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)

NCT06064890 | Recruiting Phase 1 DMC FDA Device

• 2 other identifiers: AVB-PGRN-0012023-509444-10-00
• Study Type: interventional
• Target: 18
• Locations: 9 countries
• Sites: 19

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

Conditions

Frontotemporal Dementia; FTD; FTD-GRN; Dementia, Frontotemporal

Keywords

Gene Therapy; AAV; Intrathalamic; Intraparenchymal; Progranulin; Behavioral Variant FTD; Primary Progressive Aphasia; PGRN; Granulin; Dementia; Dementia Gene Therapy; AAV9

Outcome Measures

Primary Outcomes (6)

• Number and incidence of AEs and SAEs

  Type and incidence of adverse events

  Up to week 26

• Change from baseline in the Mini-Mental State Examination (MMSE)

  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

  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

  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

  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 Outcomes (14)

• Change from baseline in PGRN protein levels in CSF and blood

  26-week initial and 5-year total follow-up period

• Change from baseline in NfL levels in CSF and blood

  26-week initial and 5-year total follow-up period

• Change from baseline in CDR + NACC FTLD-SB score

  5-year total follow-up period

• Time to achieve clearance of vector genomes

  Up to week 26

• Change from baseline in brain volumes

  5-year total follow-up period

Study Arms (4)

Cohort 1 (dose 1)

EXPERIMENTAL

Initial dose

Procedure: Intrathalamic AAV.PGRN administration; Genetic: Intrathalamic AVB-101

Cohort 2 (dose 2)

EXPERIMENTAL

Escalated dose

Procedure: Intrathalamic AAV.PGRN administration; Genetic: Intrathalamic AVB-101

Cohort 3 (dose 3)

EXPERIMENTAL

Additional dose

Procedure: Intrathalamic AAV.PGRN administration; Genetic: Intrathalamic AVB-101

Cohort 4 (dose 4)

EXPERIMENTAL

Additional dose

Procedure: Intrathalamic AAV.PGRN administration; Genetic: Intrathalamic AVB-101

Interventions

Intrathalamic AAV.PGRN administration PROCEDURE

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

Cohort 1 (dose 1); Cohort 2 (dose 2); Cohort 3 (dose 3); Cohort 4 (dose 4)

Intrathalamic AVB-101 GENETIC

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.

Cohort 1 (dose 1); Cohort 2 (dose 2); Cohort 3 (dose 3); Cohort 4 (dose 4)

Eligibility Criteria

• Age: 30 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AviadoBio Ltd: lead

Study Sites (19)

The Ohio State University (OSU) Wexner Medical Center

Columbus, Ohio, 43210, United States

RECRUITING

Vanderbilt University Medical Centre

Nashville, Tennessee, 37232, United States

RECRUITING

Houston Methodist Hospital

Houston, Texas, 77030, United States

RECRUITING

UZ Leuven

Leuven, Belgium

RECRUITING

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

RECRUITING

Fondazione IRCCS Istituto Neurologico Carlo Besta

Milan, Italy

RECRUITING

Amsterdam UMC

Amsterdam, Netherlands

RECRUITING

NEURO-CARE Sp. z o.o. Sp. Komandytowa

Katowice, Poland

RECRUITING

Neurologia Slaska Centrum Medyczne

Katowice, Poland

RECRUITING

Uniwersyteckie Centrum Kliniczne, SUM w Katowicach

Katowice, Poland

RECRUITING

Euromedis Sp. z o.o.

Szczecin, 70-111, Poland

RECRUITING

Centrum Medyczne NeuroProtect Sp z o.o.

Warsaw, Poland

RECRUITING

Mazowiecki Szpital Brodnowski Sp. z o. o.

Warsaw, Poland

RECRUITING

Hospital Clinic Barcelona

Barcelona, 08036, Spain

RECRUITING

Hospital Universitari i Politecnic La Fe

Valencia, 46026, Spain

RECRUITING

Skåne University Hospital

Lund, Sweden

RECRUITING

Cambridge University Hospitals NHS Foundation Trust

Cambridge, CB2 0QQ, United Kingdom

RECRUITING

University Hospital of Wales

Cardiff, CF14 4XW, United Kingdom

RECRUITING

University College London Hospitals

London, United Kingdom

RECRUITING

MeSH Terms

Conditions

Frontotemporal Dementia; Aphasia, Primary Progressive; Dementia

Condition Hierarchy (Ancestors)

Frontotemporal Lobar Degeneration; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; TDP-43 Proteinopathies; Neurodegenerative Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Neurocognitive Disorders; Mental Disorders; Aphasia; Speech Disorders; Language Disorders; Communication Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Central Study Contacts

AviadoBio Clinical Trials

CONTACT

+44 203-089-7917; clinicaltrials@aviadobio.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2023
• First Posted: October 3, 2023
• Study Start: August 30, 2023
• Primary Completion: April 1, 2026
• Study Completion (Estimated): March 21, 2030
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1); NL (1); US (3); BE (1); SE (1); CA (1); ES (2); GB (3); PL (6)