Anti-VEGF Gene Therapy for Acoustic Neuroma

Recruiting at 3 trial locations

Overseen By Akouos Clinical Trials

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Akouos, Inc.

Disqualifiers: NF2, Bilateral vestibular schwannoma, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

27 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new gene therapy, AAVAnc80-antiVEGF, for individuals with a growing benign tumor called vestibular schwannoma, which can affect hearing. Researchers seek to determine if the therapy is safe and tolerable when delivered directly into the ear using a special device. Participants will receive one of three doses to identify the most effective treatment. Individuals with a single-sided vestibular schwannoma larger than 2 mm and severe hearing loss in that ear may be suitable candidates for this trial. As a Phase 1 trial, participants will be among the first to receive this innovative treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments and delivery device are likely to be safe?

Research shows that treatments like AAVAnc80-antiVEGF have been studied for their ability to improve nerve function in animals. These studies suggest that the treatment can help by reducing nerve problems. Although specific safety data for humans is not yet available, this trial phase provides some insights. Early trials primarily focus on assessing safety. If a treatment is in this phase, it has passed basic safety tests in labs and with animals.

The trial for AAVAnc80-antiVEGF aims to evaluate how well people tolerate different doses. So far, trials with similar treatments have reported no serious side effects. This trial will closely monitor for any possible side effects. Participants receive a single dose, which may help lower potential risks. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for acoustic neuroma, which often involve surgery or radiation, AAVAnc80-antiVEGF is a gene therapy that uses an innovative approach. This therapy targets the vascular endothelial growth factor (VEGF), aiming to reduce the growth of the tumor by cutting off its blood supply. Researchers are excited because this method could potentially treat the condition with a single administration, reducing the need for invasive procedures. Additionally, the use of a viral vector, AAVAnc80, allows for precise delivery of the therapy directly into the cochlea, which might lead to more effective outcomes with fewer side effects.

What evidence suggests that this trial's treatments could be effective for acoustic neuroma?

Research has shown that anti-VEGF gene therapy might be a promising treatment for acoustic neuroma. Anti-VEGF blocks a protein that helps tumors grow new blood vessels, potentially slowing or stopping tumor growth. In animal studies, anti-VEGF therapy improved nerve function by reducing nerve damage. Early research suggests it may help with hearing loss related to vestibular schwannoma (another term for acoustic neuroma). In this trial, participants will receive a single unilateral intracochlear administration of AAVAnc80-antiVEGF at different dose levels, and the results so far appear hopeful. ^{1 3 4 5 6}

Who Is on the Research Team?

Kathy Reape, MD

Principal Investigator

Akouos, Inc.

Are You a Good Fit for This Trial?

This trial is for individuals with vestibular schwannoma, also known as acoustic neuroma. Participants must meet certain health criteria to be eligible, but specific inclusion and exclusion details are not provided.

Inclusion Criteria

Able and willing to comply with all trial requirements, including willingness to participate in a separate long term follow-up study after completion of this trial

I have a growing tumor on my balance nerve in one ear.

Profound hearing loss, defined by pure-tone audiometry thresholds or word recognition score, in the affected ear

Exclusion Criteria

I have been diagnosed with NF2 or have tumors on both hearing nerves.

Prior participation in a clinical trial with an investigational drug within six months prior to administration (Day 0), or any prior participation in a gene therapy clinical trial

I have had surgery or radiation for a brain tumor on my hearing nerve.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single unilateral intracochlear administration of AAVAnc80-antiVEGF using a sterile, one-time use investigational medical device

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including changes in tumor size and frequency of adverse events

approximately one year

What Are the Treatments Tested in This Trial?

Interventions

• AAVAnc80-antiVEGF

Trial Overview The study tests the safety of a gene therapy called AAVAnc80-antiVEGF delivered through the Akouos device. It will assess three different dose levels administered once unilaterally (to one ear).

How Is the Trial Designed?

Group I: Cohort 3 Experimental Treatment 1 Intervention

Adult participants to receive a single unilateral intracochlear administration of AAVAnc80-antiVEGF (dose level 3) in the study ear using a sterile, one-time use investigational medical device

Group II: Cohort 2 Experimental Treatment 1 Intervention

Adult participants to receive a single unilateral intracochlear administration of AAVAnc80-antiVEGF (dose level 2) in the study ear using a sterile, one-time use investigational medical device.

Group III: Cohort 1 Experimental Treatment 1 Intervention

Adult participants to receive a single unilateral intracochlear administration of AAVAnc80-antiVEGF (dose level 1) in the study ear using a sterile, one-time use investigational medical device.

Who Is Running the Clinical Trial?

Akouos, Inc.

Lead Sponsor

Trials

4

Recruited

220+

Eli Lilly and Company

Industry Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Published Research Related to This Trial

In a study of 7 pediatric patients with neurofibromatosis type 2 (NF2) receiving bevacizumab for progressive vestibular schwannomas, the treatment resulted in a significant reduction in tumor growth rate, from 138% annually before treatment to 36% after one year.

Bevacizumab was well tolerated and led to one instance of hearing improvement, suggesting it could be a promising option for managing vestibular schwannomas in children, especially if initiated early in the treatment process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab decreases vestibular schwannomas growth rate in children and teenagers with neurofibromatosis type 2. Hochart, A., Gaillard, V., Baroncini, M., et al.[2022]

In a study of 12 patients with rapidly growing vestibular schwannomas treated with bevacizumab, certain MRI-derived parameters were found to predict tumor response, with larger tumors showing better responses to treatment.

Key predictive biomarkers included lower relaxation rate (R1(N)) and higher contrast transfer coefficient (K(trans)), indicating that these MRI metrics can help assess the effectiveness of antiangiogenic therapy in managing vestibular schwannomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vascular biomarkers derived from dynamic contrast-enhanced MRI predict response of vestibular schwannoma to antiangiogenic therapy in type 2 neurofibromatosis. Li, KL., Djoukhadar, I., Zhu, X., et al.[2018]

Bevacizumab treatment in a 40-year-old woman with Neurofibromatosis type 2 (NF2) led to significant improvements in hearing and a reduction in tumor volume after 6 months, demonstrating its efficacy in managing this condition.

The patient experienced no adverse events during treatment, indicating that bevacizumab is a safe option for NF2 patients who are not suitable for surgery or radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab treatment for vestibular schwannoma in a patient with neurofibromatosis type 2: hearing improvement and tumor shrinkage. Sponghini, AP., Platini, F., Rondonotti, D., et al.[2017]

The anti-VEGF agent bevacizumab has shown therapeutic efficacy in treating vestibular schwannomas, leading to tumor size reduction and improved hearing in patients with neurofibromatosis type 2, indicating its potential as a treatment option.

VEGF plays a significant role in various hearing loss conditions, including otitis media with effusion and sensorineural hearing loss, with studies showing that VEGF receptor inhibitors can improve hearing in animal models and that recombinant VEGF can reproduce clinical findings in otitis media.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of vascular endothelial growth factor and vascular stability in diseases of the ear. London, NR., Gurgel, RK.[2014]

In a study of 22 patients with neurofibromatosis type 2 (NF2), high-dose bevacizumab (10 mg/kg every 2 weeks) resulted in a hearing response in 41% of participants after 6 months, which is similar to the 35%-40% response seen with standard doses.

Despite the high-dose treatment, there was no significant improvement in tumor shrinkage for pediatric patients, and the treatment did not lead to a decrease in free vascular endothelial growth factor, suggesting that alternative strategies may be needed for children with NF2.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter, Prospective, Phase II and Biomarker Study of High-Dose Bevacizumab as Induction Therapy in Patients With Neurofibromatosis Type 2 and Progressive Vestibular Schwannoma. Plotkin, SR., Duda, DG., Muzikansky, A., et al.[2020]

Bevacizumab, an anti-VEGF therapy, significantly reduced tumor growth and improved survival rates in animal models of schwannomas, with a 50% decrease in tumor growth rate and at least a 50% extension in survival for mice with intracranial schwannomas.

The treatment normalized the blood vessel structure and function in the tumors, leading to increased tumor necrosis and apoptosis, suggesting that it works by restoring a balance between VEGF and semaphorin 3 signaling.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-vascular endothelial growth factor therapies as a novel therapeutic approach to treating neurofibromatosis-related tumors. Wong, HK., Lahdenranta, J., Kamoun, WS., et al.[2022]

In a study of 17 patients with sporadic vestibular schwannomas, both vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were found to be expressed at the mRNA and protein levels in all tumor samples, indicating their potential role in tumor biology.

The expression levels of bFGF and VEGF were positively correlated with tumor volume, growth index, and microvessel density, suggesting that these factors may influence the growth characteristics of vestibular schwannomas through angiogenic and neurotrophic mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expression of vascular endothelial growth factor and basic fibroblast growth factor in sporadic vestibular schwannomas correlates to growth characteristics. Koutsimpelas, D., Stripf, T., Heinrich, UR., et al.[2017]

Bevacizumab shows potential in controlling vestibular schwannoma (VS) growth in patients with neurofibromatosis type 2 (NF2), with 41% of patients experiencing partial tumor regression and 20% showing hearing improvement after treatment.

However, serious side effects were noted in 17% of patients, indicating that while bevacizumab can be effective, its use should be carefully considered due to the risk of adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of bevacizumab for vestibular schwannoma in neurofibromatosis type 2: a systematic review and meta-analysis of treatment outcomes. Lu, VM., Ravindran, K., Graffeo, CS., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06517888

Anti-VEGF Gene Therapy Trial for Vestibular Schwannoma A Phase 1/2 Trial of AAVAnc80-antiVEGF Gene Therapy in Individuals With Unilateral Vestibular Schwannoma ... Vestibular schwannoma. Hearing loss. Acoustic neuroma.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4664377/

Anti-VEGF treatment improves neurological function and ... We modeled the effect anti-VEGF therapy on neurological function in the sciatic nerve model and found that it improves neurological function by alleviating ...

3. withpower.com withpower.com/trial/phase-2-neurilemmoma-8-2024-90d01

Anti-VEGF Gene Therapy for Acoustic Neuroma This Phase 1 & 2 medical study run by Akouos, Inc. is evaluating whether AAVAnc80-antiVEGF will have tolerable side effects & efficacy for patients with ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06517888?term=vestibular&cond=Neuroma,%20Acoustic&aggFilters=status:not%20rec%20enr%20act,ages:adult%20older&start=2016-01-01_&viewType=Table&rank=9

Anti-VEGF Gene Therapy Trial for Vestibular Schwannoma An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

5. mayo.edu mayo.edu/research/clinical-trials/diseases-conditions/acoustic-neuroma

Acoustic Neuroma Clinical Trials The primary objective of this study is to compare long-term quality of life outcomes between treatments for sporadic acoustic neuromas. Anti-VEGF Gene Therapy ...

6. careacross.com careacross.com/clinical-trials/trial/NCT06517888

Anti-VEGF Gene Therapy Trial for Vestibular Schwannoma This trial will evaluate the safety and tolerability of a single unilateral administration of one of three dose levels of AAVAnc80-antiVEGF.