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CompletedNCT02132130Updated Oct 8, 2021Results posted

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

A Phase 1/2 interventional study of CGF166 in Unilateral Severe to Profound Hearing Loss OR Bilateral Severe to Profound Hearing Loss, sponsored by Novartis Pharmaceuticals. Completed at 4 sites in United States. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2021-10-08.

Sponsored by Novartis Pharmaceuticals · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
22
Allocation
Non-randomized
Ages
18 Years to 75 Years
Sex
All
01

Study 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).

Read the 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.

02

Conditions studied

  • 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
03

In context

Hearing Loss

1,092 studies on the registry are indexed under Hearing Loss; 235 are open to participants now.

This study's enrollment of 22 is below the median of 40 across 764 interventional studies indexed under Hearing Loss.

Browse Hearing Loss studies →

Lead sponsor

Novartis Pharmaceuticals is the lead sponsor of 2,673 studies on the registry; 228 are open to participants now.

Of its 576 completed or terminated interventional studies of FDA-regulated products, 431 (75%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

For all Parts A, B and C of the study,

Inclusion criteria

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.
  1. 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

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
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Single group
Masking
None (open label)
Enrollment
22 participants (actual)

Study arms

  • Experimental
    CGF166 dose 20 uL

    single dose volume #1

    Drug: CGF166

  • Experimental
    CGF166 dose 30 and 40 uL

    single dose volume #2

    Drug: CGF166

  • Experimental
    CGF166 dose 40 uL

    single dose volume #3

    Drug: CGF166

  • Experimental
    CGF166 dose 60 uL

    single dose volume #4

    Drug: CGF166

  • Experimental
    CFG166 dose 30 uL

    Single dose volume #5

    Drug: CGF166

Interventions

  • DrugCGF166

    CGF166 is a recombinant adenovirus 5 (Ad5) vector containing the human Atonal transcription factor (Hath1) cDNA for administration via intra-labyrinthine infusion

06

What researchers measure

Primary outcomes

  1. Number of Participants With Adverse Events

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

    Time frame: week 52

  2. Number of Adverse Events

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

    Time frame: week 52

  3. Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values

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

    Time frame: Days 29, 57, 85, 113, 141, 169, 358, 537, 600

  4. Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency

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

    Time frame: Days 29, 57, 85, 113, 141, 169, 358,537, EoS

  5. Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit

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

    Time frame: Week 52

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

    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.

    Time frame: Week 52

Secondary outcomes

  1. Number of Participants With Change in Brainstem Auditory Evoked Responses (BAER) Compared to Pretreatment Values

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

    Time frame: 24 months

  2. Number of Participants With Response in Vestibular Function in Treated Ear Compared to Pretreatment Values

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

    Time frame: 24 months

  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

    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.

    Time frame: 24 months

07

Results

Posted Mar 30, 2021

Participant flow

A total of 22 subjects were enrolled in the study, of which 19 completed the study and 2 subjects discontinued due to lost to follow-up and 1 subject withdrew consent

Participant flow — Overall Study
MilestoneCGF166 Dose 20 μLCGF166 Dose 30 μLCGF166 Dose 40 μLCGF166 Dose 60 μL
Started31243
Completed31042
Not completed0201
Withdrew: Lost to follow-up0200
Withdrew: Withdrawal by subject0001

Outcome measures

PrimaryNumber of Participants With Adverse Events

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

Time frame:
week 52
Reported as:
Count of participants · Participants
Number of Participants With Adverse Events
ParticipantsCGF166 Dose 20 μLCGF166 Dose 30 μLEdit Single Dose Volume #2CGF166 Dose 40 μLCGF166 Dose 60 μLTotal
Number of Participants With Adverse Events364316
PrimaryNumber of Adverse Events

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

Time frame:
week 52
Reported as:
Number · Adverse events
Number of Adverse Events
Adverse eventsCGF166 Dose 20 μLCGF166 Dose 30 μLCGF166 Dose 40 μLCGF166 Dose 60 μLTotal
Number of Adverse Events91613846
PrimarySummary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values

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

Time frame:
Days 29, 57, 85, 113, 141, 169, 358, 537, 600
Reported as:
Mean · DECIBELS
Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values
DECIBELSCGF166 Dose 20 μLCGF166 Dose 30 μLCGF166 Dose 40 μLCGF166 Dose 60 μLTotal
Baseline63.3 ± 18.9370.0 ± 14.6270.0 ± 20.4171.7 ± 16.0769.3 ± 15.38
Day 2961.7 ± 20.8270.4 ± 22.1085.0 ± 10.8075.0 ± 15.0072.5 ± 19.62
Day 5761.7 ± 20.8271.4 ± 15.3486.3 ± 8.5473.3 ± 15.2873.1 ± 15.85
Day 8561.7 ± 25.6666.3 ± 14.3688.8 ± 24.9675.0 ± 15.0073.6 ± 21.16
Day 11360.0 ± 27.8473.6 ± 14.3392.5 ± 23.6375.0 ± 15.0075.5 ± 19.55
Day 14160.0 ± 27.8468.8 ± 14.9391.3 ± 22.8773.3 ± 14.4374.3 ± 21.65
Day 169—72.1 ± 11.85—70.0 ± 7.0771.7 ± 10.61
Day 358—80.0 ± 14.14—72.5 ± 10.6177.5 ± 12.55
Day 537—82.5 ± 10.61—75.080.0 ± 8.66
Day 60060.0 ± 27.8477.5 ± 15.6893.8 ± 9.4682.5 ± 17.6878.7 ± 18.77
PrimarySummary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency

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

Time frame:
Days 29, 57, 85, 113, 141, 169, 358,537, EoS
Reported as:
Mean · decibels
Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency
decibelsCGF166 Dose 20 μLCGF166 Dose 30 μLCGF166 Dose 40 μLCGF166 Dose 60 μLTotal
Baseline55.0 ± 0.0064.2 ± 28.8387.5 ± 43.555.0 ± 0.0065.9 ± 28.81
Day 2955.0 ± 0.0073.8 ± 31.4963.8 ± 42.1155.0 ± 0.0066.8 ± 29.01
Day 5750.0 ± 8.6656.8 ± 7.8390.0 ± 40.4155.0 ± 0.0061.9 ± 21.99
Day 8548.3 ± 11.5590.0 ± 40.4190.0 ± 40.4151.7 ± 5.7772.9 ± 34.68
Day 11350.0 ± 8.6657.7 ± 23.1786.3 ± 45.1653.3 ± 2.8961.4 ± 27.26
Day 14146.7 ± 14.4351.3 ± 7.5090.0 ± 40.4151.7 ± 5.7761.4 ± 27.97
Day 1690 ± 048.6 ± 8.52—50.0 ± 7.0748.9 ± 7.82
Day 358—45.0 ± 8.16—55.00 ± 0.0048.3 ± 8.16
Day 537—50 ± 7.07—4046.7 ± 7.64
End of Study48.3 ± 11.5561.5 ± 22.3790.0 ± 40.4150.0 ± 7.0764.2 ± 27.50
PrimarySummary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit

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

Time frame:
Week 52
Reported as:
Mean · decibels
Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit
decibelsCGF166 Dose 20 μLCGF166 Dose 30 μLCGF166 Dose 40 μLCGF166 Dose 60 μLTotal
125 hz-4.2 ± 9.466.7 ± 10.1926.3 ± 17.025.0 ± 4.338.5 ± 13.88
250 Hz-3.3 ± 6.296.0 ± 9.2026.3 ± 26.650.8 ± 1.447.7 ± 15.52
500 Hz0 ± 5.007.7 ± 11.0026.3 ± 23.320.8 ± 1.449.1 ± 14.91
1,000 Hz-0.8 ± 3.828.1 ± 10.5116.9 ± 8.985.8 ± 1.448.2 ± 9.89
2,000 Hz0.8 ± 6.296.0 ± 11.406.9 ± 8.510.8 ± 3.824.8 ± 9.48
3,000 Hz2.5 ± 2.505.8 ± 11.6011.9 ± 11.06-4.2 ± 3.825.1 ± 10.59
4,000 Hz0.8 ± 1.444.4 ± 12.975.0 ± 4.08-0.8 ± 3.823.3 ± 9.83
6,000 Hz1.7 ± 2.893.3 ± 13.167.5 ± 15.001.7 ± 6.293.2 ± 11.60
8,000 Hz1.7 ± 2.892.9 ± 15.33-8.8 ± 17.504.2 ± 7.220.8 ± 13.94
PrimarySummary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit

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.

Time frame:
Week 52
Reported as:
Mean · decibels
Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit
decibelsCGF166 Dose 20 μLCGF166 Dose 30 μLCGF166 Dose 40 μLCGF166 Dose 60 μLTotal
125 hz-2.5 ± 6.611.7 ± 4.92-3.1 ± 2.39-1.7 ± 3.828.5 ± 4.87
250 Hz0 ± 8.662.3 ± 5.48-2.5 ± 3.540.8 ± 2.897.7 ± 5.45
500 Hz0.8 ± 1.446.0 ± 18.87-2.5 ± 3.54-1.7 ± 2.509.1 ± 14.32
1,000 Hz1.7 ± 2.891.7 ± 4.810 ± 2.04-1.7 ± 1.448.2 ± 3.83
2,000 Hz0.8 ± 2.890.2 ± 7.27-0.6 ± 2.39-2.5 ± 4.334.8 ± 5.66
3,000 Hz0 ± 5.000.2 ± 4.940.6 ± 1.25-7.5 ± 2.505.1 ± 4.84
4,000 Hz-2.5 ± 6.611.0 ± 3.761.3 ± 2.50-0.8 ± 6.293.3 ± 4.25
6,000 Hz-0.8 ± 1.44-0.6 ± 3.56-8.1 ± 11.79-1.7 ± 5.773.2 ± 6.19
8,000 Hz-3.3 ± 5.77-4.2 ± 10.78-8.8 ± 17.50-0.8 ± 6.290.8 ± 10.83
SecondaryNumber of Participants With Change in Brainstem Auditory Evoked Responses (BAER) Compared to Pretreatment Values

