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)

Purpose

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.

Conditions

  • Frontotemporal Dementia
  • FTD
  • FTD-GRN
  • Dementia, Frontotemporal

Eligibility

Eligible Ages
Between 30 Years and 75 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Male or female, 30 to 75 years of age - Carriers of a pathogenic GRN mutation - FTD as evidenced by CDR + NACC FTLD global score of 0.5, 1.0, or 2.0 - Presence of 1 or more of the criteria for diagnosis of possible bvFTD or PPA - A protocol defined minimum thalamic volume on each side on Screening MRI - Able and willing to comply with all procedures and the study visit schedule - Able and willing to give written informed consent prior to study participation, and agree to designate a legal representative to act on their wishes to continue participation should they lose capacity to consent at some point during the study - An identified, informed study partner who is able and willing to support the participant in the study and to provide assessments of the participant during the study

Exclusion Criteria

  • Severe dementia, defined as CDR + NACC FTLD global score of 3.0, or other symptoms that preclude the ability to comply with study procedures and/or pose unacceptable safety risk to the subject - Any concurrent disease that may cause cognitive impairment unrelated to mutations in the GRN gene, such as other causes of dementia, neurosyphilis, hydrocephalus, stroke, small vessel ischemic disease, uncontrolled hypothyroidism, or vitamin B12 deficiency - Clinically significant abnormality on MRI at Screening considered to be a contraindication to Intrathalamic infusion - Surgically significant pattern of brain atrophy on MRI at Screening that interferes with planned neurosurgical trajectory - Previous treatment with any gene or cell therapy - Previous treatment with any investigational medicinal product (IMP) within 60 days or 5 half-lives (whichever is longer) prior to study drug treatment - Concomitant disease, any clinically significant laboratory abnormality, or treatment which, in the opinion of the Investigator, may pose an unacceptable safety risk to the participant or interfere with study conduct or the participant's ability to comply with study procedures including neurosurgical administration under anesthesia

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Cohort 1 (dose 1) 		Initial dose, delivered as a one-time only, intrathalamic administration.
  • Procedure: Intrathalamic AAV.PGRN administration
    One-time MRI-guided stereotaxic infusion of AAV.PGRN into the brain
  • Genetic: 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.
Experimental
Cohort 2 (dose 2) 		Escalated dose, delivered as a one-time only, intrathalamic administration.
  • Procedure: Intrathalamic AAV.PGRN administration
    One-time MRI-guided stereotaxic infusion of AAV.PGRN into the brain
  • Genetic: 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.

Recruiting Locations

Vanderbilt University Medical Centre
Nashville, Tennessee 37232
Contact:
Jerica Reeder
615-875-2987
jerica.reeder@vumc.org

More Details

Status
Recruiting
Sponsor
AviadoBio Ltd

Study Contact

AviadoBio Clinical Trials
+44 203-089-7917
clinicaltrials@aviadobio.com

For general questions about clinical trials, contact Research Support Services at (615) 322-7343 or research.support.services@vumc.org