ClinicalTrials.gov record NCT06430385
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)
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
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
This randomized, quadruple-masked, multiple-ascending dose study evaluates intrathecal ION440 in males with genetically confirmed MECP2 Duplication Syndrome. Part 1 (about 36 weeks) randomizes participants 3:1 to ION440 or a sham lumbar procedure across several dose cohorts and two age subcohorts (ages 8–65 and 2–7) enrolled sequentially. Participants who complete Part 1 may enter Part 2, an open-label long-term extension receiving ION440 for up to approximately 156 weeks.
What it is studying. The study is testing the safety and tolerability of intrathecal ION440 in people with MECP2 Duplication Syndrome and measuring how the drug behaves in the body (pharmacokinetics) and its pharmacodynamic effects. It compares multiple ascending dose levels in a sham-controlled, masked period and collects longer-term data in an open-label extension.
What the researchers hope to learn. Collect safety and tolerability data (treatment-emergent adverse events, vital signs, physical and neurological exams, laboratory assessments, ECG). Characterize pharmacokinetics of ION440 in plasma and CSF (Cmax, AUC, half-life, trough concentrations). Gather longer-term safety and pharmacokinetic data in an open-label extension.
What this study is about
The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.
The primary purpose of this study is to evaluate the safety and tolerability of ION440.
Interventions being studied
Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.
- Drug
- ION440
- Procedure
- Sham procedure
Eligibility
The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.
Inclusion criteria
- for Part 1:
- Males aged ≥ 2 to ≤ 65 years, depending on specific cohort and group, at the time of informed consent.
- Group A: ≥ 8 to ≤ 65 years old
- Group B: 2 to 7 years old, inclusive
- Participant has at least one parent or caregiver ≥ 18 years old capable of providing informed consent and able to comply with all study requirements and activities.
- Participant has a documented diagnosis of MDS with genetic confirmation of MECP2 duplication.
- Is currently receiving stable doses of concomitant medications for at least 1 month prior to screening.
- Able to complete all study procedures, measurements and visits to support primary and secondary endpoints, in the opinion of the Investigator.
- Key
Exclusion criteria
- for Part 1:
- Documented diagnosis of severe MECP2 duplications including terminal duplication and/or translocation or MECP2 triplication OR clinical features associated with severe variant structure including (a) onset of seizures prior to age 5 (for those aged 5 and above at signing of ICF), (b) oxygen dependence, (c) microcephaly, IF MECP2 genetic structure information is unavailable.
- Clinically significant vital sign or ECG abnormality at Screening
- Known brain or spinal disease that would interfere with the LP procedure, or CSF circulation or presence of other factors would affect the safety of the LP procedure.
- Has any concomitant disease or condition or circumstance, or any finding at Screening that, in the opinion of the Investigator, makes the participant unsuitable for enrollment or that could interfere with the conduct of the study or that would pose an unacceptable risk to the participant in this study.
- Treatment with an investigational drug, biological agent, or device within 30 days of Screening, or 5 half-lives of investigational agent, whichever is longer.
- Previous treatment with an oligonucleotide (including siRNA) within 4 months of Screening if single dose received, or within 12 months of Screening if multiple doses received (this exclusion does not apply to vaccines - both mRNA and viral vector vaccines are allowed including COVID-19). For centrally administered ASOs, a minimum of 12 months washout is required irrespective of the number of doses received.
- Currently enrolled in a clinical trial of an investigational agent or device or has used any investigational agent or device within 5 half-lives of investigational agent, whichever is longer.
- Has a history of gene therapy or cell transplantation or any other experimental brain surgery.
- Active infection requiring systemic antiviral or antimicrobial therapy that will not be completed prior to Baseline (Day 1).
- Has experienced Status Epilepticus in the past 6 months.
- Key Inclusion criteria for Part 2:
- Participants in ION440-CS1, Part 1/MAD who received at least one dose of Study Drug /Sham in Part 1/MAD, missed no more than 1 study visit, and attended the Follow Up visit (Visit 6).
- All inclusion criteria in Part 1/MAD apply (participants will not be required to undergo new Screening bloodwork).
- Key Exclusion criteria for Part 2:
- Has developed any concomitant disease (e.g., gastrointestinal, renal, hepatic, endocrine, respiratory, or cardiovascular system disease) or condition or circumstance, or any finding during Part 1/MAD that, in the opinion of the Investigator, makes the participant unsuitable for continued treatment (e.g., could interfere with the conduct of the study or that would pose an unacceptable risk to the participant in this study).
Study description and what participation involves
The study's detailed description, as published on ClinicalTrials.gov.
Detailed description from the registry
This is a phase 1-2 randomized, double-blind, sham-controlled, multiple-ascending dose (MAD) study to evaluate ION440 in pediatric and adult participants with MECP2 Duplication Syndrome (MDS) and will be conducted in two parts. During Part 1 (MAD) (36 weeks), participants will be randomized in a 3:1 ratio to receive ION440 or sham. Individuals who complete Part 1 may enter Part 2, an open label long-term extension study (LTE), where they will receive ION440 for up to approximately 156 weeks. Multiple dose cohorts (Dose A, Dose B, and Dose C) will be evaluated in the study. All dosing cohorts will be further subdivided by age. Sub cohort A will include participants 8 through 65 years of age, and sub cohort B will include participants 2 through 7 years of age. Dosing cohorts will be enrolled sequentially with sub cohort A initiating prior to sub cohort B.
AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
In Part 1 (about 36 weeks) participants are randomized (3:1) to receive intrathecal ION440 or a sham procedure; the sham includes a lumbar puncture with CSF collection but no drug injection. Study visits include repeated lumbar punctures (spinal taps) for CSF collection and, for treated participants, intrathecal dosing, plus regular blood draws for drug levels and safety tests. Participants will have routine safety monitoring such as vital signs, ECGs, and physical and neurological exams at multiple visits. Those who complete Part 1 may enter an open‑label extension to receive ION440 for longer-term follow-up.
How the study is structured. Interventional, randomized, multiple-ascending dose study. Part 1 is quadruple-masked and randomizes participants 3:1 to receive intrathecal ION440 or a sham lumbar procedure; dose cohorts (A, B, C) are evaluated sequentially and each cohort is divided into two age subcohorts (≥8–65 years and 2–7 years). Part 2 is an open-label long-term extension where participants receive ION440 for up to about 156 weeks.
Questions you could ask
These questions are suggestions for a conversation with the study team or your own clinician, not advice.
- The registry lists this study under Methyl CpG Binding Protein 2 (MECP2) Duplication Syndrome. Does it apply to my diagnosis?
- This is an early-phase study, mainly about safety and dose. What is already known about this treatment?
- The listed sites are in Austria, Canada, France, Spain, United States. Is any of them reachable for me, and does the study help with travel?
- Which of the eligibility criteria would need to be checked with tests before I could join?
More on Rett syndrome
Important dates
- Study start
- Oct 21, 2024
- Primary completion
- September 2027 (estimated)
- Study completion
- April 2030 (estimated)
- Target enrollment
- 48 participants (estimated)
- Last updated on registry
- Oct 8, 2026
- Data verified
- Oct 10, 2026
Sponsor and research team
The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.
- Lead sponsor
- Ionis Pharmaceuticals, Inc.
Central study contact
If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.
- Ionis Pharmaceuticals 📞 (844) 779-1497 ✉ IonisMECP2study@clinicaltrialmedia.com
Participating sites (12)
- Rady Children's HospitalRecruiting
San Diego, California, 92123 · United States
- University of Colorado Hopsital - Anschutz Medical CampusRecruiting
Aurora, Colorado, 80045 · United States
- Kennedy KriegerRecruiting
Baltimore, Maryland, 21205 · United States
- Boston Children's HospitalRecruiting
Boston, Massachusetts, 02115 · United States
- Gillette Children's Specialty HealthcareRecruiting
Saint Paul, Minnesota, 55101 · United States
- Children's Hospital of PhiladelphiaRecruiting
Philadelphia, Pennsylvania, 19104 · United States
- Vanderbilt University Medical CenterRecruiting
Nashville, Tennessee, 37232 · United States
- Baylor College of MedicineRecruiting
Houston, Texas, 77030 · United States
- Kepler University HospitalRecruiting
Linz, 4040 · Austria
- British Columbia Children's HospitalRecruiting
Vancouver, V6H3V4 · Canada
Terms used on this page · explanations by MedicalUpdates.ai
- primary purpose
- The main reason an interventional study is being done, for example treatment, prevention, diagnosis, supportive care or basic science.
- cohort
- A group of people who share a characteristic, such as a diagnosis, and are studied together. 'Prospective' means they are followed forward from enrolment; 'retrospective' means existing records are reviewed.
- informed consent
- The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
- concomitant medications
- Other medicines a participant takes during the study. Some must be reported; some are restricted.
- prior to screening
- The checks done before enrolment to see whether a person qualifies, such as tests, scans or a review of medical history.
- endpoints
- Something the study measures to judge its results, such as a symptom score, a blood test or survival. Outcomes are grouped as primary, secondary and sometimes exploratory.
- ECG
- A recording of the heart's electrical activity. QTc is one measurement from it; some drugs are avoided if it is prolonged.
- enrollment
- The number of participants a study plans to include, or has included. 'Estimated' means the planned number; 'actual' means the number who joined.
- investigational drug
- A treatment that is being tested and has not been approved for this use. It may be approved for a different condition. Being studied does not mean it works or is available outside the study.
- 5 half-lives
- The time it takes for the amount of a drug in the body to fall by half. 'Five half-lives' is often used as the point at which a previous drug has essentially left the body.
- washout
- A period during which a participant stops a previous treatment before starting the study treatment, so the earlier treatment does not affect the results.
- Baseline
- Measurements taken at the start of the study, before any study treatment, so that later results can be compared with them.
- Key Inclusion criteria
- The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
- Sham
- A procedure designed to resemble the real procedure, for example the same visit and equipment, without its active part. It is the procedure equivalent of a placebo.
- Follow Up
- The period after treatment or enrolment during which participants are observed or contacted, for example to record side effects or outcomes.
- Key Exclusion criteria
- The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
- phase 1
- An early-stage study, usually small, mainly to check safety, side effects and how much of a treatment can be given. Whether it works is not the main question yet.
- randomized
- Participants are assigned to the study groups by chance, like a coin toss, rather than chosen by the doctor or the participant. This is done so the groups are comparable.
- double-blind
- Two types of people involved in the study do not know which intervention a participant is receiving. The ClinicalTrials.gov record specifies who is masked, for example participants, care providers, investigators or outcome assessors.
- ascending dose
- Groups of participants receive increasing doses of a treatment, one group after another, to find a dose that can be given safely.
- 3:1
- How many participants go to each group. In a 2:1 ratio, two are assigned to the first group for every one assigned to the second.
- open label
- No masking is used, so the assigned intervention is not deliberately hidden from participants or study staff.
- extension study
- A continuation study in which participants who completed an earlier study can keep receiving the treatment, usually with everyone knowing what they are given.
The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.
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