Clinical Trials

Inclusion Criteria:

Type of Participant and Disease Characteristics

• Presence of unilateral progressive VS (defined as a single tumor with a documented ≥ 20% growth in volume on successive MRI scans that have occurred within 24 months of each other and a minimum of 6 months apart). The most recent MRI must have been obtained no more than 6 months prior to enrollment (and may be obtained during the screening period).
• The tumor must be larger than 2 mm in maximum dimension and must be visible on at least three slices in a single sequence on the most recent MRI scan.
• Profound hearing loss, defined as WRS of 40% or less (tested at a sound intensity level that achieves the maximum score) OR pure-tone audiometry thresholds of > 90 dB HL (across 250 to 8000 Hz), in the affected ear.

Age

• Age ≥ 18 years old.

Sex and Contraceptive/Barrier Requirements

• Participants of child-bearing potential agree to use effective contraceptive methods throughout the trial. Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies as described in the corresponding Informed Consent Form (ICF):
  • Females of child-bearing potential include those who have experienced menarche, and who are not postmenopausal or permanently sterilized (e.g., bilateral tubal occlusion, hysterectomy, or bilateral salpingectomy);
  • Males are considered to be of child-producing potential unless they have had a bilateral vasectomy with documented aspermia or a bilateral orchiectomy.

Informed Consent

• Participant willingness to comply with all trial requirements, as evidenced by successful completion of the informed consent process.

Long Term Follow-Up

• Participant willingness to participate in separate LTFU study protocol after completion of this trial.

Exclusion Criteria: 

Medical Conditions

• Participants with any of the following tumor characteristics: a. tumors of 1.5 cm or more (in the maximum dimension) in the CPA (excluding the IAC component); or b. tumors that have contact with the brainstem; or c. tumors for which an additional observation period of one year would put the participant at high risk for further tumor-related sequalae (apart from hearing loss or worsening of hearing loss).
• Prior diagnosis of NF2 and/or participants with bilateral VS.
• Prior surgery or radiation therapy for VS.
• Current diagnosis or history of juvenile cataract, glioma, ependymoma, neurofibroma, or more than one meningioma.
• Clinical history consistent with endolymphatic hydrops (documented fluctuating sensorineural hearing loss and episodic vertigo) in the affected ear.
• History of vestibular hypofunction in the unaffected ear.
• Profound hearing loss, defined as WRS of 40% or less (tested at a sound intensity level that achieves the maximum score) OR pure-tone audiometry thresholds of > 90 dB HL (across 250 to 8000 Hz), in the unaffected ear.
• Medical or psychological conditions that contraindicate undergoing surgery, general anesthesia, use of corticosteroids, and/or investigational gene therapy administration.
• Persistent hepatic dysfunction indicated by bilirubin > 1.5X the ULN, or AST > 2X the ULN, or ALT > 2X the ULN.
• Evidence of persistent coagulopathy indicated by platelet count of < 100,000/mL or prolongation (> ULN) of PT or aPTT.
• Anatomic abnormalities of the affected ear that preclude the surgical approach, e.g., canal atresia. A CT scan may be obtained at screening at the discretion of the Investigator to evaluate bony anatomy, cochlear patency, and/or to identify other anomalies that could preclude the surgical approach, if available imaging studies (e.g., MRI or CT scans) are indeterminate.
• Any contraindications to obtaining routine high-resolution MRIs with contrast (e.g., participants with renal failure, severe claustrophobia, or non-MRI compatible implants).
• Evidence of current middle ear effusion in the affected ear.
• Acute otitis media (AOM), or other similar infection that temporarily precludes the surgical approach, or history of such in the affected ear, within six weeks prior to administration (Day 0).
• History or current diagnosis of cerebrovascular disease.

Prior/Concomitant Therapy

• Prior middle or inner ear surgery in the affected ear within six months prior to administration (Day 0).
• Chronic corticosteroid use (systemic or oral) within six months prior to administration (Day 0).
• Known sensitivity or allergy to VEGF inhibitors or other medications planned for use in the peri-operative period.

Prior/Concurrent Clinical Trial Experience

• 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.

Other Exclusions

• Currently pregnant or lactating, or planning to attempt pregnancy (males or females), within the next year.
• Any other condition that would not allow the potential participant to complete followup examinations during the course of the trial and/or, in the opinion of the Investigator, makes the potential participant unsuitable for the trial.
• Unwillingness or inability of the potential participant to comply with all investigational requirements and follow up. If potential participants meet any exclusion criteria on initial screening, rescreening is permitted after the underlying cause has been addressed. Potential participants will not be excluded based on their sex, gender, race, or ethnicity.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 12/26/23. Questions regarding updates should be directed to the study team contact.