Gene Therapy with GNT0003 for Severe Crigler-Najjar Syndrome

This study is focused on finding a new treatment for adults with severe Crigler-Najjar Syndrome (CNS), a very rare genetic disorder that causes a buildup of a harmful substance called bilirubin in the body. People with severe CNS often need daily light therapy to manage their condition because there is currently no medical cure available, with liver transplantation being the only option for a permanent solution. The study explores the use of a new gene therapy treatment called GNT0003, which aims to correct the genetic problem causing CNS. This is particularly important for patients who have existing antibodies that typically prevent them from receiving such gene therapies. Participants in the study will receive a single intravenous dose of GNT0003, but first, they will be treated with a drug called imlifidase to help reduce the antibodies that might interfere with the gene therapy. The study will be conducted in three parts: an initial period to understand each participant's condition, a treatment phase, and a long-term follow-up lasting several years. Researchers will closely monitor participants to evaluate how effectively the treatment reduces bilirubin levels, as well as its safety and any side effects. Additionally, the study will gather information on participants' quality of life and how the treatment affects their overall health over time.