Unilateral Severe to Profound Hearing Loss OR Bilateral Severe to Profound Hearing Loss
Conditions
Keywords
gene therapy, unilateral hearing loss, bilateral hearing loss, balance, vestibular, cochlear implant, hearing restoration
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.
Interventions
DRUGCGF166
CGF166 is a recombinant adenovirus 5 (Ad5) vector containing the human Atonal transcription factor (Hath1) cDNA for administration via intra-labyrinthine infusion
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 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. |
| Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values | Days 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 Frequency | 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 |
| Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 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. |
| Number of Participants With Adverse Events | week 52 | AE tables are below in the Adverse Events section of this report. |
| Number of Adverse Events | week 52 | AE tables are below in the Adverse Events section of this report. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Response in Vestibular Function in Treated Ear Compared to Pretreatment Values | 24 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 Ear | 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. |
| Number of Participants With Change in Brainstem Auditory Evoked Responses (BAER) Compared to Pretreatment Values | 24 months | BAERs was assessed with standard techniques for clinically significant threshold improvements compared to baseline levels. |
Countries
United States
Participant flow
Recruitment details
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
Pre-assignment details
Safety analysis set comprised all subjects who received study drug and with no protocol deviations having relevant impact on safety.
Participants by arm
| Arm | Count |
|---|---|
| CGF166 Dose 20 μL single dose volume #1 | 3 |
| CGF166 Dose 30 μL single dose volume #2 | 12 |
| CGF166 Dose 40 μL single dose volume #3 | 4 |
| CGF166 Dose 60 μL single dose volume #4 | 3 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 2 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | CGF166 Dose 20 μL | CGF166 Dose 30 μL | CGF166 Dose 40 μL | CGF166 Dose 60 μL | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 3 Participants | 1 Participants | 1 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 9 Participants | 3 Participants | 2 Participants | 17 Participants |
| Age, Continuous | 39.0 Years STANDARD_DEVIATION 17.35 | 50.8 Years STANDARD_DEVIATION 15.2 | 52.8 Years STANDARD_DEVIATION 13.4 | 51.3 Years STANDARD_DEVIATION 19.3 | 49.6 Years STANDARD_DEVIATION 15.16 |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Caucasian | 3 Participants | 10 Participants | 4 Participants | 3 Participants | 20 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 1 Participants | 1 Participants | 7 Participants |
| Sex: Female, Male Male | 1 Participants | 9 Participants | 3 Participants | 2 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 12 | 0 / 4 | 0 / 3 |
| other Total, other adverse events | 3 / 3 | 6 / 12 | 4 / 4 | 3 / 3 |
| serious Total, serious adverse events | 0 / 3 | 0 / 12 | 0 / 4 | 0 / 3 |
Outcome results
Primary
Number of Adverse Events
AE tables are below in the Adverse Events section of this report.
Time frame: week 52
Population: The Safety Analysis Set was comprised of all subjects that received study drug and with no protocol deviations having relevant impact on safety.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CGF166 Dose 20 μL | Number of Adverse Events | 9 Adverse events |
| CGF166 Dose 30 μLEdit Single Dose Volume #2 | Number of Adverse Events | 16 Adverse events |
| CGF166 Dose 40 μL | Number of Adverse Events | 13 Adverse events |
| CGF166 Dose 60 μL | Number of Adverse Events | 8 Adverse events |
| Total | Number of Adverse Events | 46 Adverse events |
Primary
Number of Participants With Adverse Events
AE tables are below in the Adverse Events section of this report.
Time frame: week 52
Population: The Safety Analysis Set was comprised of all subjects that received study drug and with no protocol deviations having relevant impact on safety.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CGF166 Dose 20 μL | Number of Participants With Adverse Events | 3 Participants |
| CGF166 Dose 30 μLEdit Single Dose Volume #2 | Number of Participants With Adverse Events | 6 Participants |
| CGF166 Dose 40 μL | Number of Participants With Adverse Events | 4 Participants |
| CGF166 Dose 60 μL | Number of Participants With Adverse Events | 3 Participants |
| Total | Number of Participants With Adverse Events | 16 Participants |
Primary
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
Population: Pharmacodynamics (PD) analysis set was comprised of all subjects with any available PD data, who received any study drug and experienced no protocol deviations with relevant impact on PD data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CGF166 Dose 20 μL | Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 125 hz | -2.5 decibels | Standard Deviation 6.61 |
| CGF166 Dose 20 μL | Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 2,000 Hz | 0.8 decibels | Standard Deviation 2.89 |
| CGF166 Dose 20 μL | Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 250 Hz | 0 decibels | Standard Deviation 8.66 |
| CGF166 Dose 20 μL | Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 3,000 Hz | 0 decibels | Standard Deviation 5 |
| CGF166 Dose 20 μL | Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 6,000 Hz | -0.8 decibels | Standard Deviation 1.44 |
| CGF166 Dose 20 μL | Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 500 Hz | 0.8 decibels | Standard Deviation 1.44 |
| CGF166 Dose 20 μL | Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 4,000 Hz | -2.5 decibels | Standard Deviation 6.61 |
| CGF166 Dose 20 μL | Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 1,000 Hz | 1.7 decibels | Standard Deviation 2.89 |
| CGF166 Dose 20 μL | Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 8,000 Hz | -3.3 decibels | Standard Deviation 5.77 |
| CGF166 Dose 30 μLEdit Single Dose Volume #2 | Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 6,000 Hz | -0.6 decibels | Standard Deviation 3.56 |
| CGF166 Dose 30 μLEdit Single Dose Volume #2 | Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 3,000 Hz | 0.2 decibels | Standard Deviation 4.94 |
| CGF166 Dose 30 μLEdit Single Dose Volume #2 | Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 4,000 Hz | 1.0 decibels | Standard Deviation 3.76 |
| CGF166 Dose 30 μLEdit Single Dose Volume #2 | Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 2,000 Hz | 0.2 decibels | Standard Deviation 7.27 |
| CGF166 Dose 30 μLEdit Single Dose Volume #2 | Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 1,000 Hz | 1.7 decibels | Standard Deviation 4.81 |
| CGF166 Dose 30 μLEdit Single Dose Volume #2 | Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 8,000 Hz | -4.2 decibels | Standard Deviation 10.78 |
| CGF166 Dose 30 μLEdit Single Dose Volume #2 | Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 250 Hz | 2.3 decibels | Standard Deviation 5.48 |
| CGF166 Dose 30 μLEdit Single Dose Volume #2 | Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 500 Hz | 6.0 decibels | Standard Deviation 18.87 |
| CGF166 Dose 30 μLEdit Single Dose Volume #2 | Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 125 hz | 1.7 decibels | Standard Deviation 4.92 |
| CGF166 Dose 40 μL | Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 3,000 Hz | 0.6 decibels | Standard Deviation 1.25 |
| CGF166 Dose 40 μL | Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 125 hz | -3.1 decibels | Standard Deviation 2.39 |
| CGF166 Dose 40 μL | Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 250 Hz | -2.5 decibels | Standard Deviation 3.54 |
| CGF166 Dose 40 μL | Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 500 Hz | -2.5 decibels | Standard Deviation 3.54 |
| CGF166 Dose 40 μL | Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 1,000 Hz | 0 decibels | Standard Deviation 2.04 |
| CGF166 Dose 40 μL | Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 2,000 Hz | -0.6 decibels | Standard Deviation 2.39 |
| CGF166 Dose 40 μL | Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 4,000 Hz | 1.3 decibels | Standard Deviation 2.5 |
| CGF166 Dose 40 μL | Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 6,000 Hz | -8.1 decibels | Standard Deviation 11.79 |
| CGF166 Dose 40 μL | Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 8,000 Hz | -8.8 decibels | Standard Deviation 17.5 |
| CGF166 Dose 60 μL | Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 1,000 Hz | -1.7 decibels | Standard Deviation 1.44 |
| CGF166 Dose 60 μL | Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 3,000 Hz | -7.5 decibels | Standard Deviation 2.5 |
| CGF166 Dose 60 μL | Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 500 Hz | -1.7 decibels | Standard Deviation 2.5 |
| CGF166 Dose 60 μL | Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 4,000 Hz | -0.8 decibels | Standard Deviation 6.29 |
| CGF166 Dose 60 μL | Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 250 Hz | 0.8 decibels | Standard Deviation 2.89 |
| CGF166 Dose 60 μL | Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 8,000 Hz | -0.8 decibels | Standard Deviation 6.29 |
| CGF166 Dose 60 μL | Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 6,000 Hz | -1.7 decibels | Standard Deviation 5.77 |
| CGF166 Dose 60 μL | Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 125 hz | -1.7 decibels | Standard Deviation 3.82 |
| CGF166 Dose 60 μL | Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 2,000 Hz | -2.5 decibels | Standard Deviation 4.33 |
| Total | Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 125 hz | 8.5 decibels | Standard Deviation 4.87 |
| Total | Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 1,000 Hz | 8.2 decibels | Standard Deviation 3.83 |
| Total | Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 3,000 Hz | 5.1 decibels | Standard Deviation 4.84 |
| Total | Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 500 Hz | 9.1 decibels | Standard Deviation 14.32 |
| Total | Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 2,000 Hz | 4.8 decibels | Standard Deviation 5.66 |
| Total | Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 8,000 Hz | 0.8 decibels | Standard Deviation 10.83 |
| Total | Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 6,000 Hz | 3.2 decibels | Standard Deviation 6.19 |
| Total | Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 4,000 Hz | 3.3 decibels | Standard Deviation 4.25 |
| Total | Summary of Change From Baseline in Non-treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 250 Hz | 7.7 decibels | Standard Deviation 5.45 |
Primary
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
Population: Pharmacodynamics (PD) analysis set was comprised of all subjects with any available PD data, who received any study drug and experienced no protocol deviations with relevant impact on PD data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CGF166 Dose 20 μL | Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 8,000 Hz | 1.7 decibels | Standard Deviation 2.89 |
| CGF166 Dose 20 μL | Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 2,000 Hz | 0.8 decibels | Standard Deviation 6.29 |
| CGF166 Dose 20 μL | Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 250 Hz | -3.3 decibels | Standard Deviation 6.29 |
| CGF166 Dose 20 μL | Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 3,000 Hz | 2.5 decibels | Standard Deviation 2.5 |
| CGF166 Dose 20 μL | Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 6,000 Hz | 1.7 decibels | Standard Deviation 2.89 |
| CGF166 Dose 20 μL | Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 500 Hz | 0 decibels | Standard Deviation 5 |
| CGF166 Dose 20 μL | Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 4,000 Hz | 0.8 decibels | Standard Deviation 1.44 |
| CGF166 Dose 20 μL | Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 1,000 Hz | -0.8 decibels | Standard Deviation 3.82 |
| CGF166 Dose 20 μL | Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 125 hz | -4.2 decibels | Standard Deviation 9.46 |
| CGF166 Dose 30 μLEdit Single Dose Volume #2 | Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 4,000 Hz | 4.4 decibels | Standard Deviation 12.97 |
| CGF166 Dose 30 μLEdit Single Dose Volume #2 | Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 3,000 Hz | 5.8 decibels | Standard Deviation 11.6 |
| CGF166 Dose 30 μLEdit Single Dose Volume #2 | Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 1,000 Hz | 8.1 decibels | Standard Deviation 10.51 |
| CGF166 Dose 30 μLEdit Single Dose Volume #2 | Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 2,000 Hz | 6.0 decibels | Standard Deviation 11.4 |
| CGF166 Dose 30 μLEdit Single Dose Volume #2 | Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 500 Hz | 7.7 decibels | Standard Deviation 11 |
| CGF166 Dose 30 μLEdit Single Dose Volume #2 | Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 8,000 Hz | 2.9 decibels | Standard Deviation 15.33 |
| CGF166 Dose 30 μLEdit Single Dose Volume #2 | Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 250 Hz | 6.0 decibels | Standard Deviation 9.2 |
| CGF166 Dose 30 μLEdit Single Dose Volume #2 | Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 125 hz | 6.7 decibels | Standard Deviation 10.19 |
| CGF166 Dose 30 μLEdit Single Dose Volume #2 | Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 6,000 Hz | 3.3 decibels | Standard Deviation 13.16 |
