A Phase 1/2 Open-Label, Ascending Dose, Multicenter Study to Evaluate the Safety and Preliminary Efficacy of AVB-101 Administered by Bilateral Intrathalamic Infusion in Subjects With Frontotemporal Dementia With Progranulin Mutations (FTD-GRN)

Frontotemporal dementia (FTD) is an early-onset form of dementia that typically presents with changes in behaviour, language, and motor function. There are currently no approved treatments for FTD. FTD with progranulin mutations (FTD-GRN) is caused by gene mutations in the human granulin (GRN) gene, which encodes for progranulin (PGRN), and accounts for 5-10% of all FTD cases. The pathophysiology of the disease is attributed to the deficiency of a single secreted protein, PGRN, meaning that FTD-GRN is particularly suited for a gene replacement approach, aiming to restore physiological levels of PGRN in broad areas of cortical tissue within the brain.The study drug, AVB-101 is a gene therapy medicinal product comprising a recombinant AAV9 vector encoding the human GRN gene. It is administered as a single dose intrathalamically (directly to the thalamus in the brain). It is anticipated that intrathalamic administration of AVB-101 has the potential to restore PGRN levels in patients with FTD-GRN, thereby slowing or stopping the progression of disease and preserving quality of life and overall survival.This is a Phase 1/2, open-label, multicentre, ascending dose, first-in-human study to evaluate the safety, tolerability, and preliminary efficacy of a single intrathalamic infusion of AVB-101 in subjects at risk for or with FTD-GRN. Approximately 9-15 eligible participants will be enrolled. Participants will receive a single dose of AVB-101 with the primary analysis occurring at 52 weeks post treatment. All participants receiving a dose of AVB-101 will be followed for 5 years. The total duration for participation is approximately 63 months (including screening and follow-up period). Participants will need the support of a caregiver/informant for the duration of the study.The study is sponsored by AviadoBio Ltd.