Phase1/2 with AT342 in patients with Crigler Najjar syndrome
Research type
Research Study
Full title
VALENS: A Phase 1/2, Randomized, Open-Label, Ascending-Dose, Delayed-Treatment Concurrent Control Clinical Study to Evaluate the Safety and Preliminary Efficacy of AT342, an AAV8-Delivered Gene Transfer Therapy in Crigler-Najjar Syndrome Subjects Aged 1 Year and Older
IRAS ID
226995
Contact name
Anil Dhawan
Contact email
Sponsor organisation
Audentes Therapeutics Inc.
Eudract number
2017-000876-27
Duration of Study in the UK
6 years, 7 months, 28 days
Research summary
Crigler-Najjar syndrome (CN) is an ultra-rare genetic disease characterised by a high level of unconjugated bilirubin (type of bilirubin toxic to brain) in patient’s blood. Unconjugated bilirubin is not eliminated properly because of a missing or defective gene called UGT1A1 leading to the lack of production of the UGT protein in the liver. UGT protein is necessary to breakdown and eliminate unconjugated bilirubin. Elevated bilirubin levels can lead to severe and irreversible neurological damage and death in newborns and early childhood. The disease management involves life-long daily phototherapy, usually for more than 10 hours a day. Although daily phototherapy reduces bilirubin levels in newborns, as the patient ages, phototherapy becomes less effective, and compliance is an issue due to its inconvenience and impact on quality of life.
To date, there is no authorised medicinal product for the treatment of CN syndrome.The only curative therapy for CN is liver transplantation requiring life-long immunosuppression treatment and there is risk of major complications related to surgery. This unmet medical need could be addressed by gene transfer therapy, such as with AT342.
The investigational drug AT342 has been developed to replace the missing or defective UGT1A1 gene. AT342 is an inactive virus that has been built to carry the UGT1A1 gene. AT342 could potentially produce new UGT protein in patients’ liver and reduce unconjugated bilirubin levels in the blood.
The purpose of this first in human study is to evaluate the safety of AT342 in CN patients, who receive prescribed daily phototherapy. The study will also determine the effectiveness of AT342 and the appropriate dose to be given to CN patients.
REC name
North East - York Research Ethics Committee
REC reference
17/NE/0210
Date of REC Opinion
8 Aug 2017
REC opinion
Further Information Favourable Opinion