).
12. 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.
13. 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
14. 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.
15. 06. Recent (≤1 year) or ongoing haematologic or oncologic disorders (mild anaemia is allowed).
16. 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.
17. 08. Clinically relevant unstable gastrointestinal, renal, hepatic, endocrine (including metabolic syndrome), or cardiovascular system disease as per the investigator’s judgement.
18. 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.
19. 16. Known hypersensitivity to AEF0217 or fructose intolerance.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 17

1. 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
2. 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 Secondary 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.
3. 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.
4. 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
5. 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.
6. 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.
7. 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): Changes 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
8. 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.
9. 10. The incidence of treatment-related and not related TEAEs will be tabulated by MedDRA SOC and PT and compared between treatment groups.
10. 11. TEAEs will be also summarized by severity (mild, moderate, severe) outcome and action taken with study drug.
11. 12. The incidence of treatment-emergent SAEs and related treatment emergent SAEs will be tabulated.
12. 13. Vital signs (cardiovascular and body temperature) from Day 1 to end of trial and over time,
13. 14. Clinical safety laboratory parameters (chemistry, haematology and urinalysis) from Day 1 to end of trial and over time,
14. 15. ECG from Day 1 to end of trial and over time.
15. 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.
16. 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).
17. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Aelis Farma

Sponsor organisation

Aelis Farma

Address

1 Rue Lafaurie De Monbadon

City

Bordeaux

Postcode

33000

Country

France

Scientific contact point

Organisation

Aelis Farma

Contact name

Chief Operating Officer

Public contact point

Organisation

Aelis Farma

Contact name

Chief Operating Officer

Locations

3 EU/EEA countries · 10 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 92 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications