ION440: IONIS takes the MDS community to the next levelION440: IONIS takes the MDS community to the next level

Written by David and checked by Ionis

Following the recent announcement by Ionis about the upcoming clinical trial, we would like to provide further information about the trial. It is particularly important for families considering enrolling their child in a clinical trial to know what a clinical trial is, especially in the context of rare diseases such as MECP2 duplication syndrome (MDS).

A clinical trial (or therapeutic trial) is a type of research that studies new treatments and evaluates their safety and effects on humans. Clinical trials are often part of a wider clinical development programme. A clinical development programme is a series of clinical trials conducted in progressive phases (i.e. from phase 1 to phase 3) to determine whether potential new medicines or treatments are both sufficiently safe and significantly effective.

In the case of MDS, Ionis will soon launch a first clinical trial to evaluate a potential new treatment called ION440. The ATTUNE study was announced by Ionis on clinicaltrials.gov with its official title "A Phase 1-2, Double-Blind, Sham-Controlled Multiple Ascending Dose Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intrathecally-Administered ION440 in Patients With MECP2 Duplication Syndrome".

Let's decipher what this means.

Phase 1-2 test : Phase 1 represents the first time a drug is administered to humans (often referred to as a "first-in-human" trial). Phase 1 is primarily designed to determine the safety and tolerability of the investigational drug at different doses; it is generally small and relatively rapid. Phase 2 trials provide further evidence of safety by studying the impact of the new drug on a larger number of people over a longer period of time. Often, in phase 2 trials, including ATTUNE, researchers also seek to understand how people respond to different doses of the experimental drug. The ATTUNE trial is a combination of phase 1 and phase 2 trials.

Randomised, double-blind, Sham-controlled: This means that participants are randomly assigned to receive either the ION440 treatment or a sham treatment (no injection but the same sedation procedure as in the treatment group) in a 3:1 ratio (3 patients receiving ION440 to 1 patient receiving placebo). Neither the participants nor the researchers knew who was receiving the real treatment and who was receiving the sham.

A control group (here the 'sham' group) is often used when (1) the signs and symptoms of the disease are different from one person to another (2) the natural history of the trial population is limited (3) the objectives of the clinical trial can be defined in a way that could be considered subjective or subject to bias and (4) there is limited understanding of how the recruited population will respond to specific types of procedures, such as the sedation and lumbar puncture required to administer ION440, is limited.

Multiple ascending dose (MAD) : This means that researchers administer increasing doses of the drug to different groups of participants in order to determine how much of the drug can be administered safely.

Part 1 and part 2 of the test : ATTUNE is divided into two parts. All those accepted into the trial will start with part 1.
In part one, 75 % of participants will receive ION440 and 25 % will receive sham treatment for approximately 36 weeks. Once Ionis has successfully completed the safety assessment in the first part of the trial, participants who have completed the first part of the trial will have the opportunity to receive ION440 for 156 weeks in the extension phase (LTE), known as the second part.

Safety, tolerability, pharmacokinetics, pharmacodynamics : These criteria define the objectives of the phase 1-2 study for ION440 by assessing whether or what adverse effects may be observed after administration of ION440, what the body does to ION440, and what ION440 does to the human body.

Inclusion and exclusion criteria : These rules determine who can take part in the clinical trial. For example, in this trial, participants must be male, aged between 2 and 65, have a confirmed diagnosis of MECP2 gene duplication syndrome and be able to follow all the study procedures. Certain conditions may also prevent a person from taking part, such as having a complex form of the syndrome, suffering from certain health problems or being treated with other drugs.

It is important to note that participation in a clinical trial is voluntary and that families can withdraw at any time if they feel it is not in the best interests of their child.

Start of the study : The estimated start date for ATTUNE is August 2024. However, this timeline may change depending on regulatory milestones, such as ethics approval, contract signing, and other specific approvals required in each hospital where the study will be conducted. Patient enrolment will begin once all approvals have been signed by Ionis and the hospital.

Don't forget that clinical trials are essential for advancing medical knowledge and finding new treatments, and that they bring hope to individuals and families affected by rare diseases.

ION440 is an investigational medicinal product that has not been approved for marketing as a treatment for any disease, including MECP2 gene duplication syndrome, in any country.

We are currently preparing a detailed webinar on clinical trials and ATTUNE. It is scheduled for release by the end of September 2024. Stay tuned 😉