Gene Therapy for Frontotemporal Dementia

(ASPIRE-FTD Trial)

Recruiting at 17 trial locations

Overseen By AviadoBio Clinical Trials

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: AviadoBio Ltd

Disqualifiers: Severe dementia, Other dementias, Stroke, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

9 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new gene therapy treatment called AVB-101 for individuals with Frontotemporal Dementia caused by a specific gene mutation. The study aims to determine if a one-time treatment with AVB-101 is safe, can restore normal protein levels in the brain, and possibly slow or stop symptoms. Participants will receive a single dose directly to the brain and will be monitored for five years. Suitable candidates include those diagnosed with Frontotemporal Dementia and possessing a related genetic mutation. As a Phase 1, Phase 2 trial, the study focuses on understanding how AVB-101 works in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to be among the first to benefit from this innovative treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have been treated with any investigational medicinal product within 60 days or 5 half-lives before the study, you may not be eligible to participate.

Is there any evidence suggesting that AVB-101 is likely to be safe for humans?

In a previous study, researchers examined the safety of AVB-101, a gene therapy for Frontotemporal Dementia with Progranulin Mutations (FTD-GRN). They monitored for any unwanted effects, known as adverse events, that might occur after treatment. As this study is in its early stages, safety is under close observation and review.

The treatment is administered once directly into the brain, and researchers aim to determine the optimal dose and assess patient tolerance. Early-stage studies like this primarily focus on ensuring the treatment's safety before evaluating its effectiveness. So far, no serious problems have been reported, but researchers continue to gather information to confirm AVB-101's long-term safety for patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for frontotemporal dementia, like cognitive enhancers and behavioral therapies, AVB-101 is a gene therapy that offers a unique approach. This therapy works by targeting the underlying genetic causes of the condition, potentially altering disease progression rather than just managing symptoms. Administered directly into the brain via an intrathalamic injection, AVB-101 delivers a one-time dose that could provide lasting effects, a significant departure from conventional treatments that require ongoing administration. Researchers are excited about this innovative mechanism and delivery method because it holds promise for more effective and long-lasting relief for patients.

What evidence suggests that AVB-101 might be an effective treatment for Frontotemporal Dementia?

Research shows that AVB-101 is designed to help with Frontotemporal Dementia with Progranulin Mutations (FTD-GRN) by increasing a protein called progranulin. Low levels of progranulin can cause brain cells to die, affecting brain function. Early findings suggest that AVB-101, when delivered directly to the brain, might restore progranulin levels. This trial will test AVB-101 in two different doses, delivered as a one-time intrathalamic administration. Initial studies indicate that AVB-101 is safe and might be effective, but further research is needed to confirm this. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults aged 30-75 with Frontotemporal Dementia (FTD) due to a specific genetic mutation (GRN). Participants must have certain symptoms, be able to consent, and have a study partner. They need enough thalamic volume in the brain and should commit to the study's procedures and schedule.

Inclusion Criteria

I am between 30 and 75 years old.

FTD as evidenced by CDR + NACC FTLD global score of 0.5, 1.0, or 2.0

A protocol defined minimum thalamic volume on each side on Screening MRI

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

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a one-time treatment of AVB-101 delivered directly to the brain

1 day

Initial Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of adverse events and suicidal ideation

26 weeks

Long-term Follow-up

Participants undergo follow-up assessments to monitor changes in cognitive function, brain structure, and immunogenicity

5 years

What Are the Treatments Tested in This Trial?

Interventions

• AVB-101

Trial Overview The trial tests AVB-101, a gene therapy delivered once directly into the brain. It aims to see if this treatment is safe for FTD-GRN patients, can restore normal protein levels associated with dementia, and potentially halt or slow disease progression.

How Is the Trial Designed?

Group I: Cohort 2 (dose 2) Experimental Treatment 2 Interventions

Escalated dose, delivered as a one-time only, intrathalamic administration.

Group II: Cohort 1 (dose 1) Experimental Treatment 2 Interventions

Initial dose, delivered as a one-time only, intrathalamic administration.

AVB-101 is already approved in United States, European Union for the following indications:

Approved in United States as AVB-101 for:

• Frontotemporal Dementia with Progranulin Mutations (FTD-GRN) - Investigational

Approved in European Union as AVB-101 for:

• Frontotemporal Dementia with Progranulin Mutations (FTD-GRN) - Investigational

Who Is Running the Clinical Trial?

AviadoBio Ltd

Lead Sponsor

Trials

1

Recruited

9+

Published Research Related to This Trial

Researchers created a human embryonic stem cell line with a CHMP2B mutation to model frontotemporal dementia (FTD), focusing on the role of astrocytes alongside neurons in disease progression.

