Symptoms and General Pathology

All Conditions

Nervous System Diseases

Nutritional and Metabolic Diseases

Neoplasms

Rare Diseases

Sclerosis

Motor Neuron Disease

Amyotrophic Lateral Sclerosis

Sarcoma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Neurodegenerative Diseases

Neuromuscular Diseases

Spinal Cord Diseases

Central Nervous System Diseases

TDP-43 Proteinopathies

Proteostasis Deficiencies

Metabolic Diseases

Primary Lateral Sclerosis

Soft Tissue Sarcoma

ION363 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.

Placebo 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).

ION363 will be administered by IT bolus injection.

ION363

Placebo will be administered by IT bolus injection.

Placebo

Ionis Pharmaceuticals

The primary purpose of this study is to evaluate the efficacy of ION363 on clinical function and survival in carriers of fused in sarcoma mutations with amyotrophic lateral sclerosis (FUS-ALS).

This is a multi-center, three-part study of ION363 in up to 95 participants. Part 1 will consist of participants who will be randomized in a 2:1 ratio to receive a multi-dose regimen of ION363 or placebo for a period of 60 weeks, followed by Part 2, in which participants will receive open-label ION363 for a period of 84 weeks. Participants may continue to receive open-label ION363 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 ION363 development program, whichever occurs earlier.

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)

A Phase 1-3 Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Intrathecally Administered ION363 in Amyotrophic Lateral Sclerosis Patients With Fused in Sarcoma Mutations (FUS-ALS)

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.

The ALSSQOL-R is a disease-specific 50-item assessment that measures the quality of life. Each item will be rated by the participant on a scale of 0 to 10, with 0 being the least desirable situation and 10 being the most desirable.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
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)	NCT04768972	Amyotrophic Lat...	ION363 Placebo	10 Years -	Ionis Pharmaceuticals, Inc.
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)	NCT04768972	Amyotrophic Lat...	ION363 Placebo	10 Years -	Ionis Pharmaceuticals, Inc.

Spots Global Cancer Trial Database for sarcoma mutations