Down SyndromePhase 1/2MDDSNCT05748405
Phase 1/2 Trial of AEF0217 in Participants With Down Syndrome
A Phase 1/2 study testing AEF0217 in people with Down Syndrome, run by Aelis Farma at 3 sites in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 35 years
- Conditions the study is for
- Down Syndrome
- What is being tested?
- AEF0217
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 3 sitesSpain
- Study dates
- 15 Dec 2022to 7 Oct 2024
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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).
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- 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.
- Known hypersensitivity to any drug.
- Participants with clinically significant illness from 2 weeks prior to screening until Day -1.
- Covid-19 positive test and/or symptoms within the last 10 days prior to Day -1, or according to the requirements of the hospital.
- History of or current life-threatening disease.
- Any other clinically relevant concomitant disease or condition or finding at screening that in the investigator's judgment could jeopardize the participant's safety or interfere with, or the treatment thereof might interfere with, the conduct of the trial and related procedures and/or might bias interpretation of the trial results.
Trial locations and contacts
3 sites in 1 country.
Spain3 sites
Hospital del Mar Medical Research Institute (IMIM),
Barcelona, Catalonia, 08003
Sant Pau Memory Clinic, Hospital de la Santa Creu i Sant Pau
Barcelona, 08025
Unidad de Adultos con Síndrome de Down, Hospital de La Princesa
Madrid, 28006
About this study
Official title: A Double-blind, Randomized, Placebo-controlled, 4-week, Phase 1/2 Trial in Young Adult Participants With Down Syndrome to Assess the Safety, Tolerability, Plasma Exposure, and Preliminary Indications of Pharmacodynamic Activity of AEF0217
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
- Being tested
- Placebo, AEF0217
- Keywords
- Down Syndrome, Trisomy 21
- Medical subject headings
- Down Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Matching Tablets
AEF0217Drug
Also called 3β-benzyloxy-17α-methyl-pregn-5-en-20-one
Tablets of 100 mcg AEF0217
| Study group | Role | What they receive |
|---|---|---|
| AEF0217 | Experimental | AEF0217 0.1 mg tablet 2 tablets in 10 ml of water per day during 28 days Receives: Drug: AEF0217 |
| Placebo | Placebo comparator | Placebo tablet 2 tablets in 10 ml of water per day during 28 days Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of TEAEs and TESAEs as assessed by ElectroCardioGram (ECG)
By evaluating changes from the baseline in ECG parameters
Measured: 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
Measured: 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.
Measured: Day1, Day 8, Day14, Day21, Day29, Day56
Incidence of TEAEs or TESAEs
Assessed by AE and SAE reporting
Measured: From Day1 to Day56
Secondary outcomes (7)
Potential effects of AEF0217 on cognition using the NIH-ToolBox for ID corrected fluid cognitive
Change from baseline in the corrected fluid cognition composite t-score of the NIH-ToolBox for ID Change from baseline in the scores of each of the individual 5 tests constituting the fluid cognition composite score
Measured: Day1, Day27
Determination of the minimum plasma concentration of AEF0217 before dosing (cthrough)
AEF0217 concentration will be determined. Ctrough (at steady state) will be estimated based on the plasma concentration-time profile of AEF0217.
Measured: Day1, Day4, Day8, Day14, Day21, Day22, Day29, Day42, Day56
Determination of the peak plasma concentration of AEF0217 (Cmax)
AEF0217 concentration will be determined based on the plasma concentration-time profile of AEF0217 and AEF0217 PK parameter Cmax will be estimated.
Measured: Day1, Day4, Day8, Day14, Day21, Day22, Day29, Day42, Day56
Determination of the Time of peak concentration of AEF0217 (Tmax)
AEF0217 concentration will be determined and AEF0217 PK parameter Tmax will be estimated.
Measured: Day1, Day4, Day8, Day14, Day21, Day22, Day29, Day42, Day56
Determination of the plasma half-life of AEF0217 (t1/2)
AEF0217 concentration will be determined and AEF0217 PK parameter t1/2 will be estimated.
Measured: Day1, Day4, Day8, Day14, Day21, Day22, Day29, Day42, Day56
Determination of the Area under the plasma concentration versus time curve of AEF0217 (AUC)
AEF0217 concentration will be determined, based on the plasma concentration-time profile of AEF0217 and AEF0217 PK parameter AUC will be estimated.
Measured: Day1, Day4, Day8, Day14, Day21, Day22, Day29, Day42, Day56
Effect on ElectroEncephaloGram (EEG) parameters
Difference between active and placebo at Day 28 in the following EEG parameters:
- Gamma intertrial coherence (ITC) during an ASSR at 40 Hz.
