To evaluate safety and efficacy of ION373 in Alexander Disease
Research type
Research Study
Full title
A Phase 1-3, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Intrathecally Administered ION373 in Patients with Alexander Disease
IRAS ID
287809
Contact name
Jeremy Chataway
Contact email
Sponsor organisation
Ionis Pharmaceuticals, Inc.
Eudract number
2020-000976-40
Clinicaltrials.gov Identifier
Duration of Study in the UK
4 years, 6 months, 0 days
Research summary
This is a phase 1-3 study assessing the safety and effectiveness of ION373 (Study Medication) in patients with Alexander Disease. The study consists of 2 periods: a Double-Blind Treatment Period (60 weeks) where participants are randomised to receive ION373 or a placebo in a 2:1 ratio, followed by an Open-Label Treatment Period (60 weeks) where all participants will receive ION373. Up to three different dose levels will be tested, with the patients enrolled in ascending dose-level cohorts. Since randomisation will occur in a 2:1 ratio, more participants will receive ION373 than placebo during the double-blind period
Alexander disease is caused by an error in the glial fibrillary acidic protein (GFAP) gene, which is the region in the DNA (genetic material) that contains the instructions for the production of a protein with the same name (GFAP). These errors in the genetic instructions lead to over production of GFAP in the brain and spinal cord. The excess GFAP accumulates in the form of protein aggregates known as Rosenthal fibres that cause cell malfunction and death. This is thought to cause the destruction of the myelin sheath, a fatty covering that surrounds and protects nerve fibres. Destruction of myelin leads to the symptoms associated with Alexander disease. The intended effect of ION373 is to reduce GFAP levels, thereby avoiding further destruction of the myelin sheath and potentially altering the course of disease symptoms. Currently, there are no medications approved for the treatment of Alexander disease.
Approximately 42-58 participants (male and female, aged 2 to 65) are planned to be enrolled in this study globally. Participants will take part for approximately 155 weeks (about 3 years), and will undergo procedures such as performance procedures, completing questionnaires, physical exams, neurological examinations, ECGs, blood sample collections and MRI scans.
REC name
London - Hampstead Research Ethics Committee
REC reference
21/LO/0379
Date of REC Opinion
4 Aug 2021
REC opinion
Further Information Favourable Opinion