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ION356

Phase 1

Pelizaeus-Merzbacher Disease | Small molecule | Rare Disease |Ionis Pharmaceuticals, Inc.|Last Updated: Dec 12, 2025

Target and mechanism

Molecular targetPLP1
ModalitySmall molecule

Success Probability

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Market & Valuation

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Trial Design

RandomizedCONTROLLED
Total Trials1
Total Enrollment24

FDA Designations

No designations recorded

Clinical trial landscape

ION356 · 1 trial · 1 indication

Phase 1 1
NCT06150716Orbit Study: A Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Intrathecally Administered ION356 in Participants With Pelizaeus Merzbacher Disease (PMD)Pelizaeus-Merzbacher Disease
RECRUITING24 Analytics
PHASE1RECRUITING
Orbit Study: A Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Intrathecally Administered ION356 in Participants With Pelizaeus Merzbacher Disease (PMD)
Pelizaeus-Merzbacher DiseaseUnlock trial analytics

Study Endpoints

Primary Endpoints

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
Up to Week 145
Number of Participants With Clinically Significant Change from Baseline in Laboratory Assessments
Baseline up to Week 145
Number of Participants With Clinically Significant Change From Baseline in Neurological Examination Findings
Baseline up to Week 145
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Baseline up to Week 145
Number of Participants With Clinically Significant Change From Baseline in Electrocardiography (ECG)
Baseline up to Week 145
Number of Participants With Change From Baseline in Concomitant Medication Use
Baseline up to Week 145

Secondary Endpoints

Maximum Plasma Concentration (Cmax) of ION356
Pre-dose and at multiple points post-dose up to Week 145
Area Under the Concentration-time Curve (AUC) of ION356
Pre-dose and at multiple points post-dose up to Week 145
Plasma Terminal Elimination Half-life (t½) of ION356
Pre-dose and at multiple points post-dose up to Week 145
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Study Design & Arms

AllocationRANDOMIZED
MaskingNONE
ModelSEQUENTIAL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Cohort A: ION356 Dose AEXPERIMENTALParticipants will receive ION356 intrathecally at Dose A in the MAD Period, followed by ION356 Dose A in the LTE Period.
Cohort B: ION356 Dose BEXPERIMENTALParticipants will receive ION356 intrathecally at Dose B in the MAD Period, followed by ION356 Dose B in the LTE Period.

Interventions

NameTypeDescription
ION356DRUGAdministered as intrathecal (IT) injection.
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Eligibility Criteria

Age Range2 Years to 17 Years
SexMALE
Healthy VolunteersNo
Study Sites7

Key Inclusion Criteria 1. Participant's parent or legally accepted representative can provide informed consent, attend all scheduled study visits, provide feedback regarding the participant's symptoms, and can comply with all study requirements. 2. Diagnosis of PMD with genetic confirmation of PLP1...

Countries:United StatesFranceGermanyJapanNetherlands
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Frequently asked questions about ION356

What is ION356 used for?

ION356 is an investigational small molecule being developed for Pelizaeus-Merzbacher Disease (PMD), a rare genetic disorder. It is administered intrathecally and is currently in Phase 1 clinical development. The drug is designed to target the PLP1 gene, which is implicated in the condition.

What does ION356 target?

ION356 targets PLP1, the gene associated with Pelizaeus-Merzbacher Disease. By modulating PLP1, the drug aims to address the underlying genetic cause of the disease. It is administered intrathecally to deliver the therapy directly to the central nervous system.

Who makes ION356?

ION356 is being 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's safety, pharmacokinetics, and pharmacodynamics in participants with Pelizaeus-Merzbacher Disease.

What phase is ION356 in?

ION356 is in Phase 1 clinical development. It is an investigational drug and has not been approved by regulatory authorities. The ongoing Phase 1 trial, known as the Orbit Study, is currently recruiting participants with Pelizaeus-Merzbacher Disease.

What clinical trials is ION356 in?

ION356 is being evaluated in the Orbit Study (NCT06150716), a Phase 1 trial assessing the safety, pharmacokinetics, and pharmacodynamics of intrathecally administered ION356 in participants with Pelizaeus-Merzbacher Disease. The trial is recruiting 24 male participants aged 2 years and older across the United States, France, Germany, Japan, and the Netherlands.