Anti-VEGF Gene Therapy for Acoustic Neuroma
Palo Alto (17 mi)Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Akouos, Inc.
No Placebo Group
Trial Summary
What is the purpose of this trial?This trial will evaluate the safety and tolerability of a single unilateral administration of one of three dose levels of AAVAnc80-antiVEGF and will evaluate the Akouos delivery device to safely achieve the intended product performance.
What data supports the idea that Anti-VEGF Gene Therapy for Acoustic Neuroma is an effective treatment?The available research shows that Anti-VEGF treatments, like bevacizumab, can effectively control tumor growth and improve hearing in patients with neurofibromatosis type 2 (NF2), which is similar to acoustic neuroma. In one study, the tumor growth rate decreased by an average of 50% in animal models, and survival was extended by at least 50%. Another study on children and teenagers with NF2 showed a significant reduction in tumor growth rate after one year of treatment, and some patients experienced hearing improvement. These results suggest that Anti-VEGF treatments can be effective in managing tumor growth and preserving hearing, making them a promising option compared to traditional surgery, which can have more severe side effects.127910
Is the treatment AAVAnc80-antiVEGF a promising treatment for acoustic neuroma?Yes, AAVAnc80-antiVEGF is a promising treatment for acoustic neuroma because it targets VEGF, which is important for tumor growth. Similar treatments, like bevacizumab, have shown success in reducing tumor size and improving hearing in patients with related conditions.2481011
What safety data exists for Anti-VEGF Gene Therapy for Acoustic Neuroma?The provided research does not contain any safety data for Anti-VEGF Gene Therapy for Acoustic Neuroma or related treatments like AAVAnc80-antiVEGF. The studies focus on the safety and efficacy of aprepitant for nausea and vomiting, unrelated to the gene therapy in question.3561213
Do I need to stop my current medications to join the trial?The trial protocol does not specify whether you need to stop taking your current medications.
Eligibility Criteria
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
I have a growing tumor on my balance nerve in one ear.
My vestibular schwannoma is larger than 2 mm.
Exclusion Criteria
I have been diagnosed with NF2 or have tumors on both hearing nerves.
I have had surgery or radiation for a brain tumor on my hearing nerve.
I have experienced fluctuating hearing loss or sudden dizziness.
Treatment Details
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).
3Treatment groups
Experimental Treatment
Group I: Cohort 3Experimental Treatment1 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 2Experimental Treatment1 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 1Experimental Treatment1 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.
Find a clinic near you
Research locations nearbySelect from list below to view details:
Mayo ClinicRochester, MN
University of Texas SouthwesternDallas, TX
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Who is running the clinical trial?
Akouos, Inc.Lead Sponsor
Eli Lilly and CompanyIndustry Sponsor
References
Expression of vascular endothelial growth factor and basic fibroblast growth factor in sporadic vestibular schwannomas correlates to growth characteristics. [2017]Expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) may have an impact on the growth characteristics of sporadic vestibular schwannomas (VSs).
Anti-vascular endothelial growth factor therapies as a novel therapeutic approach to treating neurofibromatosis-related tumors. [2022]Patients with bilateral vestibular schwannomas associated with neurofibromatosis type 2 (NF2) experience significant morbidity such as complete hearing loss. We have recently shown that treatment with bevacizumab provided tumor stabilization and hearing recovery in a subset of NF2 patients with progressive disease. In the current study, we used two animal models to identify the mechanism of action of anti-vascular endothelial growth factor (VEGF) therapy in schwannomas. The human HEI193 and murine Nf2(-/-) cell lines were implanted between the pia and arachnoid meninges as well as in the sciatic nerve to mimic central and peripheral schwannomas. Mice were treated with bevacizumab (10 mg/kg/wk i.v.) or vandetanib (50 mg/kg/d orally) to block the VEGF pathway. Using intravital and confocal microscopy, together with whole-body imaging, we measured tumor growth delay, survival rate, as well as blood vessel structure and function at regular intervals. In both models, tumor vessel diameter, length/surface area density, and permeability were significantly reduced after treatment. After 2 weeks of treatment, necrosis in HEI193 tumors and apoptosis in Nf2(-/-) tumors were significantly increased, and the tumor growth rate decreased by an average of 50%. The survival of mice bearing intracranial schwannomas was extended by at least 50%. This study shows that anti-VEGF therapy normalizes the vasculature of schwannoma xenografts in nude mice and successfully controls the tumor growth, probably by reestablishing a natural balance between VEGF and semaphorin 3 signaling.
[A meta-analysis of aprepitant for prevention of chemotherapy-induced nausea and vomiting]. [2018]To assess the efficacy and safety of aprepitant for the prevention of chemotherapy-induced nausea and vomiting (CINV) after moderately or highly emetogenic chemotherapy.
The role of vascular endothelial growth factor and vascular stability in diseases of the ear. [2014]Vascular endothelial growth factor (VEGF) is a critical mediator of vascular permeability and angiogenesis and likely plays an important role in cochlear function and hearing. This review highlights the role of VEGF in hearing loss associated with vestibular schwannomas, otitis media with effusion, and sensorineural hearing loss.
Aprepitant and granisetron for the prophylaxis of radiotherapy-induced nausea and vomiting after moderately emetogenic radiotherapy for bone metastases: a prospective pilot study. [2022]We evaluated the novel combination of aprepitant and granisetron for the prophylaxis of radiotherapy-induced nausea and vomiting (rinv) among patients receiving moderately-emetogenic radiotherapy for thoracolumbar bone metastases.
