AEF0217 in Participants With Down Syndrome

NCT07334912 | Recruiting Phase 2 DMC

• 2 other identifiers: AEF0217-2012025-521013-10-00
• Study Type: interventional
• Target: 188
• Locations: 3 countries
• Sites: 10

Brief 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.

Conditions

Down Syndrome (Trisomy 21)

Keywords

Down Syndrome; Trisomy 21; adaptative behaviour; cognitive impairments

Outcome Measures

Primary Outcomes (1)

• Change from baseline of the normalized scores of the 9 subdomains of the VABS-3 at week 24 (end of treatment)

  Raw scores will be normalised to 100. Higher scores on the VABS-3 indicate better adaptive functioning.

  Baseline and Week 24

Secondary Outcomes (35)

• Changes from baseline in the fluid cognition composite change sensitive score of the NIH-ToolBox for Intellectual Deficiencies at Week 24 (end of treatment)

  Baseline and Week 24

• Changes from baseline in the individual change sensitive scores of the Flanker inhibitory control & attention test used to measure fluid cognition in the NIH-TB for ID at week 24 (End of treatment).

  Baseline and Week 24

• Changes from baseline in the individual change sensitive scores of the Picture Sequence Memory test used to measure fluid cognition in the NIH-TB for ID at week 24 (End of treatment).

  Baseline and Week 24

• Changes from baseline in the individual change sensitive scores of the List Sorting Working Memory test used to measure fluid cognition in the NIH-TB for ID at week 24 (End of treatment).

  Baseline and Week 24

• Changes from baseline in the individual change sensitive scores of the Dimensional Change Card Sort test used to measure fluid cognition in the NIH-TB for ID at week 24 (End of treatment).

  Baseline and Week 24

Study Arms (4)

AEF0217 0.1 mg

EXPERIMENTAL

1 sachet of AEF0217 100µg + 1 sachet of Placebo

Drug: AEF0217 100 µg; Drug: Placebo

AEF0217 0.2 mg

EXPERIMENTAL

2 sachets of AEF0217 100µg

Drug: AEF0217 100 µg

AEF0217 0.6 mg

EXPERIMENTAL

2 sachets of AEF0217 300µg

Drug: AEF0217 300 µg

Placebo

PLACEBO COMPARATOR

2 sachets of placebo

Drug: Placebo

Interventions

AEF0217 100 µg DRUG

Sachet of granules

Also known as: 3β-benzyloxy-17α-methyl-pregn-5-en-20-one

AEF0217 0.1 mg; AEF0217 0.2 mg

AEF0217 300 µg DRUG

sachet of granules

Also known as: 3β-benzyloxy-17α-methyl-pregn-5-en-20-one

AEF0217 0.6 mg

Placebo DRUG

sachet of matching placebo granules

AEF0217 0.1 mg; Placebo

Eligibility Criteria

• Age: 16 Years - 32 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• \. 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.
• \. Age ≥16 to ≤32years.
• \. BMI ≥18.0 and ≤35 kg/m2.
• \. Clinical diagnosis of Down syndrome (full trisomy 21 or translocations) documented by chromosomal analysis (karyotyping).
• \. Must be independently mobile and have sufficient vision and hearing to participate in the trial evaluations.
• \. 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.
• \. VCI of WISC-V language test score \>4, based on mental age (estimated via IQ).
• 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.
• \. 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
• 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.
• \. 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.
• \. 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.

You may not qualify if:

• \. 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.

Sponsors & Collaborators

• Aelis Farma: lead
• European Commission: collaborator
• BioClever 2005 S.L.: collaborator
• Eurofins ADME, S.L.: collaborator
• Pharmalex: collaborator
• Hospital del Mar Research Institute (IMIM): collaborator

Study Sites (10)

CHU de Bordeaux

Bordeaux, 33000, France

NOT YET RECRUITING

Genetics department, Hospices Civils de Lyon

Lyon, 69500, France

NOT YET RECRUITING

Service Génétique Médicale, CHU de Montpellier

Montpellier, 34295, France

RECRUITING

Genetics department, Institut Jérôme Lejeune

Paris, 75725, France

RECRUITING

Service de Génétique, Chromosomique et Moléculaire, Chu de Saint Etienne

Saint-Etienne, 42270, France

RECRUITING

IRCCS Istituto Delle Scienze Neurologiche, Azienda Unita Sanitaria Locale Di Bologna

Bologna, 40139, Italy

RECRUITING

Centro di Medicina dell'Invecchiamento, Policlinico Universitario Agostino Gemelli IRCCS

Roma, 00168, Italy

RECRUITING

UOR of Neurofarmacology and Translational Neurosciences, Associazione Oasi Maria S.S.Onlus

Troina, 94018, Italy

RECRUITING

Integrative Pharmacology and Systems Neurosciences, Hospital del Mar Research Institute

Barcelona, 08003, Spain

RECRUITING

Servicio de Medicina Interna, Hospital Universitario De La Princesa

Madrid, 28006, Spain

NOT YET RECRUITING

MeSH Terms

Conditions

Down Syndrome; Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Officials

• Pier Vincenzo PIAZZA, MD, PhD

  Aelis Farma

  STUDY CHAIR

• Rafael DE LA TORRE FORNELL, PharmD, PhD

  Hospital del Mar Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stéphanie Monlezun, Ph. D

CONTACT

+33554542327; s.monlezun@aelisfarma.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Sponsor's team
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: * Participants will be randomized in a 1:1:1:1 ratio to 1 of 4 groups to receive 1 of 3 doses of AEF0217 ( 0.1, 0.2 or 0.6 mg) or placebo * Randomization will be stratified by baseline IQ score 1) mild disability (IQ \>55-70), 2) moderate disability (IQ \>35-55\] and by age group 3) older adolescent (≥16-\<18 years) 4) adults (≥18 to ≤32 years)

Study Record Dates

• First Submitted: November 20, 2025
• First Posted: January 12, 2026
• Study Start: December 22, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (3); FR (5); ES (2)