Phase 1/2 Trial of AEF0217 in Participants With Down Syndrome

NCT05748405 | Completed Phase 1 DMC

• 2 other identifiers: AEF0217-1022022-000923-19
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 3

Brief Summary

AEF0217-102 clinical trial assesses the safety, tolerability, plasma exposure and preliminary indications of pharmacodynamic activity of AEF0217 in female and male adult participants with Down syndrome between 18 and 35 years old. The trial AEF0217-102 is a double-blind, randomized, placebo-controlled, multiple-dose, 4-week phase 1/2 study. After a screening period, the participant will be randomised and will take an oral dose of AEF0217 0.2mg or placebo once a day for 28 days.

Conditions

Down Syndrome

Keywords

Down Syndrome; Trisomy 21

Outcome Measures

Primary Outcomes (4)

• Incidence of TEAEs and TESAEs as assessed by ElectroCardioGram (ECG)

  By evaluating changes from the baseline in ECG parameters

  Day1, Day 8, Day14, Day21, Day29, Day56

• Incidence of TEAEs and TESAEs as assessed by vital signs

  By evaluating changes from the baseline in vital signs

  Day1, Day4, Day 8, Day14, Day21, Day27, Day 28, Day29, Day42, Day56

• Incidence of TEAEs and TESAEs as assessed by Laboratory clinical parameters

  By evaluating changes from the baseline in clinical laboratory values from blood and urine samples.

  Day1, Day 8, Day14, Day21, Day29, Day56

• Incidence of TEAEs or TESAEs

  Assessed by AE and SAE reporting

  From Day1 to Day56

Secondary Outcomes (7)

• Potential effects of AEF0217 on cognition using the NIH-ToolBox for ID corrected fluid cognitive

  Day1, Day27

• Determination of the minimum plasma concentration of AEF0217 before dosing (cthrough)

  Day1, Day4, Day8, Day14, Day21, Day22, Day29, Day42, Day56

• Determination of the peak plasma concentration of AEF0217 (Cmax)

  Day1, Day4, Day8, Day14, Day21, Day22, Day29, Day42, Day56

• Determination of the Time of peak concentration of AEF0217 (Tmax)

  Day1, Day4, Day8, Day14, Day21, Day22, Day29, Day42, Day56

• Determination of the plasma half-life of AEF0217 (t1/2)

  Day1, Day4, Day8, Day14, Day21, Day22, Day29, Day42, Day56

Other Outcomes (2)

• Responses to treatment according to APOE genotypes.

  Day 56

• To explore effects on additional ElectroEncephaloGram parameters

  Day28

Study Arms (2)

AEF0217

EXPERIMENTAL

AEF0217 0.1 mg tablet 2 tablets in 10 ml of water per day during 28 days

Drug: AEF0217

Placebo

PLACEBO COMPARATOR

Placebo tablet 2 tablets in 10 ml of water per day during 28 days

Drug: Placebo

Interventions

Placebo DRUG

Matching Tablets

Placebo

AEF0217 DRUG

Tablets of 100 mcg AEF0217

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

AEF0217

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female.
• Age ≥18 to ≤35 years.
• Body mass index (BMI) ≥18.5 to ≤32 kg/m2.
• Clinical diagnosis of Down syndrome (full trisomy 21 and translocations) documented by chromosomal analysis (karyotyping).
• Understands and accepts the trial procedures.
• Independently mobile and have sufficient vision and hearing to participate in the trial evaluations.
• Clinical Evaluation of Language Fundamentals Preschool-2 (CELF Preschool-2) test score ≥7.
• IQ \>35-70 measured with KBIT. Individuals with IQ from \>35 to \<40 must have adequate adaptive functioning according to the judgment of the principal investigator.
• Must have a parent or other reliable caregiver who agrees to accompany the participant to all clinic visits and be available for a telephone visit, provide information about the participant as required by the protocol, and ensure compliance with the medication schedule and protocol requirements.
• Vital signs, electrocardiogram (ECG), and safety laboratory parameters must be within normal ranges or without clinically relevant abnormalities except for:
• Stable type 1 or type 2 diabetes, i.e., HbA1c level \<7%, provided participants are monitored regularly prior to and during the trial to ensure adequate glucose control.
• Hypothyroidism provided participants are euthyroid and stable on treatment for at least 6 weeks prior to screening.
• Assent by the participant and consent by the legally authorized representative(s) on behalf of the participant or Consent by the participant in situations where consent rather than assent can be provided by the participant.
• Informed consent by the participant's caregiver to take on the obligations of the caregiver in this trial.

