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) (ASPIRE-FTD)

April 7, 2026 updated by: AviadoBio Ltd

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)

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

18

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Belgium
  • Canada
    • Ontario
      • Toronto, Ontario, Canada
  • Italy
      • Milan, Italy
  • Netherlands
      • Amsterdam, Netherlands
        • Recruiting
        • Amsterdam UMC
  • Poland
  • Spain
      • Barcelona, Spain, 08036
      • Valencia, Spain, 46026
        • Recruiting
        • Hospital Universitari i Politecnic La Fe
  • Sweden
      • Lund, Sweden
        • Recruiting
        • Skåne University Hospital
        • Contact:
  • United Kingdom
      • Cambridge, United Kingdom, CB2 0QQ
      • Cardiff, United Kingdom, CF14 4XW
        • Recruiting
        • University Hospital of Wales
      • London, United Kingdom
        • Recruiting
        • University College London Hospitals
        • Contact:
  • United States
    • Ohio
      • Columbus, Ohio, United States, 43210
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Recruiting
        • Vanderbilt University Medical Centre
        • Contact:
    • Texas
      • Houston, Texas, United States, 77030

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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
  • 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 OR If, in the Investigator's opinion, the subject lacks capacity to consent, written informed consent of their legal representative must be obtained in accordance with local laws, regulations, and/or customs. In countries where local laws, regulations, and/or customs do not permit subjects who lack capacity to consent to participate in this study, these subjects will not be enrolled
  • 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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort 1 (dose 1)
Initial dose
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
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 3 (dose 3)
Additional dose
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 4 (dose 4)
Additional dose
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number and incidence of AEs and SAEs
Time Frame: Up to week 26
Type and incidence of adverse events
Up to week 26
Change from baseline in the Mini-Mental State Examination (MMSE)
Time Frame: 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.
Up to week 12
Incidence of treatment emergent suicidal ideation or behavior
Time Frame: 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.
26 week initial, 5-year total follow-up period
Incidence of treatment-emergent clinically significant abnormalities in clinical examination findings
Time Frame: 5-year total follow-up period
5-year total follow-up period
Incidence of treatment-emergent clinically significant abnormalities in safety laboratory values
Time Frame: 5-year total follow-up period
5-year total follow-up period
Change from baseline in brain structure
Time Frame: 5-year total follow-up period
Assessed by presence of any clinically significant MRI findings at post treatment visits including brain swelling or bleeding
5-year total follow-up period

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to achieve clearance of vector genomes
Time Frame: Up to week 26
Measured in plasma and semen (males only)
Up to week 26
Change from baseline in PGRN protein levels in CSF and blood
Time Frame: 26-week initial and 5-year total follow-up period
Change over time in level of PGRN
26-week initial and 5-year total follow-up period
Change from baseline in NfL levels in CSF and blood
Time Frame: 26-week initial and 5-year total follow-up period
Change over time in level of NfL
26-week initial and 5-year total follow-up period
Change from baseline in CDR + NACC FTLD-SB score
Time Frame: 5-year total follow-up period
The Clinical Dementia Staging Instrument (CDR) plus National Alzheimer's Coordinating Center Frontotemporal Degeneration domains (NACC FTLD) was developed as a way to improve characterization of cognitive and global function in patients with FTLD. The CDR+NACC FTLD score will capture patients' disease status. CDR+NACC FTLD Sum of Boxes (SB) score refers to the sum of the scores of each domain (sum of boxes) that ranges from 0 to 24.
5-year total follow-up period
Change from baseline in brain volumes
Time Frame: 5-year total follow-up period
Calculation based upon 3DT1 MRI scans
5-year total follow-up period
Change from baseline in AAV9 immunogenicity in blood
Time Frame: 5-year total follow-up period
Measured by level of antibodies and ELISPOT to AAV9 capsid
5-year total follow-up period
Change from baseline in AAV9 immunogenicity in CSF
Time Frame: 5-year total follow-up period
Measured by level of antibodies to AAV9 capsid
5-year total follow-up period
Change from baseline in PGRN immunogenicity in CSF
Time Frame: 5-year total follow-up period
Measured by level of antibodies to PGRN protein
5-year total follow-up period
Change from baseline in PGRN immunogenicity in blood
Time Frame: 5-year total follow-up period
Measured by level of antibodies and ELISPOT to PGRN protein
5-year total follow-up period
Change in Caregiver Global Impression of Change (CaGI-C)
Time Frame: 5-year total follow-up period
Global impression of change as assessed by the caregiver. The CaGI-C is a 7 point scale where 1= very much improved, 7= very much worse.
5-year total follow-up period
Change in Patient Global Impression of Change (PGI-C)
Time Frame: 5-year total follow-up period
Global impression of change as assessed by the patient. The PGI-C is a 7 point scale where 1= very much improved, 7= very much worse.
5-year total follow-up period
Change in Clinical Global Impression of Change (CGI-C)
Time Frame: 5-year total follow-up period
Global impression of change as assessed by the investigator (clinician). The CGI-C is a 7 point scale where 1= very much improved, 7= very much worse.
5-year total follow-up period
Change from baseline in GRN-specific Genetic Frontotemporal Initiative Cognitive (GENFI-Cog) composite score
Time Frame: 5-year total follow-up period

Calculated from the neuropsychological test battery that assesses various cognitive domains: language, attention/processing speed, executive function, verbal and visuospatial memory and social cognition.

Scores from the neuropsychological test battery are converted using standard statistical methods into the composite score. The GRN specific composite score is expected to be more sensitive to detect changes in cognition that are associated with FTD, and will be compared to the baseline score. Lower scores indicate worse performance.
5-year total follow-up period
Change from baseline in GFAP levels in CSF and blood
Time Frame: 5-year total follow-up period
Change over time in level of GFAP
5-year total follow-up period

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AviadoBio Ltd

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 30, 2023

Primary Completion (Estimated)

April 1, 2026

Study Completion (Estimated)

March 21, 2030

Study Registration Dates

First Submitted

September 12, 2023

First Submitted That Met QC Criteria

September 26, 2023

First Posted (Actual)

October 3, 2023

Study Record Updates

Last Update Posted (Actual)

April 13, 2026

Last Update Submitted That Met QC Criteria

April 7, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AVB-PGRN-001
  • 2023-509444-10-00 (Ctis)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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