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ION363

Phase 3

Amyotrophic Lateral Sclerosis | Small molecule | Neurology |Ionis Pharmaceuticals, Inc.|Last Updated: Jul 21, 2026

Success Probability

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLEDDMC
Total Trials1
Total Enrollment89

FDA Designations

No designations recorded

Clinical trial landscape

ION363 · 1 trial · 1 indication

Phase 3 1
NCT04768972FUSION: A Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of ION363 in Amyotrophic Lateral Sclerosis Participants With Fused in Sarcoma Mutations (FUS-ALS)Amyotrophic Lateral Sclerosis
ACTIVE NOT_RECRUITING89 Analytics
PHASE3ACTIVE NOT_RECRUITING
FUSION: A Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of ION363 in Amyotrophic Lateral Sclerosis Participants With Fused in Sarcoma Mutations (FUS-ALS)
Amyotrophic Lateral SclerosisUnlock trial analytics

Study Endpoints

Primary Endpoints

Change from Baseline (Day 1) through Study Day 505 in Part 1 in functional impairment
Baseline, Day 505 in Part 1

Functional impairment to be measured by joint rank analysis of the combined assessment of: In-clinic Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) total score, time of rescue or discontinuation from Part 1 and entering Part 2 due to a deterioration in function, and ventilation assistance-free survival (VAFS). ALSFRS-R measures functional disease severity. The scale measures four functional domains, bulbar function, gross motor skills, fine motor skills, and respiratory function. The assessment will contain 12 questions scored from 0 (no function) to 4 (full function), with a total possible score of 48, which will indicate the highest level of function. ALSFRS-R will be a part of the combined assessment of joint rank analysis to assess efficacy in Part 1.

Secondary Endpoints

Change from Baseline in ALS Assessment Questionnaire, 5-item (ALSAQ-5)
Baseline, Day 505 in Part 1
Change from Baseline in the in-clinic Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R)
Baseline, Day 505 in Part 1
Survival and Ventilation Assistance-Free Survival (VAFS)
Up to Day 505 in Part 1
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Study Design & Arms

AllocationRANDOMIZED
MaskingDOUBLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
ION363EXPERIMENTALION363 will be administered by lumbar intrathecal (IT) bolus injection every 12 weeks, with an additional loading dose at 4 weeks, over a 60-week double-blind treatment period in Part 1; every 12 weeks for 84 weeks in the open-label extension treatment period (Part 2), with an additional loading dose administered 4 weeks after the first dose. Patients may continue to receive open-label ION363 every 12 weeks in Part 3 for up to 3 additional years or until ION363 becomes commercially available in the patient's country or until the Sponsor discontinues the development program, whichever occurs earlier.
PlaceboPLACEBO_COMPARATORPlacebo will be administered by lumbar IT bolus injection every12 weeks, with an additional loading dose at 4 weeks, over a 60-week double-blind treatment period (Part 1).

Interventions

NameTypeDescription
ION363DRUGION363 will be administered by IT bolus injection.
PlaceboDRUGPlacebo will be administered by IT bolus injection.
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Eligibility Criteria

Age Range10 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites25

Inclusion Criteria for Part 1: 1. Participants must be ≥10 years of age at the time of informed consent and have signs or symptoms consistent with an ALS disease (in the opinion of the Investigator). 2. Genetic mutation in FUS confirmed by a testing laboratory that is Clinical Laboratory Improvemen...

Countries:United StatesBelgiumBrazilCanadaGermanyIrelandItalyJapanNetherlandsPolandSouth KoreaSpainSwedenSwitzerlandTaiwanUnited Kingdom
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Recent Changes (Last 90 Days)

LOWJul 21, 2026NCT04768972primaryCompletionDate: changed
LOWMay 26, 2026NCT04768972primaryCompletionDate: changed
LOWMay 24, 2026NCT04768972studyFirstPostDate: changed

Frequently asked questions about ION363

What is ION363 used for?

ION363 is an investigational drug being studied for the treatment of Amyotrophic Lateral Sclerosis (ALS) in patients with Fused in Sarcoma (FUS) mutations, a condition known as FUS-ALS. It is currently in Phase 3 clinical development and has not been approved by regulatory authorities.

What does ION363 target?

ION363 is designed to target the Fused in Sarcoma (FUS) gene, which is mutated in a subset of ALS patients. By targeting this genetic cause, the drug aims to address the underlying pathology of FUS-ALS. It is being evaluated in patients with confirmed FUS mutations.

Who makes ION363?

ION363 is being developed by Ionis Pharmaceuticals, Inc., a biopharmaceutical company traded on NASDAQ under the ticker symbol IONS. The company is conducting a Phase 3 clinical trial to evaluate the drug's efficacy and safety in patients with FUS-ALS.

What phase is ION363 in?

ION363 is currently in Phase 3 clinical development. It is being studied in a randomized, double-blind, placebo-controlled trial. The drug is investigational and has not yet been approved for any use. Its safety and efficacy are still being evaluated in clinical trials.

What clinical trials is ION363 in?

ION363 is being evaluated in a Phase 3 trial with the identifier NCT04768972, known as the FUSION study. This trial is assessing the efficacy, safety, pharmacokinetics, and pharmacodynamics of ION363 in ALS participants with FUS mutations. The trial is active but not recruiting, with an enrollment of 89 participants.

Is ION363 the same as FUSION?

No, ION363 is the drug being studied, while FUSION is the name of the clinical trial evaluating it. The FUSION trial, with the identifier NCT04768972, is a Phase 3 study of ION363 in patients with ALS who have FUS mutations. The trial is active but not recruiting participants.