Clinical trial NCT02132130: Safety, Tolerability and Efficacy for CGF166 in Patients With Unilateral or Bilateral Severe-to-profound Hearing Loss
Official title: A Three-part, Multicenter, Open Label, Single Dose Study to Assess the Safety, Tolerability, and Efficacy of Intra Labyrinthine (IL) CGF166 in Patients With Severe-to-profound Hearing Loss
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Unilateral Severe to Profound Hearing Loss OR Bilateral Severe to Profound Hearing Loss
Keywords: gene therapy
unilateral hearing loss
bilateral hearing loss
balance
vestibular
cochlear implant
hearing restoration
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2014-05-07
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Detailed description: This study evaluated the safety, tolerability, and potential efficacy of CGF166 and the associated delivery procedures in patients with severe-to-profound unilateral or bilateral hearing loss. Eligible patients were required to have documented, non-fluctuating hearing loss.

Eligibility criteria: 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 or unilateral hearing loss with intact vestibular function in the nonoperative 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
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.

6. Patients with intact vestibular function in at least one ear (non-study ear) as measured by vestibular evoked myogenic potential (VEMP) 7. Able to communicate well with the investigator, to understand and comply with the requirements of the study 8. MRI scan within 6 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
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;
3. Patients with a history of cochlear implant in the 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, for example cystic fibrosis patients
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

Primary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: week 52
measure: Number of Adverse Events
timeFrame: week 52
measure: Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values
timeFrame: Days 29, 57, 85, 113, 141, 169, 358, 537, 600
measure: Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency
timeFrame: Days 29, 57, 85, 113, 141, 169, 358,537, EoS
measure: Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit
timeFrame: Week 52
measure: Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit
timeFrame: Week 52
Secondary outcomes:
measure: Number of Participants With Change in Brainstem Auditory Evoked Responses (BAER) Compared to Pretreatment Values
timeFrame: 24 months
measure: Number of Participants With Response in Vestibular Function in Treated Ear Compared to Pretreatment Values
timeFrame: 24 months
measure: Number of Participants With Changes in Auditory Functions (Speech Recognition) and Vestibular Functions Before and After IL Infusion of CGF166 Between the Study Ear and the Contralateral Ear
timeFrame: 24 months
Other outcomes:
Locations:
city: Kansas City
country: United States
facility: Novartis Investigative Site
state: Kansas
city: Baltimore
country: United States
facility: Novartis Investigative Site
state: Maryland
city: New York
country: United States
facility: Novartis Investigative Site
state: New York
city: Portland
country: United States
facility: Novartis Investigative Site
state: Oregon
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Plontke SK. Otology Jubilee: 150 years of the Archiv fur Ohrenheilkunde "Where do we come from?--Where are we?--Where are we going?". Eur Arch Otorhinolaryngol. 2015 Jun;272(6):1301-3. doi: 10.1007/s00405-015-3538-4. Epub 2015 Feb 18. No abstract available.