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Safety, Tolerability and Efficacy for CGF166 in Patients With Unilateral or Bilateral Severe-to-profound Hearing Loss

Phase 1
Completed
Conditions
Unilateral Severe to Profound Hearing Loss OR Bilateral Severe to Profound Hearing Loss
Interventions
Registration Number
NCT02132130
Lead Sponsor
Novartis Pharmaceuticals
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
22
Inclusion Criteria

Not provided

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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
CGF166 dose 40 uLCGF166single dose volume #3
CGF166 dose 20 uLCGF166single dose volume #1
CGF166 dose 30 and 40 uLCGF166single dose volume #2
CGF166 dose 60 uLCGF166single dose volume #4
CFG166 dose 30 uLCGF166Single dose volume #5
Primary Outcome Measures
NameTimeMethod
Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study VisitWeek 52

Summary of change from baseline in pure tone audiometry air conduction threshold by frequency for last study visit is presented in table below.

Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study VisitWeek 52

Summary of change from baseline in Non-treated ear's pure tone audiometry air conduction threshold by frequency for last study visit is presented in table below.

Number of Participants With Adverse Eventsweek 52

AE tables are below in the Adverse Events section of this report.

Number of Adverse Eventsweek 52

AE tables are below in the Adverse Events section of this report.

Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment ValuesDays 29, 57, 85, 113, 141, 169, 358, 537, 600

Summary of pure tone audiometry air conduction thresholds at frequency 0.125 KHz

Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and FrequencyDays 29, 57, 85, 113, 141, 169, 358,537, EoS

Summary of pure tone audiometry bone conduction thresholds by time and frequency 0.250 KHz

Secondary Outcome Measures
NameTimeMethod
Number of Participants With Response in Vestibular Function in Treated Ear Compared to Pretreatment Values24 months

Response in vestibular assessments (Head impulse test (HIT), Vestibular evoked myogenic potential (VEMP), Subjective visual vertical (SVV)) to CGF166.

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 Ear24 months

Clinically signficant speech recognition improvement (word and/or sentence) following treatment. The individual auditory assessments were speech audiometry, AzBio sentence test, consonant nucleus consonant test, word recognition, Hearing-in-Noise Test (HINT), Brainstem auditory evoked response evaluations (BAER), Distortion product otoacoustic emission testing (DPOE) and shoebox audiometry.

Number of Participants With Change in Brainstem Auditory Evoked Responses (BAER) Compared to Pretreatment Values24 months

BAERs was assessed with standard techniques for clinically significant threshold improvements compared to baseline levels.

Trial Locations

Locations (1)

Novartis Investigative Site

🇺🇸

Portland, Oregon, United States

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