The ATTUNE trial is a Phase 1/2 clinical study sponsored by Ionis. It aims to evaluate ION440, an investigational Antisense Oligonucleotide (ASO) therapy designed to address the root cause of MECP2 Duplication Syndrome (MDS).
Patient recruitment for the groundbreaking ATTUNE clinical trial has officially begun! The first site opened in November 2024 at Baylor College of Medicine in Houston, Texas (US), marking the start of this Phase 1/2 study. At the end of January 2025, a second site opened in Minnesota (US). Additional sites in the United States and globally are expected to open soon.
Trial Overview
The ATTUNE trial represents the first time ION440 has been administered to humans. The investigational ASO therapy aims to reduce the levels of MECP2 mRNA in individuals with MDS, addressing the root cause of symptoms caused by MECP2 overexpression.
This potential treatment approach has shown impressive results during preclinical research experiments. Studies conducted in 2021 in mouse models of MDS demonstrated that ASO therapy effectively reduced MECP2 levels, and reduced disease symptoms without significant adverse effects. Almost 10 years ago, these findings generated significant excitement and hope within the MDS community.
The trial enrolled male participants aged 2 to 65 years with a confirmed diagnosis of MECP2 Duplication Syndrome. The study will be divided into 2 parts. Part 1 (Multiple ascending doses) will last 36 weeks for each participant. During that phase, participants will be randomized to receive either ION440 or a sham procedure. Upon completion of part 1, a participant may move to part 2 (Long-term extension) and receive ION440 for up to 156 weeks.
Each participant will follow a detailed schedule, including an initial screening period, administration of ION440, and a follow-up phase to evaluate the safety, tolerability, and preliminary efficacy outcomes of the potential drug treatment. Participants will be enrolled sequentially in different cohorts, with each cohort receiving a different dose level of ION440.
For more details about the study protocol and overall study design, we invite you to explore the following resources:
- Our webinars explaining details about the ATTUNE study: Demystifying the ATTUNE Study
- Our article about the study protocol: ION440: IONIS brings MDS community to the next level
- Our e-book with all Q/A from families: Demystifying the ATTUNE Study
Next Steps & Goals
As a Phase 1/2 clinical trial, the primary goal of ATTUNE is to evaluate the safety and tolerability of ION440. The findings from the ATTUNE trial will provide valuable information for future studies to further evaluate the efficacy of ION440 as a treatment for MDS.
The research teams of the Children’s Hospital in Houston and Gillette Children’s Specialty Healthcare in Minnesota are currently recruiting patients to start the administration of the investigational therapy.
The launch of the ATTUNE clinical trial marks an extraordinary step forward in the search for a treatment for MECP2 Duplication Syndrome. As for the HERO clinical trial, the novel use of Antisense Oligonucleotide technology represents a cutting-edge approach to addressing this condition, offering renewed hope to families and the MDS community.
