Actively Recruiting
A Phase 1-2 Study to Evaluate Safety, Tolerability, and Pharmacology of Intrathecal ION440 in Males With MECP2 Duplication Syndrome
Led by Ionis Pharmaceuticals, Inc. · Updated on 2026-03-24
48
Participants Needed
11
Research Sites
134 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of the drug ION440 in people with Methyl CpG Binding Protein 2 (MECP2) Duplication Syndrome (MDS). This phase 1-2 randomized, double-blind, sham-controlled study includes both pediatric and adult participants to better understand how ION440 affects this rare genetic condition. The study is sponsored by Ionis Pharmaceuticals, Inc. and aims to carefully monitor treatment impacts over time. Participants will be randomly assigned to receive one of three different doses of ION440 or a sham procedure during the first part of the study, which lasts about 36 weeks. ION440 is given by injection into the spinal fluid (intrathecal bolus). After completing the first part, participants may enter a second open-label extension lasting up to approximately 156 weeks, where they receive the same dose of ION440 as before. The study includes two age groups: children aged 2 to 7 years and participants aged 8 to 65 years. The dosing groups are evaluated sequentially, starting with the older group. During the study, participants will undergo physical and neurological exams, vital sign checks, lab tests, electrocardiograms, and monitoring for any adverse effects. Blood and cerebrospinal fluid samples will be collected to measure drug levels. The study will assess the number of participants experiencing treatment-related side effects and changes in health markers over both the initial 36-week period and the longer extension. Participants are expected to complete all study visits and procedures to support these evaluations, which together may last more than three years.
CONDITIONS
Brief Title
ATTUNE: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intrathecally-Administered ION440 in Participants With Methyl CpG Binding Protein 2 (MECP2) Duplication Syndrome (MDS)
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Males aged 2 to 65 years, assigned to specific age groups for dosing
- Have a genetic confirmation of MECP2 Duplication Syndrome diagnosis
- Have a parent or caregiver aged 18 or older able to provide informed consent and assist with study activities
- Currently receiving stable doses of medications for at least 1 month before screening
- Able to complete all study procedures and visits as judged by the Investigator
You will not qualify if you...
- Diagnosis of severe MECP2 duplications or severe variant structure with specific clinical features like early seizures or oxygen dependence
- Significant abnormal vital signs or ECG at screening
- Any brain or spinal disease that would interfere with lumbar puncture or cerebrospinal fluid circulation
- Any condition deemed unsuitable by the Investigator that could interfere with study conduct or pose risk
- Treatment with investigational drugs or devices within 30 days or 5 half-lives of screening
- Previous treatment with oligonucleotides within specified washout periods
- Current participation in another investigational trial or recent use of investigational agents
- History of gene therapy, cell transplantation, or experimental brain surgery
- Active infection requiring ongoing antiviral or antimicrobial treatment
- Status Epilepticus within the past 6 months
- Development of new significant diseases or conditions during the study that affect suitability for continued treatment
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Up to approximately 36 weeks
Participants receive intrathecal doses of ION440 or undergo a sham procedure during the multiple-ascending dose (MAD) period.
Repeated visits for dosing and assessments over 36 weeks
Duration - Up to approximately 156 weeks
Participants who complete Part 1 may enter an open-label long-term extension where they receive ION440 at their assigned dose.
Visits scheduled for dosing and monitoring during long-term extension
Trial Site Locations
Total: 11 locations
1
Rady Children's Hospital
San Diego, California, United States, 92123
Actively Recruiting
2
University of Colorado Hopsital - Anschutz Medical Campus
Aurora, Colorado, United States, 80045
Actively Recruiting
3
Kennedy Krieger
Baltimore, Maryland, United States, 21205
Actively Recruiting
4
Boston Children's Hospital
Boston, Massachusetts, United States, 02115
Actively Recruiting
5
Gillette Children's Specialty Healthcare
Saint Paul, Minnesota, United States, 55101
Actively Recruiting
6
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Actively Recruiting
7
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
Actively Recruiting
8
Baylor College of Medicine
Houston, Texas, United States, 77030
Actively Recruiting
9
Kepler University Hospital
Linz, Austria, 4040
Actively Recruiting
10
CHU Dijon Bourgogne
Dijon, France, 21079
Actively Recruiting
11
Hospital Saint Joan de Deu
Barcelona, Spain, 8950
Actively Recruiting
Research Team
I
Ionis Pharmaceuticals
How is the study designed?
Study Type
INTERVENTIONAL
Masking
QUADRUPLE
Allocation
RANDOMIZED
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
4
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