A Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of ION363 in FUS-ALS
Research type
Research Study
Full title
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)
IRAS ID
1003814
Contact name
James Bashford
Contact email
Sponsor organisation
Ionis Pharmaceuticals, Inc.
Eudract number
2020-005522-28
Clinicaltrials.gov Identifier
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.
REC name
London - Westminster Research Ethics Committee
REC reference
21/LO/0428
Date of REC Opinion
5 Aug 2021
REC opinion
Further Information Favourable Opinion