You may not qualify if:

• Pregnant or nursing female.
• Mosaic Down syndrome.
• Active or clinically relevant conditions that could, in the investigator's judgment, affect absorption, distribution, or metabolism of the trial intervention (e.g., inflammatory bowel disease, gastric or duodenal ulcers).
• Clinically relevant obstructive pulmonary disease or asthma that is untreated or not controlled by treatment within 6 weeks of screening or being treated with oral steroids.
• Severe obstructive sleep apnea.
• Recent (≤1 year) or ongoing hematologic or oncologic disorders (mild anemia is allowed).
• Personal history of infantile spasms/convulsions/epilepsy, severe head trauma, or CNS infections (e.g., meningitis), except for isolated events of febrile seizures more than 8 years ago.
• Clinically relevant unstable gastrointestinal, renal, hepatic, endocrine, or cardiovascular system disease.
• Current Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnosis including autism spectrum disorder or any primary psychiatric diagnosis. Diagnoses that are secondary, such as attention deficit hyperactivity disorder, depression, and conduct disorder are allowed if they are considered not to interfere with the trial conduct and are stable during the 3 months preceding randomization. Medical or behavioral treatments used for stabilization must be on stable regimen and dosing for the last 3 months and the type of treatment must be allowed according to the list of allowed and prohibited medication .
• Treatment with medication known to induce CYP3A4/5 P450 isozymes.
• Intake of vitamin supplements, catechins, or products containing epigallocatechin gallate (EGCG) (e.g., TEAVIGO, Mega Green Tea Capsules Life Extension, or Font-UP Grand Fontaine Laboratories) currently or during the 2 months prior to the baseline assessement.
• Symptoms of early dementia as assessed by the National Task Group-Early Detection Screen for Dementia (NTG-EDSD).
• Disclosure of drug or alcohol abuse during medical interview/anamnesis at screening and/or positive urine test for alcohol or drugs of abuse at screening or/and baseline.
• Epileptiform abnormalities (excluding isolated sharp waves and beyond those expected for age) in the screening EEG performed over 10 minutes with concurrent video recording and evaluated by an expert.
• Participants with a history of suicide attempt or deliberate self-harm due to suicidal ideation. Suicidal ideation (even in the absence of suicide attempt or deliberate self-harm) during the 12 months prior to screening. Assessed by 3 specific questions on suicidal ideation, suicidal behavior, and any self-injurious behavior.

Sponsors & Collaborators

• Aelis Farma: lead
• European Commission: collaborator

Study Sites (3)

Hospital del Mar Medical Research Institute (IMIM),

Barcelona, Catalonia, 08003, Spain

Location

Sant Pau Memory Clinic, Hospital de la Santa Creu i Sant Pau

Barcelona, 08025, Spain

Location

Unidad de Adultos con Síndrome de Down, Hospital de La Princesa

Madrid, 28006, Spain

Location

Related Links

• The ICOD project, funded by European Union (EU) aims to develop the first pharmacological therapy for cognitive impairment in Down syndrome (DS) making it accessible to patients worldwide.

MeSH Terms

Conditions

Down Syndrome

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

Study Officials

• Rafael De la Torre Fornell

  IMIM

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2023
• First Posted: February 28, 2023
• Study Start: December 15, 2022
• Primary Completion: October 7, 2024
• Study Completion: October 7, 2024
• Last Updated: October 10, 2024

Record last verified: 2024-10

Locations

ES (3)