The study found that astrocytes in FTD exhibit early alterations in their endolysosomal system and increased responsiveness to glutamate, which may lead to neuronal hyperactivity and synchronization, suggesting that astrocyte changes could trigger neuronal impairments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Astrocyte dysfunction and neuronal network hyperactivity in a CRISPR engineered pluripotent stem cell model of frontotemporal dementia. Canals, I., Comella-Bolla, A., Cepeda-Prado, E., et al.[2023]

Plasma levels of progranulin (PGRN) are significantly lower in individuals with granulin gene mutations compared to controls, indicating a potential biomarker for frontotemporal dementia (FTD).

Plasma PGRN levels are stable over a week, making them suitable for monitoring treatments aimed at increasing PGRN, but since they only moderately correlate with cerebrospinal fluid (CSF) PGRN levels, CSF sampling will still be necessary in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progranulin Levels in Plasma and Cerebrospinal Fluid in Granulin Mutation Carriers. Meeter, LH., Patzke, H., Loewen, G., et al.[2022]

Mutant CHMP2B, associated with frontotemporal dementia, disrupts endolysosomal trafficking in neurons, leading to impaired function and increased dendritic branching due to its inability to recruit the ATPase VPS4.

Treatment with antisense oligonucleotides targeting TMEM106B can restore endosomal health and improve trafficking in neurons, suggesting a promising therapeutic strategy for frontotemporal dementia linked to endolysosomal dysfunction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frontotemporal dementia causative CHMP2B impairs neuronal endolysosomal traffic-rescue by TMEM106B knockdown. Clayton, EL., Milioto, C., Muralidharan, B., et al.[2022]

Gene therapy using adeno-associated viral vectors to deliver the progranulin gene into the cerebrospinal fluid has shown promising results in mouse models and nonhuman primates, significantly increasing progranulin levels and normalizing markers of deficiency.

The AAV1 vector demonstrated superior efficacy in increasing progranulin expression compared to other variants, and the treatment was well tolerated with no significant toxicity, supporting its potential as a safe therapeutic option for frontotemporal dementia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adeno-associated virus serotype 1-based gene therapy for FTD caused by GRN mutations. Hinderer, C., Miller, R., Dyer, C., et al.[2021]

Frontotemporal degeneration (FTD) presents unique clinical and molecular features, such as rapid disease progression and distinct pathology, making it a promising target for developing effective therapies compared to other neurodegenerative disorders.

Recent consensus diagnostic criteria and sensitive assessment scales for FTD, along with insights from ongoing drug development in similar diseases, indicate that FTD research is now ready to advance towards clinical trials for specific treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The advantages of frontotemporal degeneration drug development (part 2 of frontotemporal degeneration: the next therapeutic frontier). Boxer, AL., Gold, M., Huey, E., et al.[2021]

Citations

1. aviadobio.com aviadobio.com/wp-content/uploads/2025/07/AAIC-2025-AVB-101-Clinical-Study-Update_FINAL_DIGITAL.pdf

A Phase 1/2 Clinical Study to Evaluate AVB-101 in FTD ... Data from this clinical trial are expected to inform further clinical development of AVB-101. RESULTS. Preliminary safety results from cohort 1 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06064890

A Study to Evaluate the Safety and Effect of AVB-101 ... 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 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11709883/

Pre‐clinical development of AVB‐101, an AAV gene ... AVB-101 is being developed as a one‐time treatment for FTD‐GRN administered bilaterally into the thalamus (ITM) by convection‐enhanced delivery using a ...

4. aviadobio.com aviadobio.com/wp-content/uploads/2024/09/ISFTD-2024_AVB-Trial-Design_DIGITAL_FINAL_04Sep2024-1.pdf

A Phase 1/2 Clinical Trial to Evaluate AVB-101 in FTD with ... ASPIRE-FTD is designed to evaluate the optimal dose, safety, tolerability and preliminary efficacy of AVB-101 in participants with FTD-GRN.

5. theaftd.org theaftd.org/posts/1ftd-in-the-news/b-ftd-grn-gene-therapy-abio/

First Participant Treated in AviadoBio Phase 1/2 Clinical ... AviadoBio announced on April 15 that the first participant has been treated in its trial evaluating the gene therapy AVB-101 for FTD-GRN.

6. progranulinnavigator.org progranulinnavigator.org/trials/a-study-to-evaluate-the-safety-and-effect-of-avb-101-a-gene-therapy-product-in-subjects-with-a-genetic-subtype-of-frontotemporal-dementia-ftd-grn-aspire-ftd

A Study to Evaluate the Safety and Effect of AVB-101 ... The study will collect data to evaluate how safe AVB-101 is, as well as whether AVB-101 restores normal progranulin protein levels in the brain. Investigators ...