Try our beta test site
IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2017 by Novartis ( Novartis Pharmaceuticals )
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT02132130
First received: May 5, 2014
Last updated: April 20, 2017
Last verified: April 2017
  Purpose
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).

Condition Intervention Phase
Bilateral Severe to Profound Hearing Loss
Drug: CGF166
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Novartis ( Novartis Pharmaceuticals ):

Primary Outcome Measures:
  • Number of patients reported with total adverse events, serious adverse events and death as an assessment of safety and tolerability [ Time Frame: 6 months ]
  • Change in pure tone audiometry compared to pretreatment values [ Time Frame: 6 months ]
    Sensory thresholds at pure tone frequencies from 0.125 KHz through 16 KHz will be measured using standard audiometric techniques.


Secondary Outcome Measures:
  • Change in otoacoustic emission (OAE) testing compared to pretreatment values [ Time Frame: 6 months ]
    Standard OAE assessments will be performed to evaluate for a clinically significant improvement in signal to noise ratio 6 months following treatment.

  • Change in brainstem auditory evoked responses (BAER) compared to pretreatment values [ Time Frame: 6 months ]
    BAERs will be assessed with standard techniques for clinically significant threshold improvements compared to baseline levels.

  • effects of CGF166 on various assessments of vestibular function compared to pretreatment values [ Time Frame: 6 months ]
    Assessments of the vestibular organs for clinically relevant functional improvement

  • Changes in auditory functions (speech recognition) and vestibular functions before and after IL infusion of CGF166 between the study ear and the contralateral ear [ Time Frame: 6 months ]
    Clinically signficant speech recognition improvement (word and/or sentence) following treatment


Estimated Enrollment: 45
Actual Study Start Date: October 9, 2014
Estimated Study Completion Date: June 12, 2019
Estimated Primary Completion Date: June 12, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CGF166 dose 20 uL
single dose volume #1
Drug: CGF166
CGF166 is a recombinant adenovirus 5 (Ad5) vector containing the human Atonal transcription factor (Hath1) cDNA for administration via intra-labyrinthine infusion
Experimental: CGF166 dose 40 uL
single dose volume #2
Drug: CGF166
CGF166 is a recombinant adenovirus 5 (Ad5) vector containing the human Atonal transcription factor (Hath1) cDNA for administration via intra-labyrinthine infusion
Experimental: CGF166 dose 60 uL
single dose volume #3
Drug: CGF166
CGF166 is a recombinant adenovirus 5 (Ad5) vector containing the human Atonal transcription factor (Hath1) cDNA for administration via intra-labyrinthine infusion
Experimental: CGF166 dose 80 uL
single dose volume #4
Drug: CGF166
CGF166 is a recombinant adenovirus 5 (Ad5) vector containing the human Atonal transcription factor (Hath1) cDNA for administration via intra-labyrinthine infusion
Experimental: CGF166 dose 90 uL
Single dose volume #5
Drug: CGF166
CGF166 is a recombinant adenovirus 5 (Ad5) vector containing the human Atonal transcription factor (Hath1) cDNA for administration via intra-labyrinthine infusion
Experimental: CFG166 dose TBD uL
Single dose volume #6
Drug: CGF166
CGF166 is a recombinant adenovirus 5 (Ad5) vector containing the human Atonal transcription factor (Hath1) cDNA for administration via intra-labyrinthine infusion

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

Ages Eligible for Study:   21 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02132130

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682 trialandresults.registries@novartis.com
Contact: Novartis Pharmaceuticals

Locations
United States, Kansas
Novartis Investigative Site Recruiting
Kansas City, Kansas, United States, 66160
United States, Maryland
Novartis Investigative Site Recruiting
Baltimore, Maryland, United States, 21287
United States, New York
Novartis Investigative Site Recruiting
New York, New York, United States, 10032
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02132130     History of Changes
Other Study ID Numbers: CCGF166X2201
Study First Received: May 5, 2014
Last Updated: April 20, 2017
Individual Participant Data  
Plan to Share IPD: Undecided
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com


Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
gene therapy
hearing loss
balance
vestibular
cochlear implant

Additional relevant MeSH terms:
Hearing Loss
Deafness
Hearing Disorders
Ear Diseases
Otorhinolaryngologic Diseases
Sensation Disorders
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms

ClinicalTrials.gov processed this record on May 25, 2017