Evaluating the safety and effect of AVB-101 gene therapy in participants with frontotemporal dementia with progranulin mutations

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

Study Summary

This study looks at whether a single treatment of AVB-101 gene therapy delivered to the brain is safe and if it can improve symptoms in people living with frontotemporal dementia.

What is the study about?

This study is looking at a gene therapy called AVB-101 to see if it can help treat a disease called Frontotemporal Dementia with Progranulin Mutations (FTD-GRN). FTD-GRN is a type of dementia that usually starts at a younger age and can affect a person’s behavior, language, and movement. These symptoms can happen when there is not enough of a protein called progranulin (PGRN) in the brain, which can lead to the brain not working properly.

Participants will receive a one-time dose of AVB-101 during a surgery at a hospital in Ohio, USA that specializes in brain surgery. After the surgery, participants will be carefully observed and followed for five years at Sunnybrook Health Sciences in Toronto. The study will look at how safe AVB-101 is for people living with FTD-GRN. It will also help us understand if AVB-101 works as treatment to slow down or stop progression of FTD-GRN.

Eligibility – Who can participate?

• Between 30-75 years of age
• Diagnosed with frontotemporal dementia (FTD)
• Have genetic test results confirming a mutation in the GRN gene encoding progranulin (GRN)
• Have someone who is able and willing to support the participant in the study and accompany you to the study visits
• Not have had previous treatment with any gene or cell therapy

Time requirement

The study will last about 5 years and 3 months, with 19 visits to study sites.

Screening & Baseline Testing:

• This will happen over 2 different visits to Sunnybrook, each visit may occur over 1-2 days.
• Visits will last about 6 hours each and will involve collecting your medical history, blood, vital signs (blood pressure, heart rate, temperature, and breathing rate), MRI brain scans, cognitive testing, lumbar puncture to collect cerebrospinal fluid, electrocardiogram, and neurological and physical exam.

Treatment (Surgery):

• A few days prior to surgery, the participant will attend the neurosurgery hospital for further standard tests which will take about 8 hours
• The surgery to deliver AVB-101 will take 8-10 hours at the neurosurgery hospital.
• You will receive general anesthesia, so you will be unconscious and unaware of the procedure taking place.

Post-surgery Hospital Stay:

• After surgery, the participant will stay at the hospital for 1-2 days for monitoring.
• The participant may need to stay in nearby accommodation for up to 1 week.

Follow-up Visits:

• The participant will have follow-up visits at Sunnybrook for 5 years.
• In the first year, visits will be frequent and will involve repeating the same assessments as the baseline testing visits.
• After the first year, visits will happen every 6 months to check on the participant’s progress.

TDRA study investigator

Dr. Mario Masellis

More information

https://clinicaltrials.gov/study/NCT06064890

TDRA Site:

Sunnybrook Health Sciences Centre,

Address: 2075 Bayview Ave, Toronto, ON M4N 3M5

Target Population:

Frontotemporal dementia (FTD)