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Ion440

A groundbreaking clinical trial is underway to assess the potential of ION440, a new drug designed to treat MECP2 Duplication Syndrome (MDS). This study, known as ATTUNE, aims to evaluate the safety, tolerability, and effectiveness of ION440 when administered intrathecally (directly into the fluid surrounding the brain and spinal cord) in both children and adults with MDS. The trial consists of two parts: a 36-week multiple ascending dose study followed by a long-term extension phase lasting up to 156 weeks.

Table of Contents

What is ION440?

ION440 is an investigational drug currently being studied for the treatment of MECP2 Duplication Syndrome (MDS). This medication is being developed to address the underlying genetic cause of MDS, which is an overexpression of the MECP2 gene[1]. The drug is administered directly into the spinal fluid, a method known as intrathecal administration, to target the central nervous system where the effects of MDS are most prominent.

Target Condition: MECP2 Duplication Syndrome

MECP2 Duplication Syndrome is a rare genetic disorder caused by the presence of extra copies of the MECP2 gene. This condition primarily affects boys and is characterized by developmental delays, intellectual disability, seizures, and recurrent respiratory infections. By targeting the excess MECP2 gene products, ION440 aims to alleviate the symptoms and potentially improve the quality of life for individuals with MDS[1].

Clinical Trial Details

The clinical trial for ION440, named ATTUNE, is a Phase 1-2 study designed to evaluate the safety, tolerability, pharmacokinetics (how the drug moves through the body), and pharmacodynamics (how the drug affects the body) of the medication[1]. Here are the key details of the trial:

  • Study Design: The trial is randomized, double-blind, and sham-controlled. This means that participants are randomly assigned to either receive ION440 or undergo a sham procedure, and neither the participants nor the researchers know who is receiving the actual treatment until the study is complete.
  • Duration: The study is conducted in two parts:
    • Part 1 (Multiple Ascending Dose or MAD): Lasts approximately 36 weeks
    • Part 2 (Long-Term Extension or LTE): Lasts up to approximately 156 weeks
  • Participant Groups: The study includes both pediatric and adult participants with MDS, divided into two age groups:
    • Sub cohort A: Participants 8 years of age and older
    • Sub cohort B: Participants 2 through 7 years of age
  • Dosing: Multiple dose levels (Dose A, Dose B, and Dose C) will be evaluated in the study[1].

Administration Method

ION440 is administered through an intrathecal bolus (ITB) injection. This means the medication is injected directly into the fluid surrounding the spinal cord and brain, called the cerebrospinal fluid (CSF). This method allows the drug to bypass the blood-brain barrier and reach its target more effectively[1].

Study Objectives

The primary purpose of the ATTUNE study is to evaluate the safety and tolerability of ION440 in individuals with MECP2 Duplication Syndrome. Additionally, the study aims to assess how the drug moves through the body (pharmacokinetics) and how it affects the body (pharmacodynamics)[1].

Safety Monitoring

Throughout the study, participants will be closely monitored for any side effects or adverse reactions. The following aspects will be evaluated:

  1. Treatment-Emergent Adverse Events (TEAEs)
  2. Changes in vital signs
  3. Changes in physical and neurological examination findings
  4. Changes in laboratory assessments
  5. Changes in electrocardiogram (ECG) readings

These safety assessments will be conducted in both Part 1 and Part 2 of the study, ensuring continuous monitoring of the participants’ well-being[1].

Pharmacokinetics Assessment

To understand how ION440 moves through the body, researchers will measure several pharmacokinetic parameters, including:

  • Maximum Observed Concentration (Cmax): The highest concentration of ION440 observed in the plasma
  • Area Under the Concentration-time Curve (AUC): A measure of the total exposure to ION440 over time
  • Terminal Elimination Half-life (t½): The time it takes for half of the drug to be eliminated from the body
  • Trough Concentration (Ctrough): The lowest concentration of ION440 in plasma and CSF before the next dose

These measurements will help researchers determine the optimal dosing regimen for ION440 and understand how the drug behaves in the body over time[1].

Aspect Details
Study Name ATTUNE
Drug ION440
Condition MECP2 Duplication Syndrome (MDS)
Administration Method Intrathecal bolus (ITB) injection
Study Design Phase 1-2, randomized, double-blind, sham-controlled, multiple-ascending dose study
Study Duration Part 1: 36 weeks, Part 2: up to 156 weeks
Participant Age Groups 8 years and older, 2-7 years
Primary Outcomes Safety and tolerability assessments
Secondary Outcomes Pharmacokinetic measurements

FAQ

  • What is the main purpose of the ATTUNE clinical trial? The primary purpose of the ATTUNE clinical trial is to evaluate the safety and tolerability of ION440, a new drug designed to treat MECP2 Duplication Syndrome (MDS).
  • How is ION440 administered to patients in the trial? ION440 is administered intrathecally, which means it is injected directly into the fluid surrounding the brain and spinal cord through a procedure called an intrathecal bolus (ITB) injection.
  • Who can participate in the ATTUNE clinical trial? The trial includes both pediatric and adult participants with MECP2 Duplication Syndrome (MDS). Participants are divided into two age groups: those 8 years of age and older, and those between 2 and 7 years of age.
  • How long does the ATTUNE clinical trial last? The trial consists of two parts. Part 1 lasts approximately 36 weeks, and participants who complete this part may enter Part 2, which is a long-term extension study lasting up to about 156 weeks. In total, the trial can last up to approximately 192 weeks (about 3.7 years).
  • What are the main outcomes being measured in this trial? The main outcomes being measured include the number of participants experiencing treatment-emergent adverse events, changes in vital signs, physical and neurological examination findings, laboratory assessments, and electrocardiogram results. The trial also measures the concentration and behavior of ION440 in the body.

Ongoing Clinical Trials on Ion440

  • Study on the Safety and Effects of ION440 for Patients with MECP2 Duplication Syndrome

    Recruiting

    1 1
    Investigated diseases:
    Investigated drugs:
    Austria France Spain

Glossary

  • MECP2 Duplication Syndrome (MDS): A rare genetic disorder caused by the presence of extra copies of the MECP2 gene, leading to various developmental and neurological issues.
  • Intrathecal: Refers to the space under the arachnoid membrane of the brain or spinal cord. In this trial, it means the medication is injected directly into the fluid surrounding the brain and spinal cord.
  • Multiple Ascending Dose (MAD) study: A type of clinical trial where groups of participants receive increasing doses of a drug to evaluate its safety, tolerability, and effectiveness.
  • Pharmacokinetics: The study of how a drug moves through the body, including its absorption, distribution, metabolism, and excretion.
  • Pharmacodynamics: The study of how a drug affects the body, including its mechanism of action and relationship between drug concentration and effect.
  • Double-blind: A study design where neither the participants nor the researchers know who is receiving the actual treatment and who is receiving a placebo or sham treatment.
  • Sham-controlled: A type of clinical trial where some participants receive a fake treatment (sham) that mimics the real treatment but has no active ingredients.
  • Open-label: A type of clinical trial where both the researchers and participants know which treatment is being administered.
  • Treatment-Emergent Adverse Events (TEAEs): Any unfavorable and unintended sign, symptom, or disease that appears or worsens after starting a medical treatment.
  • Electrocardiogram (ECG): A test that measures the electrical activity of the heart to check for various heart conditions.
  • Cerebrospinal Fluid (CSF): The clear, colorless fluid that surrounds the brain and spinal cord, protecting them from injury and providing nutrients.

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