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

• ClinicalTrials.gov Identifier: NCT02132130
• Recruitment Status: Completed
• First Posted: May 7, 2014
• Results First Posted: March 30, 2021
• Last Update Posted: October 8, 2021
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Unilateral Severe to Profound Hearing Loss OR Bilateral Severe to Profound Hearing Loss	Drug: CGF166	Phase 1; Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 22 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• 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
• Actual Study Start Date: June 23, 2014
• Actual Primary Completion Date: December 9, 2019
• Actual Study Completion Date: December 9, 2019

Arms and Interventions

Arm	Intervention/treatment
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 30 and 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 40 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 60 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: CFG166 dose 30 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

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Adverse Events [ Time Frame: week 52 ]
   AE tables are below in the Adverse Events section of this report.
2. Number of Adverse Events [ Time Frame: week 52 ]
   AE tables are below in the Adverse Events section of this report.
3. Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values [ Time Frame: Days 29, 57, 85, 113, 141, 169, 358, 537, 600 ]
   Summary of pure tone audiometry air conduction thresholds at frequency 0.125 KHz
4. Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency [ Time Frame: Days 29, 57, 85, 113, 141, 169, 358,537, EoS ]
   Summary of pure tone audiometry bone conduction thresholds by time and frequency 0.250 KHz
5. Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit [ Time Frame: Week 52 ]
   Summary of change from baseline in pure tone audiometry air conduction threshold by frequency for last study visit is presented in table below.
6. Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit [ Time Frame: Week 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.

Secondary Outcome Measures :

1. Number of Participants With Change in Brainstem Auditory Evoked Responses (BAER) Compared to Pretreatment Values [ Time Frame: 24 months ]
   BAERs was assessed with standard techniques for clinically significant threshold improvements compared to baseline levels.
2. Number of Participants With Response in Vestibular Function in Treated Ear Compared to Pretreatment Values [ Time Frame: 24 months ]
   Response in vestibular assessments (Head impulse test (HIT), Vestibular evoked myogenic potential (VEMP), Subjective visual vertical (SVV)) to CGF166.
3. 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 [ Time Frame: 24 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• 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 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

Contacts and Locations

Locations

United States, Kansas

Novartis Investigative Site

Kansas City, Kansas, United States, 66160

United States, Maryland

Novartis Investigative Site

Baltimore, Maryland, United States, 21287

United States, New York

Novartis Investigative Site

New York, New York, United States, 10032

United States, Oregon

Novartis Investigative Site

Portland, Oregon, United States, 97239

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):

Study Protocol  [PDF] April 30, 2019

Statistical Analysis Plan  [PDF] August 17, 2018

More Information

Additional Information:

A Plain Language Trial Summary is available on novartisclinicaltrials.com 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02132130
• Other Study ID Numbers: CCGF166X2201
• First Posted: May 7, 2014
• Results First Posted: March 30, 2021
• Last Update Posted: October 8, 2021
• Last Verified: October 2021

Individual Participant Data (IPD) Sharing Statement:

• 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; unilateral hearing loss; bilateral hearing loss; balance; vestibular; cochlear implant; hearing restoration

Additional relevant MeSH terms:

Hearing Loss; Deafness; Hearing Disorders; Ear Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases