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

This study is currently recruiting participants.
Verified April 2017 by Novartis ( Novartis Pharmaceuticals )
Sponsor:
ClinicalTrials.gov Identifier:
NCT02132130
First Posted: May 7, 2014
Last Update Posted: April 24, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
May 5, 2014
May 7, 2014
April 24, 2017
October 9, 2014
June 12, 2019   (Final data collection date for primary outcome measure)
  • 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.
Same as current
Complete list of historical versions of study NCT02132130 on ClinicalTrials.gov Archive Site
  • 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
  • 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 signfiicant speech recognition improvement (word and/or sentence) following treatment
Not Provided
Not Provided
 
Safety, Tolerability and Efficacy for CGF166 in Patients With Bilateral Severe-to-profound Hearing Loss
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
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).
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.
Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Bilateral Severe to Profound Hearing Loss
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 20 uL
    single dose volume #1
    Intervention: Drug: CGF166
  • Experimental: CGF166 dose 40 uL
    single dose volume #2
    Intervention: Drug: CGF166
  • Experimental: CGF166 dose 60 uL
    single dose volume #3
    Intervention: Drug: CGF166
  • Experimental: CGF166 dose 80 uL
    single dose volume #4
    Intervention: Drug: CGF166
  • Experimental: CGF166 dose 90 uL
    Single dose volume #5
    Intervention: Drug: CGF166
  • Experimental: CFG166 dose TBD uL
    Single dose volume #6
    Intervention: Drug: CGF166
Plontke SK. Otology Jubilee: 150 years of the Archiv für 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
45
June 12, 2019
June 12, 2019   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
21 Years to 75 Years   (Adult, Senior)
No
Contact: Novartis Pharmaceuticals 1-888-669-6682 trialandresults.registries@novartis.com
Contact: Novartis Pharmaceuticals
United States
 
 
NCT02132130
CCGF166X2201
No
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
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

Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
April 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP