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1-((3S,8S,9S,10R,13S,14S,17S)3-BENZYLOXY-10,13,17-TRIMETHYL-2,3,4,7,8,9,10,11,12,13,14,15,16,17-TETRADECAHYDRO-1HCYCLOPENTA[A]PHENANTHRENE-17-YL)ETHAN-1-ONE

This article discusses clinical trials investigating 1-((3S,8S,9S,10R,13S,14S,17S)3-BENZYLOXY-10,13,17-TRIMETHYL-2,3,4,7,8,9,10,11,12,13,14,15,16,17-TETRADECAHYDRO-1HCYCLOPENTA[A]PHENANTHRENE-17-YL)ETHAN-1-ONE, also known as AEF0217. The trials aim to evaluate the safety and efficacy of this substance in treating behavioral and cognitive impairments in individuals with Down syndrome, focusing on improvements in adaptive behaviors.

Table of Contents

Overview of Clinical Research

Clinical trials are currently investigating 1-((3S,8S,9S,10R,13S,14S,17S)3-BENZYLOXY-10,13,17-TRIMETHYL-2,3,4,7,8,9,10,11,12,13,14,15,16,17-TETRADECAHYDRO-1HCYCLOPENTA[A]PHENANTHRENE-17-YL)ETHAN-1-ONE, also known by its research designation AEF0217, as a potential treatment for individuals with Down syndrome[1]. Down syndrome is a genetic condition that affects cognitive development and often leads to behavioral challenges and difficulties with adaptive functioning. These adaptive behaviors include essential everyday skills such as communication, social interaction, self-care, and practical activities needed for independent living.

The research focuses specifically on whether 1-((3S,8S,9S,10R,13S,14S,17S)3-BENZYLOXY-10,13,17-TRIMETHYL-2,3,4,7,8,9,10,11,12,13,14,15,16,17-TETRADECAHYDRO-1HCYCLOPENTA[A]PHENANTHRENE-17-YL)ETHAN-1-ONE can improve behavioral and cognitive impairments that affect quality of life for people with Down syndrome[1]. Understanding how this substance affects adaptive behaviors is crucial because improvements in these areas can significantly enhance independence, social participation, and overall functioning in daily life.

Trial Design and Methodology

The clinical trial investigating 1-((3S,8S,9S,10R,13S,14S,17S)3-BENZYLOXY-10,13,17-TRIMETHYL-2,3,4,7,8,9,10,11,12,13,14,15,16,17-TETRADECAHYDRO-1HCYCLOPENTA[A]PHENANTHRENE-17-YL)ETHAN-1-ONE is a Phase 2B interventional study, which means it is designed to test whether the treatment is effective and to determine the optimal dose for therapeutic benefit[1]. This phase of research involves a larger number of participants than earlier Phase 1 studies and provides more detailed information about how well the treatment works.

The trial has received authorization to proceed and plans to enroll 188 participants with Down syndrome[1]. This sample size is carefully calculated to provide sufficient statistical power to detect meaningful differences between treatment groups while ensuring participant safety. The study design includes a placebo control group, which allows researchers to compare the effects of active treatment against an inactive substance that looks identical but contains no therapeutic ingredient.

The treatment period lasts for 24 weeks, during which participants receive either 1-((3S,8S,9S,10R,13S,14S,17S)3-BENZYLOXY-10,13,17-TRIMETHYL-2,3,4,7,8,9,10,11,12,13,14,15,16,17-TETRADECAHYDRO-1HCYCLOPENTA[A]PHENANTHRENE-17-YL)ETHAN-1-ONE at one of two dose levels or placebo[1]. This duration is chosen to allow sufficient time for behavioral changes to emerge and be measured reliably, while also providing safety data over an extended treatment period.

Target Population and Eligibility

The clinical trial is specifically designed for individuals diagnosed with Down syndrome who experience behavioral and cognitive impairments[1]. Down syndrome, also known as trisomy 21, is a genetic condition caused by an extra copy of chromosome 21. This chromosomal difference affects brain development and function, leading to varying degrees of intellectual disability and challenges with learning, memory, and behavior.

The research recognizes that Down syndrome affects individuals differently, with varying levels of impairment. The trial design specifically examines participants across different categories to understand how 1-((3S,8S,9S,10R,13S,14S,17S)3-BENZYLOXY-10,13,17-TRIMETHYL-2,3,4,7,8,9,10,11,12,13,14,15,16,17-TETRADECAHYDRO-1HCYCLOPENTA[A]PHENANTHRENE-17-YL)ETHAN-1-ONE works in diverse populations[1]. The study includes participants with both mild and moderate degrees of disability, recognizing that treatment effects may differ depending on the severity of cognitive impairment.

Age is another important consideration in the trial design. The researchers are investigating how different age groups respond to treatment, as the manifestation of behavioral and cognitive symptoms in Down syndrome can change across the lifespan[1]. Understanding age-related differences in treatment response is essential for determining which populations may benefit most from this therapeutic approach.

Treatment Interventions and Dosing

The trial tests 1-((3S,8S,9S,10R,13S,14S,17S)3-BENZYLOXY-10,13,17-TRIMETHYL-2,3,4,7,8,9,10,11,12,13,14,15,16,17-TETRADECAHYDRO-1HCYCLOPENTA[A]PHENANTHRENE-17-YL)ETHAN-1-ONE at two different dose levels to determine which provides the best balance of effectiveness and safety[1]. The study includes three treatment arms:

  • Low dose group: Participants receive 0.2 mg of 1-((3S,8S,9S,10R,13S,14S,17S)3-BENZYLOXY-10,13,17-TRIMETHYL-2,3,4,7,8,9,10,11,12,13,14,15,16,17-TETRADECAHYDRO-1HCYCLOPENTA[A]PHENANTHRENE-17-YL)ETHAN-1-ONE administered orally[1]
  • High dose group: Participants receive 0.6 mg of 1-((3S,8S,9S,10R,13S,14S,17S)3-BENZYLOXY-10,13,17-TRIMETHYL-2,3,4,7,8,9,10,11,12,13,14,15,16,17-TETRADECAHYDRO-1HCYCLOPENTA[A]PHENANTHRENE-17-YL)ETHAN-1-ONE administered orally[1]
  • Placebo group: Participants receive an inactive substance that looks identical to the active treatment but contains no therapeutic ingredient[1]

The medication is administered via the oral route, meaning participants take it by mouth[1]. This method of administration is convenient and non-invasive, making it practical for long-term use if the treatment proves effective. The choice of these specific doses is based on earlier research phases that established preliminary safety and suggested potential therapeutic effects at these levels.

By testing two different doses against placebo, researchers can determine whether there is a dose-response relationship, meaning whether higher doses produce greater therapeutic effects. This information is crucial for identifying the optimal dose that maximizes benefits while minimizing potential risks or side effects.

Primary Outcomes and Measurements

The primary outcome measure for the trial is the change in adaptive behaviors as assessed by the Vineland Adaptive Behavior Scales, Third Edition (VABS-3)[1]. The VABS-3 is a comprehensive, standardized assessment tool widely used to evaluate adaptive functioning in individuals with developmental disabilities. It provides detailed information about a person’s ability to perform everyday activities needed for independent living.

The VABS-3 evaluates adaptive behaviors across nine subdomains, which cover different aspects of daily functioning[1]. These subdomains typically include areas such as receptive and expressive communication, written communication, personal daily living skills, domestic daily living skills, community daily living skills, interpersonal relationships, play and leisure time, and coping skills. By measuring all nine subdomains, researchers can obtain a comprehensive picture of how treatment affects different aspects of adaptive functioning.

The trial measures the change from baseline to the end of Week 24, which corresponds to the completion of the treatment period[1]. Baseline measurements are taken before treatment begins, establishing a starting point for each participant. At the end of 24 weeks, the same assessments are repeated, and researchers calculate the change in scores. This approach allows for precise measurement of treatment effects while accounting for individual differences in starting abilities.

The study uses normalized raw scores for analysis, which means the actual test scores are adjusted using statistical methods to allow fair comparisons between different individuals and time points[1]. This normalization process is important because it accounts for factors such as age-expected development and ensures that observed changes truly reflect treatment effects rather than natural developmental progression or measurement variability.

Factors Influencing Treatment Response

The clinical trial is designed to investigate several factors that may influence how individuals respond to 1-((3S,8S,9S,10R,13S,14S,17S)3-BENZYLOXY-10,13,17-TRIMETHYL-2,3,4,7,8,9,10,11,12,13,14,15,16,17-TETRADECAHYDRO-1HCYCLOPENTA[A]PHENANTHRENE-17-YL)ETHAN-1-ONE[1]. Understanding these factors is essential for identifying which patients are most likely to benefit from treatment and for personalizing therapeutic approaches in the future.

One important factor under investigation is age group. The trial examines whether younger and older participants respond differently to treatment[1]. Age-related differences in brain development, neuroplasticity, and symptom presentation may all affect how well the treatment works. Identifying optimal age ranges for intervention could help guide clinical decision-making and treatment timing.

The degree of disability is another key factor being studied. The trial specifically compares treatment effects in participants with moderate versus mild intellectual disability[1]. Understanding whether the treatment works equally well across different severity levels is crucial for determining which patients should be prioritized for this therapeutic approach and whether dose adjustments might be needed based on disability severity.

The trial also investigates the role of APOE4 genotype in treatment response[1]. The APOE gene provides instructions for making a protein involved in fat metabolism in the body, and different variants of this gene have been associated with various neurological conditions. The APOE4 variant has been particularly studied in relation to cognitive function and neurodegenerative diseases. By examining whether individuals with different APOE genotypes respond differently to 1-((3S,8S,9S,10R,13S,14S,17S)3-BENZYLOXY-10,13,17-TRIMETHYL-2,3,4,7,8,9,10,11,12,13,14,15,16,17-TETRADECAHYDRO-1HCYCLOPENTA[A]PHENANTHRENE-17-YL)ETHAN-1-ONE, researchers can better understand the biological mechanisms underlying treatment effects and potentially identify genetic markers that predict treatment success.

Additionally, the study measures plasma concentrations of specific biochemical markers at baseline, including AEA (anandamide) and 2-AG (2-arachidonoylglycerol)[1]. These are endogenous compounds that play roles in various physiological processes. The trial investigates whether baseline levels of these substances influence how well patients respond to treatment. This information could potentially be used to identify biomarkers that predict treatment response, allowing for more personalized treatment selection in the future.

The research also aims to understand the dynamics of treatment effects over time[1]. Rather than simply measuring outcomes at the end of treatment, the study examines how quickly improvements emerge, whether effects continue to increase throughout the treatment period, and whether certain domains of adaptive behavior respond more rapidly than others. This temporal information is valuable for setting realistic expectations for patients and families and for optimizing treatment duration in future clinical practice.

Trial ID Phase Condition Studied Status Enrollment Doses Tested Treatment Duration
2025-521013-10-00 Phase 2 Behavioral and cognitive impairments in Down syndrome Authorised 188 participants 0.2 mg and 0.6 mg oral (vs placebo) 24 weeks

FAQ

  • What is 1-((3S,8S,9S,10R,13S,14S,17S)3-BENZYLOXY-10,13,17-TRIMETHYL-2,3,4,7,8,9,10,11,12,13,14,15,16,17-TETRADECAHYDRO-1HCYCLOPENTA[A]PHENANTHRENE-17-YL)ETHAN-1-ONE being studied for? Clinical trials are investigating 1-((3S,8S,9S,10R,13S,14S,17S)3-BENZYLOXY-10,13,17-TRIMETHYL-2,3,4,7,8,9,10,11,12,13,14,15,16,17-TETRADECAHYDRO-1HCYCLOPENTA[A]PHENANTHRENE-17-YL)ETHAN-1-ONE (AEF0217) for the treatment of behavioral and cognitive impairments in people with Down syndrome. The research focuses on whether this substance can improve adaptive behaviors, which are everyday skills needed for independent living.
  • Who can participate in these clinical trials? The trials are designed for participants with Down syndrome who experience behavioral and cognitive impairments. The research examines different age groups and levels of disability, including both mild and moderate impairment, to understand how the treatment works across diverse populations.
  • What phase are the trials in? The clinical trial investigating 1-((3S,8S,9S,10R,13S,14S,17S)3-BENZYLOXY-10,13,17-TRIMETHYL-2,3,4,7,8,9,10,11,12,13,14,15,16,17-TETRADECAHYDRO-1HCYCLOPENTA[A]PHENANTHRENE-17-YL)ETHAN-1-ONE is in Phase 2. This phase focuses on determining the optimal dose and evaluating whether the treatment is effective in improving adaptive behaviors in people with Down syndrome.
  • How long does the treatment last in the trial? In the clinical trial, participants receive 1-((3S,8S,9S,10R,13S,14S,17S)3-BENZYLOXY-10,13,17-TRIMETHYL-2,3,4,7,8,9,10,11,12,13,14,15,16,17-TETRADECAHYDRO-1HCYCLOPENTA[A]PHENANTHRENE-17-YL)ETHAN-1-ONE for 24 weeks. Researchers measure changes in adaptive behaviors from the beginning of treatment to the end of this 24-week period.
  • What doses are being tested in the trials? The clinical trial is testing two different doses of 1-((3S,8S,9S,10R,13S,14S,17S)3-BENZYLOXY-10,13,17-TRIMETHYL-2,3,4,7,8,9,10,11,12,13,14,15,16,17-TETRADECAHYDRO-1HCYCLOPENTA[A]PHENANTHRENE-17-YL)ETHAN-1-ONE: 0.2 mg and 0.6 mg, both given orally. These doses are compared against placebo to determine which dose provides the best improvement in behavioral and cognitive outcomes.

Ongoing Clinical Trials on 1-((3S,8S,9S,10R,13S,14S,17S)3-BENZYLOXY-10,13,17-TRIMETHYL-2,3,4,7,8,9,10,11,12,13,14,15,16,17-TETRADECAHYDRO-1HCYCLOPENTA[A]PHENANTHRENE-17-YL)ETHAN-1-ONE

  • Study of AEF0217 compared to placebo for improving behavior and thinking skills in adults and older adolescents with Down syndrome

    Recruiting

    1
    Investigated drugs:
    France Italy Spain

Glossary

  • Adaptive Behaviors: Everyday skills needed for independent living, such as communication, social interaction, self-care, and practical daily activities. These behaviors are important for functioning in home, school, and community settings.
  • Phase 2 Trial: A type of clinical study that tests whether a treatment works and determines the best dose to use. Phase 2 trials involve more participants than Phase 1 and focus on effectiveness and safety.
  • Placebo: An inactive substance that looks like the real treatment but contains no active drug. Placebos are used in clinical trials to compare the effects of the actual treatment against no treatment.
  • VABS-3: Vineland Adaptive Behavior Scales, Third Edition. A standardized assessment tool that measures adaptive behaviors across different areas of daily functioning, including communication, daily living skills, and socialization.
  • Normalized Raw Scores: Test scores that have been adjusted using statistical methods to allow fair comparison between different people or time points. This helps researchers accurately measure changes in behavior or abilities.
  • APOE4 Genotype: A specific genetic variation in the APOE gene. Different APOE genotypes may influence how people respond to treatments, particularly those affecting brain function and cognition.
  • Baseline: The starting point measurements taken before treatment begins. Baseline data are used as a reference to measure how much change occurs during and after treatment.
  • Cognitive Impairments: Difficulties with mental processes such as thinking, learning, memory, attention, and problem-solving. These challenges can affect daily functioning and quality of life.
  • Interventional Study: A type of clinical trial where researchers give participants a specific treatment or intervention and measure its effects. This differs from observational studies where researchers only watch what happens naturally.
  • Primary Outcome: The main result that researchers measure to determine whether a treatment works. In clinical trials, the primary outcome is the most important question the study aims to answer.
  • Oral Administration: Taking medication by mouth, usually in the form of tablets, capsules, or liquid. This is one of the most common and convenient ways to take medicine.
  • Plasma Concentrations: The amount of a substance measured in the liquid part of blood. Researchers measure plasma concentrations to understand how the body processes substances and how they might affect treatment response.

References

  1. https://clinicaltrials.gov/study/2025-521013-10-00