Phase 1/2 Study of ION582 in Patients with Angelman Syndrome
Research type
Research Study
Full title
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Intrathecally Administered ION582 in Patients with Angelman Syndrome
IRAS ID
1004362
Contact name
Eric Obiri-Asante
Contact email
Sponsor organisation
Ionis Pharmaceuticals, Inc.
Eudract number
2021-003009-23
Clinicaltrials.gov Identifier
Research summary
Angelman syndrome is a neurogenetic disorder caused by a loss of function of the maternally inherited UBE3A gene. The gene is unique in that it is one of a small family of human imprinted genes. Angelman syndrome may affect areas of motor, language and cognitive functioning, seizures and ataxia combined with a characteristic presentation of a happy demeanour and sociability. It is a non degenerative, life-long disorder resulting in complete dependence on a caregiver that generally remains clinically unchanged with a normal life expectancy.
The purpose of this study is to determine if an investigational medicine called ION582, when given at different doses, is safe and tolerable. ION582 is a second-generation antisense oligonucleotide (ASO) drug targeted to UBE3A-ATS. It can increase the synthesis of UBE3A messenger ribonucleic acid (mRNA) and protein. Therefore, ION582 has the potential to halt, delay or reverse the progression of the underlying disease.
This is a Phase 1/2a, open-label, multiple ascending dose study conducted in multiple centres. Approximately 44 patients are planned to be enrolled in this study. The maximum total enrolment in the study will be 55 patients or until enrolment is closed by the Sponsor.
This study is composed of a 13-week Treatment Period with intrathecal bolus injections of ION582 and a 32-week Follow-up Period. Patients will be enrolled in 3 ascending dose levels in 5 cohorts to allow for the evaluation of treatment at different ION582 dose levels and age groups.
REC name
London - Brent Research Ethics Committee
REC reference
22/LO/0248
Date of REC Opinion
23 May 2022
REC opinion
Further Information Favourable Opinion