Methyl CpG Binding Protein 2 (MECP2) Duplication SyndromePhase 1/2NCT06430385
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 study testing ION440 in people with Methyl CpG Binding Protein 2 (MECP2) Duplication Syndrome, run by Ionis Pharmaceuticals, Inc. at 12 sites in 5 countries.
Trial summary
The primary purpose of this study is to evaluate the safety and tolerability of ION440. Read more about this study
- Who is it for?
- Ages 2 to 65 years, men only
- Conditions the study is for
- Methyl CpG Binding Protein 2 (MECP2) Duplication Syndrome
- What is being tested?
- ION440
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 12 sitesin 5 countries
- Study dates
- 21 Oct 2024to Apr 2030
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 65 years
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
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- Able to complete all study procedures, measurements and visits to support primary and secondary endpoints, in the opinion of the Investigator.
- 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).
Who cannot join
- 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.
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- 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.
- 1. 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).
Trial locations and contacts
12 sites in 5 countries. Contact the study team or a site near you to ask about taking part.
12 sites in 5 countries
United States8 sites, 8 recruiting
- Recruiting
University of Colorado Hopsital - Anschutz Medical Campus
Aurora, Colorado, 80045
- Recruiting
Kennedy Krieger
Baltimore, Maryland, 21205
- Recruiting
Boston Children's Hospital
Boston, Massachusetts, 02115
- Recruiting
Baylor College of Medicine
Houston, Texas, 77030
- Recruiting
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
- Recruiting
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
- Recruiting
Gillette Children's Specialty Healthcare
Saint Paul, Minnesota, 55101
- Recruiting
Rady Children's Hospital
San Diego, California, 92123
Canada1 site, 1 recruiting
- Recruiting
British Columbia Children's Hospital
Vancouver, V6H3V4
About this study
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
The primary purpose of this study is to evaluate the safety and tolerability of ION440.
Read the detailed description
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.
- Being tested
- ION440, Sham procedure
- Medical subject headings
- Rett Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ION440Drug
ION440 will be administered by intrathecal bolus (ITB) injection.
Sham procedureProcedure or surgery
An LP will be performed with CSF collection but will not be followed by the administration of study treatment by ITB injection.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: ION440 Dose A | Experimental | Participants will receive ION440 intrathecally at Dose A during Part 1/MAD, followed by ION440 Dose A during Part 2/LTE. Receives: Drug: ION440 |
| Cohort 2: ION440 Dose B | Experimental | Participants will receive ION440 intrathecally at Dose B during Part 1/MAD, followed by ION440 Dose B during Part 2/LTE. Receives: Drug: ION440 |
| Cohort 3: ION440 Dose C | Experimental | Participants will receive ION440 intrathecally at Dose C during Part 1/MAD, followed by ION440 Dose C during Part 2/LTE. Receives: Drug: ION440 |
| Sham Procedure | Sham comparator | During the Part 1/MAD period, a lumbar procedure (LP) will be performed at the same frequency as ION440 administration. Participants will not receive ITB injections during this period. It will be followed by the open-label Part 2/LTE period, where participants will receive ION440 at the same dose as their enrolled cohort (e.g. Dose A, Dose B or Dose C). Receives: Procedure: Sham procedure |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Measured: Up to approximately 36 weeks
Part 1: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Measured: Baseline up to approximately 36 weeks
Part 1: Number of Participants With Clinically Significant Change From Baseline in Physical and Neurological Examination Findings
Measured: Baseline up to approximately 36 weeks
Part 1: Number of Participants With Clinically Significant Change from Baseline in Laboratory Assessments
Measured: Baseline up to approximately 36 weeks
Part 1: Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG)
Measured: Baseline up to approximately 36 weeks
Part 2: Number of Participants With TEAEs
Measured: Up to approximately 192 weeks
Part 2: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Measured: Baseline up to approximately 192 weeks
Part 2: Number of Participants With Clinically Significant Change From Baseline in Physical and Neurological Examination Findings
Measured: Baseline up to approximately 192 weeks
Part 2: Number of Participants With Clinically Significant Change from Baseline in Laboratory Assessments
Measured: Baseline up to approximately 192 weeks
Part 2: Number of Participants With Clinically Significant Change From Baseline in ECG
Measured: Baseline up to approximately 192 weeks
Secondary outcomes (6)
Part 1: Maximum Observed Concentration (Cmax) of ION440 in Plasma
Measured: Pre-dose and at multiple points post-dose up to Week 36
Part 1: Area Under the Concentration-time Curve (AUC) of ION440 in Plasma
Measured: Pre-dose and at multiple points post-dose up to Week 36
Part 1: Plasma Terminal Elimination Half-life (t½) of ION440
Measured: Pre-dose and at multiple points post-dose up to Week 36
Part 1: Trough Concentration (Ctrough) of ION440 in Plasma and CSF
Measured: Pre-dose and at multiple points post-dose up to Week 36
Part 1: Plasma Concentration of ION440
Measured: Pre-dose and at multiple points post-dose up to Week 36
Part 2: Trough Concentration (Ctrough) of ION440 in Plasma and CSF
Measured: Up to approximately 192 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 May 2024
- Study start21 Oct 2024
- Primary completionSep 2027 (estimated)
- Study completionApr 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Methyl CpG Binding Protein 2 (MECP2) Duplication SyndromeStudies of the same condition, open and under way.
