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ION440

Phase 1

Methyl CpG Binding Protein 2 (MECP2) Duplication Syndrome | Small molecule | Rare Disease |Ionis Pharmaceuticals, Inc.|Last Updated: Mar 24, 2026

Target and mechanism

Molecular targetMECP2
ModalitySmall molecule

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindSHAM_CONTROLLEDDMC
Total Trials1
Total Enrollment48

FDA Designations

No designations recorded

Clinical trial landscape

ION440 · 1 trial · 1 indication

Phase 1 1
NCT06430385ATTUNE: 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)Methyl CpG Binding Protein 2 (MECP2) Duplication Syndrome
RECRUITING48 Analytics
PHASE1RECRUITING
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)
Methyl CpG Binding Protein 2 (MECP2) Duplication SyndromeUnlock trial analytics

Study Endpoints

Primary Endpoints

Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Up to approximately 36 weeks
Part 1: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Baseline up to approximately 36 weeks
Part 1: Number of Participants With Clinically Significant Change From Baseline in Physical and Neurological Examination Findings
Baseline up to approximately 36 weeks
Part 1: Number of Participants With Clinically Significant Change from Baseline in Laboratory Assessments
Baseline up to approximately 36 weeks
Part 1: Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG)
Baseline up to approximately 36 weeks
Part 2: Number of Participants With TEAEs
Up to approximately 192 weeks
Part 2: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Baseline up to approximately 192 weeks
Part 2: Number of Participants With Clinically Significant Change From Baseline in Physical and Neurological Examination Findings
Baseline up to approximately 192 weeks
Part 2: Number of Participants With Clinically Significant Change from Baseline in Laboratory Assessments
Baseline up to approximately 192 weeks
Part 2: Number of Participants With Clinically Significant Change From Baseline in ECG
Baseline up to approximately 192 weeks

Secondary Endpoints

Part 1: Maximum Observed Concentration (Cmax) of ION440 in Plasma
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
Pre-dose and at multiple points post-dose up to Week 36
Part 1: Plasma Terminal Elimination Half-life (t½) of ION440
Pre-dose and at multiple points post-dose up to Week 36
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Study Design & Arms

AllocationRANDOMIZED
MaskingQUADRUPLE
ModelSEQUENTIAL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Cohort 1: ION440 Dose AEXPERIMENTALParticipants will receive ION440 intrathecally at Dose A during Part 1/MAD, followed by ION440 Dose A during Part 2/LTE.
Cohort 2: ION440 Dose BEXPERIMENTALParticipants will receive ION440 intrathecally at Dose B during Part 1/MAD, followed by ION440 Dose B during Part 2/LTE.
Cohort 3: ION440 Dose CEXPERIMENTALParticipants will receive ION440 intrathecally at Dose C during Part 1/MAD, followed by ION440 Dose C during Part 2/LTE.
Sham ProcedureSHAM_COMPARATORDuring 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).

Interventions

NameTypeDescription
ION440DRUGION440 will be administered by intrathecal bolus (ITB) injection.
Sham procedurePROCEDUREAn LP will be performed with CSF collection but will not be followed by the administration of study treatment by ITB injection.
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Eligibility Criteria

Age Range2 Years to 65 Years
SexMALE
Healthy VolunteersNo
Study Sites11

Key Inclusion criteria for Part 1: 1. Males aged ≥ 2 to ≤ 65 years, depending on specific cohort and group, at the time of informed consent. 1. Group A: ≥ 8 to ≤ 65 years old 2. Group B: 2 to 7 years old, inclusive 2. Participant has at least one parent or caregiver ≥ 18 years old capable of...

Countries:United StatesAustriaFranceSpain
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Frequently asked questions about ION440

What is ION440 used for?

ION440 is an investigational drug being developed for Methyl CpG Binding Protein 2 (MECP2) Duplication Syndrome, a rare genetic disorder. It is administered intrathecally and is currently in Phase 1 clinical development. The drug is not yet approved and remains under study for safety, tolerability, pharmacokinetics, and pharmacodynamics.

What does ION440 target?

ION440 targets MECP2, the Methyl CpG Binding Protein 2 gene. By targeting MECP2, the drug aims to address the underlying cause of MECP2 Duplication Syndrome. The drug is a small molecule designed for intrathecal administration to reach the central nervous system.

Who makes ION440?

ION440 is developed by Ionis Pharmaceuticals, Inc., a biopharmaceutical company traded on NASDAQ under the ticker IONS. The company is conducting a Phase 1 clinical trial to evaluate the drug in patients with MECP2 Duplication Syndrome.

What phase is ION440 in?

ION440 is in Phase 1 clinical development. It is an investigational drug, not yet approved by regulatory authorities. The ongoing Phase 1 trial, NCT06430385, is recruiting participants to assess the drug's safety, tolerability, pharmacokinetics, and pharmacodynamics in patients with MECP2 Duplication Syndrome.

What clinical trials is ION440 in?

ION440 is being studied in a Phase 1 clinical trial with the identifier NCT06430385, titled ATTUNE. This randomized, double-blind, sham-controlled study is recruiting 48 male participants aged 2 years and older with MECP2 Duplication Syndrome. The trial is conducted in the United States, Austria, France, and Spain.