Written by David and verified by Ionis
Following Ionis’ recent announcement about the upcoming clinical trial, we aim to provide a clearer understanding of this trial. It is especially important for families considering enrolling their child to know what a clinical trial is, particularly in the context of rare diseases like MECP2 Duplication Syndrome (MDS).
A clinical trial is a research study that investigates new potential treatments, assessing their safety and effects on humans. Clinical trials are often conducted as part of a larger clinical development program. A clinical development program is a series of clinical trials conducted in progressive phases (i.e., Phase 1-3) designed to determine whether new potential drugs or treatments are both adequately safe and substantially effective.
In the case of MDS, Ionis will soon initiate a first clinical trial to evaluate a new potential treatment called ION440. This study, named ATTUNE, was recently 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 unpack what this means.
Phase 1-2 Trial: Phase 1 represents the first time that a drug is administered to humans (often referred to as a “first-in-human” trial). Phase 1 is mainly intended to determine the initial safety and tolerability of the investigational drug at different doses, they are usually small and relatively quick. Phase 2 trials provide additional evidence of safety by studying the impact of the investigational drug in more people over a longer period. Often in Phase 2 trials, including ATTUNE, investigators will also seek to understand how people react to different doses of the investigational drug. The ATTUNE trial is a combination of Phase 1 and Phase 2 trials together.
Randomized, Double-Blind, Sham-Controlled: This means that participants are randomly assigned to receive either the ION440 treatment or a sham treatment (no injection of ION440 but same sedation procedure as in treatment group) in a 3:1 ratio (3 patients receiving ION440 for 1 patient receiving no treatment). Neither the participants nor the researchers know who is receiving the real treatment and who is receiving the sham.
A control arm is often used when (1) the signs and symptoms of the disease are different from person to person (2) there is limited natural history in a the specific population being investigated in the trial (3) the objectives of the clinical trial may be captured in a way that could be considered subjective or subject to bias and (4) there is limited understanding for how the specific population of people enrolled will respond to specific types of procedures, like the sedation and lumbar puncture that are needed to deliver ION440.
Multiple-Ascending Dose (MAD): This means that the researchers are giving sequentially increasing doses of the investigational drug to different groups of participants to see how much of the drug can be given safely.
Part 1 and Part 2 of the Trial: ATTUNE is divided into two parts. All individuals accepted into the trial will begin in Part 1. In Part 1, 75% of participants will receive ION440 and 25% will receive a sham treatment for approximately 36 weeks. After Ionis successfully completes a safety review during the early part of the trial, participants who completed Part 1 will have an opportunity to receive ION440 for up to 156 weeks during the open-label extension (LTE), known as Part 2.
Safety, tolerability, pharmacokinetics, pharmacodynamics: These define the goals of the phase 1-2 study for ION440 by evaluating if or what side effects can be observed after the administration of ION440, what the body does to ION440, what ION440 does to the human body.
Inclusion and Exclusion Criteria: These are the rules that decide who can participate in the clinical trial. For example, in this trial, participants must be male, aged 2 to 65 years old, have a confirmed diagnosis of MDS, and be able to complete all study procedures. There are also certain conditions that would prevent someone from participating, such as having a complex form of MDS, having certain health conditions, or being treated with certain other drugs.
It’s important to note that participation in a clinical trial is voluntary, and families can withdraw at any time if they feel it is not in their child’s best interest.
Study start: The estimated start date for ATTUNE is August 2024. However, this timeline may change depending on regulatory steps such as ethics committee approval, contract signatures, and other site-specific approvals required at each hospital where the study will be conducted. Patient enrollment will begin once all approvals have been signed by both Ionis and the hospital.
Remember, clinical trials are essential for advancing medical knowledge and finding new treatments, and they offer hope for individuals and families affected by rare diseases.
ION440 is an investigational medicine and is not approved to be marketed as a treatment for any disorder, including MDS, in any country. Individuals with questions about changes in their health and healthcare overall should speak with their healthcare provider.
Stay tuned for our webinar on clinical trials and ATTUNE, expected to be released by the end of September 2024.