- Interhemispheric connectivity (IHC) in resting state (eyes open/closed): Band coherence, phase lag index (PLI).
- Event-related potential (ERP) associated to novel stimuli in the parietal midline (Pz) during the 3-stimuli oddball task.
- Cognitive workload and working memory EEG features during the working memory test of CANTAB (Spatial Span Test)
Measured: Day28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2023
- Study start15 Dec 2022
- Primary completion7 Oct 2024
- Study completion7 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Down SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aelis Farma
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- European Commission
- Responsible party
- Sponsor
- Investigators
- Rafael De la Torre Fornell, Principal investigator, IMIM
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05748405
- Sponsor's protocol ID
- AEF0217-102
- Other IDs
- 2022-000923-19
- Acronym
- MDDS
- Status last verified
- Oct 2024
- First submitted
- 11 Jan 2023
- Last updated
- 10 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-blind, Randomized, Placebo-controlled, 4-week, Phase 1/2 Trial in Young Adult Participants With Down Syndrome to Assess the Safety, Tolerability, Plasma Exposure, and Preliminary Indications of Pharmacodynamic Activity of AEF0217
- ClinicalTrials.gov ID
- NCT05748405
- Acronym / sponsor ID
- MDDS / AEF0217-102
- Conditions
- Down Syndrome
- Keywords
- Down Syndrome, Trisomy 21
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Aelis FarmaIndustry (pharma, biotech, devices)
- Collaborators
- European Commission
- Study start
- 15 Dec 2022 (actual)
- Primary completion
- 7 Oct 2024 (actual)
- Study completion
- 7 Oct 2024 (actual)
- First posted
- 28 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AEF0217 | Experimental | Drug: AEF0217AEF0217 0.1 mg tablet 2 tablets in 10 ml of water per day during 28 days |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo tablet 2 tablets in 10 ml of water per day during 28 days |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (14 listed)
- 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.
Key exclusion criteria (20 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboMatching Tablets | Drug | Placebo |
| AEF0217Also: 3β-benzyloxy-17α-methyl-pregn-5-en-20-oneTablets of 100 mcg AEF0217 | Drug | AEF0217 |
Primary outcome
Incidence of TEAEs and TESAEs as assessed by ElectroCardioGram (ECG)
Time frame: Day1, Day 8, Day14, Day21, Day29, Day56
By evaluating changes from the baseline in ECG parameters
Incidence of TEAEs and TESAEs as assessed by vital signs
Time frame: Day1, Day4, Day 8, Day14, Day21, Day27, Day 28, Day29, Day42, Day56
By evaluating changes from the baseline in vital signs
Incidence of TEAEs and TESAEs as assessed by Laboratory clinical parameters
Time frame: Day1, Day 8, Day14, Day21, Day29, Day56
By evaluating changes from the baseline in clinical laboratory values from blood and urine samples.
Incidence of TEAEs or TESAEs
Time frame: From Day1 to Day56
Assessed by AE and SAE reporting
7 secondary outcomes
Potential effects of AEF0217 on cognition using the NIH-ToolBox for ID corrected fluid cognitive
Time frame: Day1, Day27
Determination of the minimum plasma concentration of AEF0217 before dosing (cthrough)
Time frame: Day1, Day4, Day8, Day14, Day21, Day22, Day29, Day42, Day56
Determination of the peak plasma concentration of AEF0217 (Cmax)
Time frame: Day1, Day4, Day8, Day14, Day21, Day22, Day29, Day42, Day56
Determination of the Time of peak concentration of AEF0217 (Tmax)
Time frame: Day1, Day4, Day8, Day14, Day21, Day22, Day29, Day42, Day56
Determination of the plasma half-life of AEF0217 (t1/2)
Time frame: Day1, Day4, Day8, Day14, Day21, Day22, Day29, Day42, Day56
Determination of the Area under the plasma concentration versus time curve of AEF0217 (AUC)
Time frame: Day1, Day4, Day8, Day14, Day21, Day22, Day29, Day42, Day56
Effect on ElectroEncephaloGram (EEG) parameters
Time frame: Day28
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Oct 2024.
- 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.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rafael De la Torre Fornell principal investigator
IMIM
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing AEF0217 in people with Down Syndrome, run by Aelis Farma at 3 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of TEAEs and TESAEs as assessed by ElectroCardioGram (ECG) (time frame: Day1, Day 8, Day14, Day21, Day29, Day56). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Oct 2024.