A Study to Evaluate the Safety and Effect of AVB-101, a Gene Therapy Product, in Subjects With a Genetic Sub-type of Frontotemporal Dementia (FTD-GRN)

Condition(s) studied

Investigational drug(s) / intervention(s)

Intrathalamic AAV.PGRN administration: One-time MRI-guided stereotaxic infusion of AAV.PGRN into the brain

Intrathalamic AVB-101: AVB-101 is made from an adeno-associated virus, serotype 9 (AAV9). AAVs are small viruses that are naturally occurring and do not cause illness or infection on their own. AVB-101 has been modified to contain a copy of the correct (non-mutated) GRN gene, plus some other genetic material to enable the GRN gene to function inside neurons (cells within the brain). AVB-101 has also been modified so that it cannot divide and make new copies of itself (known as 'replication'), which means that it cannot cause disease or a large immune response in your body.

Study summary

The goal of this clinical study is to learn about an investigational gene therapy product called AVB-101, which is designed to treat a disease called Frontotemporal Dementia with Progranulin Mutations (FTD-GRN). FTD-GRN is an early-onset form of dementia, a progressive brain disorder that affects behavior, language and movement. These symptoms result from below normal levels of a protein called progranulin (PGRN) in the brain, which leads to the death of nerve cells (neurons), affecting the brain's ability to function.

The main questions that the study aims to answer are:

1. Is a one-time treatment with AVB-101 safe for patients with FTD-GRN?
2. Does a one-time treatment with AVB-101 restore PGRN levels to at least normal levels?
3. Could AVB-101 work as a treatment to slow down or stop progression of FTD-GRN?

In this study there is no placebo (a dummy pill or treatment used for comparison purposes), so all participants will receive a one-time treatment of AVB-101 delivered directly to the brain, with follow-up assessments for 5 years.

Eligibility

Primary outcome measure(s)

• Number and incidence of AEs and SAEs — Up to week 26
  Type and incidence of adverse events
• Change from baseline in the Mini-Mental State Examination (MMSE) — Up to week 12
  Mini-Mental State Examination (MMSE) is a global assessment of cognitive status. Score range 0-30; higher scores reflect better cognitive function. Change in MMSE score from baseline visit to post-treatment visit will be assessed.
• Incidence of treatment emergent suicidal ideation or behavior — 26 week initial, 5-year total follow-up period
  The Columbia-Suicide Severity Rating Scale (C-SSRS) is an assessment tool that evaluates suicidal ideation and behavior. C-SSRS will be measured at each visit to assess for absence/presence of suicidal ideation and/or behavior.
• Incidence of treatment-emergent clinically significant abnormalities in clinical examination findings — 5-year total follow-up period
• Incidence of treatment-emergent clinically significant abnormalities in safety laboratory values — 5-year total follow-up period
• Change from baseline in brain structure — 5-year total follow-up period
  Assessed by presence of any clinically significant MRI findings at post treatment visits including brain swelling or bleeding

Trial sites (19)