A phase I/II non-randomized, controlled trial, evaluating the safety and efficacy of neurotrophin gene therapy delivered during cochlear implant surgery

Not Applicable

Completed

• Conditions: hearing loss; deafness; Ear - Deafness

• Registration Number: ACTRN12618001556235
• Lead Sponsor: SW Sydney

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-09-17
• Study Completion: 2024-08-28
• Last Update Posted: 9 September 2024

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

1. Informed consent is obtained before any trial-related activities are performed (trial-related activities are any procedure/s that would not have been performed during the normal management of the subject)
2. Male or female, aged 21 to 85 years old, inclusive.
3. Mobile, able, and willing to participate in the study.
4. Subjects with severe to profound bilateral hearing loss of less than thirty years. Pure tone audiometric thresholds of greater than or equal to 70 dB HL for each testable octave frequency from 250 Hz through to 8 kHz and CNC sentence recognition scores less than or equal to 80%, or word scores less than or equal to 50%. Subject responses will be monitored for vibrotactile sensation, particularly for the low-frequency stimuli (e.g. 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. Able to communicate well with the investigator, to understand and comply with the requirements of the study
6. Meet surgical requirements/eligibility
7. Subjects must weigh at least 40 kg to participate in the study, and must have a body mass index (BMI) of less than 45 kg/m2. BMI = Body weight (kg) / [Height (m)]2

Exclusion Criteria

1.Patients conditions involving cochlea abnormalities that would prevent the insertion of an array or cause excessive perilymph flow during surgery, as judged by the Principal Investigator (e.g. cochlea aplasia, and bone formation within the cochlea)
2.Patients with severe to profound hearing loss diagnosed within the first five years of life
3.Patients with indication of tympanic membrane or middle ear abnormalities as judged by the Principal Investigator
4.Patients with an existing cochlear implant or past cochlear implant in the candidate study ear
5.Patients with serious concomitant conditions (such as a history of a serious cardiac event, renal impairment, hepatic impairment, major surgery etc.)
6.Patients with pacemakers and defibrillators
7.Patients with concomitant malignant or pre-malignant conditions, excluding treated skin cancers
8.Patients with a condition predisposing to, or with a history of, or experiencing neural line tumours
9.Hearing loss due to any other cause that would not be expected to respond to cochlear implantation, for example central auditory lesions or lack of an auditory nerve
10.Patients who will require ototoxic drugs as routine therapy over the course of the study, such as oncology patients on platinum-based chemotherapy
11.Vestibular disequilibrium which in the opinion of the investigator would be incompatible with planned vestibular assessments.
12.Any contraindication to the planned surgery or anaesthesia as determined by the surgeon or anaesthetist
13.Previous surgery or otologic history in the study ear, as judged by the investigator that would affect the surgical implantation of the cochlear implant
14.Mental incapacity, unwillingness or language barrier precluding adequate understanding of the trial procedure or cooperation with the trial site personnel, as judged by the investigator that may affect their ability to take part in the trial.
15.Pre-operative CNC sentence recognition scores of greater than 50%
16.Females of childbearing potential who are pregnant, breast-feeding, or intend on becoming pregnant within the duration of the study
17.Involvement in any interventional clinical trial within 30 days prior to this trial.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Primary outcome:<br>Safety (composite)<br>- Number of patients reported with total adverse events (AE) - any untoward medical occurrence in a participant enrolled into this study regardless of its causal relationship to study treatment., <br>- Number of serious adverse events - A serious adverse event (SAE) is defined as a AE that: Results in death, is immediately life threatening, requires inpatient hospitalisation, requires prolongation of existing hospitalisation, results in persistent or significant disability or incapacity, is a congenital abnormality or birth defect <br><br>Adverse events and serious adverse events are being assessed by medical records and patient reporting.<br>[ Iterative studies out to 12 months: -1, 0, 1, 2, 3, 4, 6, 12, 26, 38, 52 weeks]

Secondary Outcome Measures

Name	Time	Method
Pure tone audiometry (PTA) is a psychometric assessment of hearing sensitivity. This is used in the initial patient screening for recruitment as a criteria for admission into the trial. The hearing loss as measured by PTA hearing loss (HL) threshold, is required to be of greater or equal than 70 dB HL for each testable octave frequency from 250Hz through to 4 kHz. <br><br>[ Iterative studies out to 12 months: -1, 0, 1, 2, 3, 4, 6, 12, 26, 38, 52 weeks];CNC word recognition test[ Iterative studies out to 12 months: -1, 0, 1, 2, 3, 4, 6, 12, 26, 38, 52 weeks];Cochlear nerve function (neural response telemetry)<br>[ Iterative studies out to 12 months: -1, 0, 1, 2, 3, 4, 6, 12, 26, 38, 52 weeks];Auditory brainstem response (eABR)<br>[ Iterative studies out to 12 months: -1, 0, 1, 2, 3, 4, 6, 12, 26, 38, 52 weeks]