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

Time frame:
24 months
Reported as:
Count of participants · Participants
Number of Participants With Change in Brainstem Auditory Evoked Responses (BAER) Compared to Pretreatment Values
ParticipantsCGF166 Dose 20 μLCGF166 Dose 30 μLCGF166 Dose 40 μLCGF166 Dose 60 μLTotal
Number of Participants With Change in Brainstem Auditory Evoked Responses (BAER) Compared to Pretreatment Values00000
SecondaryNumber of Participants With Response in Vestibular Function in Treated Ear Compared to Pretreatment Values

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

Time frame:
24 months
Reported as:
Count of participants · Participants
Number of Participants With Response in Vestibular Function in Treated Ear Compared to Pretreatment Values
ParticipantsCGF166 Dose 20 μLCGF166 Dose 30 μLCGF166 Dose 40 μLCGF166 Dose 60 μLTotal
Number of Participants With Response in Vestibular Function in Treated Ear Compared to Pretreatment Values00000
SecondaryNumber 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

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.

Time frame:
24 months
Reported as:
Count of participants · Participants
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
ParticipantsCGF166 Dose 20 μLCGF166 Dose 30 μLCGF166 Dose 40 μLCGF166 Dose 60 μLTotal
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 Ear00000

Adverse events

Collected over Adverse events (AEs) were collected from first dose of study treatment until end of study treatment at 52 weeks. Non-serious events are listed at a 1% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
CGF166 20 μL0/3 (0%)0/3 (0%)3/3 (100%)
CGF166 30 μL0/12 (0%)0/12 (0%)6/12 (50%)
CGF166 40 μL0/4 (0%)0/4 (0%)4/4 (100%)
CGF166 60 μL0/3 (0%)0/3 (0%)3/3 (100%)
Most frequent other events
Showing 10 of 32
Most frequent other events
EventCGF166 20 μLCGF166 30 μLCGF166 40 μLCGF166 60 μL
HypoacusisEar and labyrinth disorders0/32/124/41/3
MyalgiaMusculoskeletal and connective tissue disorders0/30/120/42/3
Left ventricular hypertrophyCardiac disorders0/30/120/41/3
Ear haemorrhageEar and labyrinth disorders1/30/120/40/3
Ear painEar and labyrinth disorders1/30/120/40/3
VertigoEar and labyrinth disorders1/31/121/40/3
FatigueGeneral disorders1/30/120/40/3
Seasonal allergyImmune system disorders1/30/120/40/3
Otitis mediaInfections and infestations0/30/120/41/3
SinusitisInfections and infestations1/30/120/40/3

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)CGF166 Dose 20 μLCGF166 Dose 30 μLCGF166 Dose 40 μLCGF166 Dose 60 μLTotal
<=18 years00000
Between 18 and 65 years393217
>=65 years03115
Age, Continuous
Age, Continuous(Years)CGF166 Dose 20 μLCGF166 Dose 30 μLCGF166 Dose 40 μLCGF166 Dose 60 μLTotal
Mean39.0 ± 17.3550.8 ± 15.2052.8 ± 13.4051.3 ± 19.3049.6 ± 15.16
Sex: Female, Male
Sex: Female, Male(Participants)CGF166 Dose 20 μLCGF166 Dose 30 μLCGF166 Dose 40 μLCGF166 Dose 60 μLTotal
Female23117
Male193215
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)CGF166 Dose 20 μLCGF166 Dose 30 μLCGF166 Dose 40 μLCGF166 Dose 60 μLTotal
Caucasian3104320
Asian01001
Other01001
08

Study locations

4 sites
  • Novartis Investigative Site
    Kansas City, Kansas 66160, United States
  • Novartis Investigative Site
    Baltimore, Maryland 21287, United States
  • Novartis Investigative Site
    New York, New York 10032, United States
  • Novartis Investigative Site
    Portland, Oregon 97239, United States
09

References and documents

Publications

  • 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. PubMed 25690605 ↗

Study documents

  • Study protocol · Apr 30, 2019
  • Statistical analysis plan · Aug 17, 2018

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Undecided — 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

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Oct 8, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02132130
Lead sponsor
Novartis Pharmaceuticals
Responsible party
Sponsor
First posted
May 7, 2014
Start date
Jun 23, 2014
Primary completion
Dec 9, 2019
Completion
Dec 9, 2019
Results posted
Mar 30, 2021
Last update
Oct 8, 2021

Study contacts

Novartis Pharmaceuticals
study director · Novartis Pharmaceuticals

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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