Ionis FUS-ALS trial

A Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Intrathecally Administered IMP in Amyotrophic Lateral Sclerosis Patients with Fused in Sarcoma Mutations (FUS-ALS) 

UK Chief Investigator

Professor Chris Shaw

Research summary

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease. Patients suffer with loss of muscle mass, strength, and function in bulbar, respiratory, and voluntary muscle. Decline is inevitable, with death from respiratory failure following 2 to 5 years after diagnosis for most patients. ALS-associated Fused in Sarcoma (FUS) mutations are often associated with a more severe course compared to ALS patients associated with other genetic mutations.

It is a severe disorder with no available disease-modifying treatment. The only currently approved treatments for ALS are riluzole and edaravone. Riluzole provides a modest increase in survival (2 to 3 months) without noticeable improvement in strength or disability. The effect of edaravone on survival is unknown. No specific FUS-ALS treatments are available. For these reasons, there is a substantial unmet medical need to delay or prevent further progression of this devastating disease.

The primary purpose of this study is to evaluate the clinical efficacy of ION363 in clinical functioning and survival in FUS-ALS patients. Ionis Pharmaceuticals, Inc. is developing ION363 for the treatment of ALS patients with FUS mutation. ION363 is a drug that selectively targets a specific region of the FUS pre-messenger ribonucleic acid (pre-mRNA), thereby reducing FUS mRNA which encodes FUS protein expression. The reduction of toxic mutant FUS protein may delay, halt, or even reverse disease progression in FUS-ALS patients.

This is a Phase 1-3, global, multi-center, two-part study. Part 1 will consist of participants (maximum of 63 patients) that will be randomized in a 2:1 ratio to receive a multi-dose regimen of ION363 or placebo for 29 weeks treatment period, followed by Part 2, which will be an open-label extension study where all participants will receive ION363 for 77 weeks treatment period. Currently, only one site is selected in the United Kingdom.

Current status

Open to recruitment

Recruitment target

3 participants in the UK; up to 44 participants globally

Recruitment group(s)

Patients with MND


King's College Hospital

Information about study sites

Contact details

Key dates

Recruitment open date : 30 December 2021

Planned recruitment close date: 01 September 2025

Inclusion / exclusion criteria

Inclusion criteria

Inclusion Criteria for Part 1:

Inclusion Criteria for Part 2:

Exclusion criteria

Exclusion Criteria for Part 1:


Ionis Pharmaceuticals, Inc.


Ionis Pharmaceuticals, Inc.

Study design

Interventional (drug), randomised controlled trial




Outcome measures

Primary outcome measure

Change from Baseline (Day 1) through Study Day 505 in Part 1 in 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), time of rescue or discontinuation from Part 1 and entering Part 2 due to a deterioration in function, and Ventilation Assistance-free survival (VAFS). 

Secondary outcome measures