Patient case: 68-year-old male with melanoma; genetic feature: PTEN loss of function

Clinical trial: Safety, Tolerability and Efficacy for CGF166 in Patients With Bilateral Severe-to-profound Hearing Loss

Summary: The goal of the study is to evaluate the safety, tolerability, and the potential ability of CGF166 delivered through IL-infusion to improve hearing and vestibular function. CGF166 is a recombinant adenovirus 5 (Ad5) vector containing a cDNA encoding the human Atonal transcription factor (Hath1).

Detailed description: The study will evaluate the safety, tolerability, and potential efficacy of CGF166 and the associated delivery procedures in patients with severe-to-profound bilateral hearing loss. Eligible patients are required to have documented, non-fluctuating hearing loss. Part A will include a safety and tolerability cohort (N=3). Patient dosing will be staggered; dosing the next patient in a cohort will be based on a safety review of all available data through 4 weeks post-dose of the previously dosed patient(s). Part B includes a volumetric escalation design to evaluate infusion volumes of the same CGF166 concentration (5.0 x 10E11vp/mL) in 4 cohorts of patients (n=3/cohort; total of 12 patients). Part C is an expansion cohort of the highest safe and tolerable dose identified in Part B, for further assessment of efficacy.

Eligibility: For all Parts A, B and C of the study,
  Inclusion criteria:
  1. Written informed consent must be obtained before any assessment is performed.
  2. For all Parts (A, B and C) of the study, male or female patients, 18 to 75 years old, inclusive, with severe-to-profound bilateral hearing loss with intact vestibular function in the non operative ear. Non-fluctuating severe-to-profound hearing loss is required for the study ear and is defined as:
  -  PTA within 10 dB of the PTA obtained at least 11 months previously.
  -  Word recognition within 20% of previous test at least 11 months previously [AAO HNS Hearing Classification System]
  3. Candidate ear ("study ear"): Minimal residual hearing based on the pure tone average of 0.5, 1, 2, and 4 kHz thresholds of ≤110 dB HL
  4. Candidate ear ("study ear"): Pure tone audiometric thresholds of ≥50 dB HL for each testable octave frequency of 0.125 and 0.250 kHz, ≥ 70 dB HL for each testable octave frequency from 0.5 through 8 kHz and sentence recognition scores ≤50% at screening. Subject responses will be monitored for vibrotactile sensation, particularly for the low-frequency stimuli (e.g., 125 and 250 Hz). A frequency that elicits vibrotactile responses at levels below 70 dB HL will be considered "not testable" for hearing threshold and only those frequencies that are testable for hearing threshold will be considered for patient inclusion/exclusion in the study.
  5. Contralateral ear ("non-study ear"): Despite use of a hearing aid, must meet cochlear implantation criteria. Pure tone average over 0.5/1/2/4 kHz of ≥70 dB HL and ≤110 dB HL and sentence recognition using the AzBio test ≤60% at screening
  6. Patients with intact vestibular function in at least one ear (non-study ear) as measured by vestibulo-ocular reflex, caloric nystagmography, or vestibular evoked myogenic potential (VEMP)
  7. Able to communicate well with the investigator, to understand and comply with the requirements of the study
  8. Meet surgical requirements/eligibility (including MRI scan within 3 months or at screening to confirm suitability for inner ear surgery)
  9. Patients must weigh at least 40 kg to participate in the study, and must have a body mass index (BMI) <45 kg/m2. BMI = Body weight (kg) / [Height (m)]2
  Exclusion Criteria:
  1. Patients with hearing loss caused by genetic/developmental disorders, e.g., cochlea aplasia or autoimmune ear disease
  2. Patients with existing conductive hearing loss or mixed hearing loss as judged by the Principal Investigator following a thorough review of all of the trial hearing assessments, especially immittance testing as part of DPAOE;
  3. Patients with cochlear implants or past cochlear implant in the candidate study ear
  4. Hearing loss due to any other cause that would not be expected to respond to hair cell regeneration, for example mechanical trauma or central auditory lesions or lack of an auditory nerve
  5. Patients who will require ototoxic drugs as routine therapy over the course of the study, such as oncology patients on platinum-based chemotherapy
  6. Any contraindication to the planned surgery or anesthesia as determined by the surgeon or anesthesiologist
  7. Previous surgery in the study ear
  8. Any otological history, such as chronic otitis, cholesteatoma, tympanic membrane perforation, that suggests poor candidacy for cochlear implant or inner ear surgery or suggests potential interference with study auditory or vestibular function tests
  9. Pregnant women
  10. Abnormal vital signs and/or ECG that suggest potential contraindication for planned study anesthesia
  11. Past serious adverse reaction to anesthesia
  12. Meniere's Disease
  13. History of radiation therapy to the head and neck
  14. Participation in a clinical trial within the last 30 days
  15. Immunocompromised patients, as judged by the investigators based on patient history, physical exam and CBC

Relevance to patient case: not relevant