- More trials run by Ionis Pharmaceuticals, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ionis Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06430385
- Sponsor's protocol ID
- ION440-CS1
- Other IDs
- 2023-507192-22, U1111-1303-4105, 2023
- Status last verified
- Oct 2026
- First submitted
- 21 May 2024
- Last updated
- 8 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Ionis may share anonymized individual participant data, aggregated clinical data, and other types of data that support the results in this study. Data requests from qualified researchers will be considered once all three of the following criteria are met: (1) 12 months from marketing approval of the study drug in both the United States and European Union; (2) 18 months from conclusion of the study; and (3) 6 months from publication of study article. Access would be via a secure environment and is contingent upon approval of a research proposal and entry into an appropriate data use agreement. Requests to access data can be submitted via the website https://vivli.org/ourmember/ionis/.
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT06430385
- Acronym / sponsor ID
- ION440-CS1
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- Ionis Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 21 Oct 2024 (actual)
- Primary completion
- Sep 2027 (estimated)
- Study completion
- Apr 2030 (estimated)
- First posted
- 28 May 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary purpose of this study is to evaluate the safety and tolerability of ION440.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: ION440 Dose A | Experimental | Drug: ION440Participants will receive ION440 intrathecally at Dose A during Part 1/MAD, followed by ION440 Dose A during Part 2/LTE. |
| Cohort 2: ION440 Dose B | Experimental | Drug: ION440Participants will receive ION440 intrathecally at Dose B during Part 1/MAD, followed by ION440 Dose B during Part 2/LTE. |
| Cohort 3: ION440 Dose C | Experimental | Drug: ION440Participants will receive ION440 intrathecally at Dose C during Part 1/MAD, followed by ION440 Dose C during Part 2/LTE. |
| Sham Procedure | Sham comparator | Procedure: Sham procedureDuring the Part 1/MAD period, a lumbar procedure (LP) will be performed at the same frequency as ION440 administration. Participants will not receive ITB injections during this period. It will be followed by the open-label Part 2/LTE period, where participants will receive ION440 at the same dose as their enrolled cohort (e.g. Dose A, Dose B or Dose C). |
Who may qualify
- Ages
- 2 to 65 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- Males aged ≥ 2 to ≤ 65 years, depending on specific cohort and group, at the time of informed consent.
- 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 (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ION440ION440 will be administered by intrathecal bolus (ITB) injection. | Drug | Cohort 1: ION440 Dose A, Cohort 2: ION440 Dose B, Cohort 3: ION440 Dose C |
| Sham procedureAn LP will be performed with CSF collection but will not be followed by the administration of study treatment by ITB injection. | Procedure or surgery | Sham Procedure |
Primary outcome
Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time frame: Up to approximately 36 weeks
Part 1: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Time frame: Baseline up to approximately 36 weeks
Part 1: Number of Participants With Clinically Significant Change From Baseline in Physical and Neurological Examination Findings
Time frame: Baseline up to approximately 36 weeks
Part 1: Number of Participants With Clinically Significant Change from Baseline in Laboratory Assessments
Time frame: Baseline up to approximately 36 weeks
Part 1: Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG)
Time frame: Baseline up to approximately 36 weeks
Part 2: Number of Participants With TEAEs
Time frame: Up to approximately 192 weeks
Part 2: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Time frame: Baseline up to approximately 192 weeks
Part 2: Number of Participants With Clinically Significant Change From Baseline in Physical and Neurological Examination Findings
Time frame: Baseline up to approximately 192 weeks
Part 2: Number of Participants With Clinically Significant Change from Baseline in Laboratory Assessments
Time frame: Baseline up to approximately 192 weeks
Part 2: Number of Participants With Clinically Significant Change From Baseline in ECG
Time frame: Baseline up to approximately 192 weeks
6 secondary outcomes
Part 1: Maximum Observed Concentration (Cmax) of ION440 in Plasma
Time frame: Pre-dose and at multiple points post-dose up to Week 36
Part 1: Area Under the Concentration-time Curve (AUC) of ION440 in Plasma
Time frame: Pre-dose and at multiple points post-dose up to Week 36
Part 1: Plasma Terminal Elimination Half-life (t½) of ION440
Time frame: Pre-dose and at multiple points post-dose up to Week 36
Part 1: Trough Concentration (Ctrough) of ION440 in Plasma and CSF
Time frame: Pre-dose and at multiple points post-dose up to Week 36
Part 1: Plasma Concentration of ION440
Time frame: Pre-dose and at multiple points post-dose up to Week 36
Part 2: Trough Concentration (Ctrough) of ION440 in Plasma and CSF
Time frame: Up to approximately 192 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2026.
- Individual participant dataSharing planned: Yes. Ionis may share anonymized individual participant data, aggregated clinical data, and other types of data that support the results in this study. Data requests from qualified researchers will be considered once all three of the following criteria are met: (1) 12 months from marketing approval of the study drug in both the United States and European Union; (2) 18 months from conclusion of the study; and (3) 6 months from publication of study article. Access would be via a secure environment and is contingent upon approval of a research proposal and entry into an appropriate data use agreement. Requests to access data can be submitted via the website https://vivli.org/ourmember/ionis/.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
12 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ION440 in people with Methyl CpG Binding Protein 2 (MECP2) Duplication Syndrome, run by Ionis Pharmaceuticals, Inc. at 12 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 8 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States, Austria, Canada, France, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ionis Pharmaceuticals ((844) 779-1497, IonisMECP2study@clinicaltrialmedia.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (time frame: Up to approximately 36 weeks). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2026.