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
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 (where participants may receive ION373 or a placebo) and an Open-Label Treatment Period (where participants will receive ION373).
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 completing questionnaires, physical exams, neurological examinations, ECGs, blood sample collections and MRI scans.
REC name
South Central - Hampshire A Research Ethics Committee
REC reference
21/SC/0013
Date of REC Opinion
22 Jan 2021
REC opinion
Unfavourable Opinion