Aprepitant for the prevention of chemotherapy-induced nausea and vomiting in children: a randomised, double-blind, phase 3 trial. [2018]Oral aprepitant, a neurokinin-1 receptor antagonist, is recommended in combination with other anti-emetic agents for the prevention of nausea and vomiting associated with moderately or highly emetogenic chemotherapy in adults, but its efficacy and safety in paediatric patients are unknown. We did this phase 3 trial to examine the safety and efficacy of such treatment in children.
Bevacizumab decreases vestibular schwannomas growth rate in children and teenagers with neurofibromatosis type 2. [2022]Vestibular schwannoma (VS) growth in neurofibromatosis type 2 (NF2) can be responsible for brainstem compression and hearing loss. Surgical removal remains the standard therapy despite potential morbidity. Previous studies suggested that the inhibition of the VEGF-pathway with bevacizumab could result in hearing improvement, reduction of the tumor volume or both in adults. We retrospectively describe the French experience of bevacizumab treatment delivered for progressive VS in pediatric NF2 patients. Patients received Bevacizumab 5 or 10 mg/kg every 2 weeks according to the physician's choice. Follow-up included clinical assessment, audiometry and volumetric MRI every 3-6 months. Seven patients harboring 11 VS were included. The median age at inclusion was 15 years (11.4-18.8), and the median treatment duration was 11.3 months (3.2-55.6). At baseline, the median tumor volume was 1.2 cm(3) (0.52-13.5) and the median word recognition score was 90 % (0-100). We observed one major response, two minor responses and a decrease in the rate of tumor growth for the 4 other patients. The median annual growth rate before treatment was significantly higher than after 1 year of treatment (138 vs. 36 %, n = 5, p = 0.043). We noted one hearing improvement over the course of 1 year under treatment (hearing response rate was 14 %). Overall, the treatment was well tolerated. Our study supports that bevacizumab is an attractive therapeutic option for pediatric NF2 patients with growing VS. Thorough multidisciplinary evaluation is necessary to identify the best candidates prior to treatment. It is likely that a better functional outcome would be expected if targeted therapies were discussed early in the management of the disease.
Bevacizumab treatment for vestibular schwannoma in a patient with neurofibromatosis type 2: hearing improvement and tumor shrinkage. [2017]Neurofibromatosis type 2 (NF2) is a dominantly inherited genetic condition that clinically manifests through the appearance of multiple meningiomas, ependymomas and bilateral vestibular schwannomas (acoustic neuromas) which lead to progressive hearing loss. Neovascularization is necessary for tumor growth and is driven by tumor-produced angiogenic factors such as vascular endothelial growth factor (VEGF). Bevacizumab is a humanized monoclonal antibody that neutralizes the activity of VEGF. Recent data have shown that VEGF is produced by schwannoma tumor cells. Bevacizumab treatment in patients with NF2 who were considered poor candidates for surgery and radiation therapy was found to result in clinically meaningful hearing improvement and tumor volume reduction in previous studies.
Vascular biomarkers derived from dynamic contrast-enhanced MRI predict response of vestibular schwannoma to antiangiogenic therapy in type 2 neurofibromatosis. [2018]Antiangiogenic therapy of vestibular schwannoma (VS) in type 2 neurofibromatosis can produce tumor shrinkage with response rates of 40%-60%. This study examines the predictive value of parameter-derived MRI in this setting.
Efficacy and safety of bevacizumab for vestibular schwannoma in neurofibromatosis type 2: a systematic review and meta-analysis of treatment outcomes. [2020]Individual evidence suggests that the anti-angiogenic agent bevacizumab may control vestibular schwannoma (VS) growth and promote hearing preservation in patients with neurofibromatosis type 2 (NF2). However, such metadata has yet to be consolidated, as well as its side-effect profile yet to be fully understood. Our aim was to pool systematically-identified metadata in the literature and substantiate the clinical efficacy and safety of bevacizumab with respect to radiographic tumor response, hearing, and treatment outcomes.
Multicenter, Prospective, Phase II and Biomarker Study of High-Dose Bevacizumab as Induction Therapy in Patients With Neurofibromatosis Type 2 and Progressive Vestibular Schwannoma. [2020]Bevacizumab treatment at 7.5 mg/kg every 3 weeks results in improved hearing in approximately 35%-40% of patients with neurofibromatosis type 2 (NF2) and progressive vestibular schwannomas (VSs). However, the optimal dose is unknown. In this multicenter phase II and biomarker study, we evaluated the efficacy and safety of high-dose bevacizumab in pediatric and adult patients with NF2 with progressive VS.
Aprepitant in the Treatment of Subacute Sclerosing Panencephalitis: A Randomized, Double-Blind, Placebo-Controlled Study. [2021]Aprepitant is a neurokinin-1 receptor antagonist approved for the treatment of chemotherapy-induced nausea. We aimed to investigate the safety and efficacy of aprepitant in patients with subacute sclerosing panencephalitis.
Antiemetic regimen with aprepitant in the prevention of chemotherapy-induced nausea and vomiting: An updated systematic review and meta-analysis. [2022]To systematically evaluate the efficacy and safety of antiemetic regimen with aprepitant in the prevention of chemotherapy-induced nausea and vomiting (CINV) and provide updated information for clinical practice.