| CGF166 Dose 40 μL | Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 3,000 Hz | 11.9 decibels | Standard Deviation 11.06 |
| CGF166 Dose 40 μL | Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 125 hz | 26.3 decibels | Standard Deviation 17.02 |
| CGF166 Dose 40 μL | Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 250 Hz | 26.3 decibels | Standard Deviation 26.65 |
| CGF166 Dose 40 μL | Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 500 Hz | 26.3 decibels | Standard Deviation 23.32 |
| CGF166 Dose 40 μL | Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 1,000 Hz | 16.9 decibels | Standard Deviation 8.98 |
| CGF166 Dose 40 μL | Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 2,000 Hz | 6.9 decibels | Standard Deviation 8.51 |
| CGF166 Dose 40 μL | Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 4,000 Hz | 5.0 decibels | Standard Deviation 4.08 |
| CGF166 Dose 40 μL | Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 6,000 Hz | 7.5 decibels | Standard Deviation 15 |
| CGF166 Dose 40 μL | Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 8,000 Hz | -8.8 decibels | Standard Deviation 17.5 |
| CGF166 Dose 60 μL | Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 1,000 Hz | 5.8 decibels | Standard Deviation 1.44 |
| CGF166 Dose 60 μL | Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 3,000 Hz | -4.2 decibels | Standard Deviation 3.82 |
| CGF166 Dose 60 μL | Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 500 Hz | 0.8 decibels | Standard Deviation 1.44 |
| CGF166 Dose 60 μL | Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 4,000 Hz | -0.8 decibels | Standard Deviation 3.82 |
| CGF166 Dose 60 μL | Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 250 Hz | 0.8 decibels | Standard Deviation 1.44 |
| CGF166 Dose 60 μL | Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 8,000 Hz | 4.2 decibels | Standard Deviation 7.22 |
| CGF166 Dose 60 μL | Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 6,000 Hz | 1.7 decibels | Standard Deviation 6.29 |
| CGF166 Dose 60 μL | Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 125 hz | 5.0 decibels | Standard Deviation 4.33 |
| CGF166 Dose 60 μL | Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 2,000 Hz | 0.8 decibels | Standard Deviation 3.82 |
| Total | Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 125 hz | 8.5 decibels | Standard Deviation 13.88 |
| Total | Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 1,000 Hz | 8.2 decibels | Standard Deviation 9.89 |
| Total | Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 3,000 Hz | 5.1 decibels | Standard Deviation 10.59 |
| Total | Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 500 Hz | 9.1 decibels | Standard Deviation 14.91 |
| Total | Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 2,000 Hz | 4.8 decibels | Standard Deviation 9.48 |
| Total | Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 8,000 Hz | 0.8 decibels | Standard Deviation 13.94 |
| Total | Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 6,000 Hz | 3.2 decibels | Standard Deviation 11.6 |
| Total | Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 4,000 Hz | 3.3 decibels | Standard Deviation 9.83 |
| Total | Summary of Change From Baseline in Treated Ear's Pure Tone Audiometry Air Conduction Threshold by Frequency for Last Study Visit | 250 Hz | 7.7 decibels | Standard Deviation 15.52 |
Primary
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
Population: Pharmacodynamics (PD) analysis set was comprised of all subjects with any available PD data, who received any study drug and experienced no protocol deviations with relevant impact on PD data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CGF166 Dose 20 μL | Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values | Day 57 | 61.7 DECIBELS | Standard Deviation 20.82 |
| CGF166 Dose 20 μL | Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values | Day 141 | 60.0 DECIBELS | Standard Deviation 27.84 |
| CGF166 Dose 20 μL | Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values | Day 29 | 61.7 DECIBELS | Standard Deviation 20.82 |
| CGF166 Dose 20 μL | Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values | Day 113 | 60.0 DECIBELS | Standard Deviation 27.84 |
| CGF166 Dose 20 μL | Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values | Baseline | 63.3 DECIBELS | Standard Deviation 18.93 |
| CGF166 Dose 20 μL | Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values | Day 85 | 61.7 DECIBELS | Standard Deviation 25.66 |
| CGF166 Dose 20 μL | Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values | Day 600 | 60.0 DECIBELS | Standard Deviation 27.84 |
| CGF166 Dose 30 μLEdit Single Dose Volume #2 | Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values | Day 57 | 71.4 DECIBELS | Standard Deviation 15.34 |
| CGF166 Dose 30 μLEdit Single Dose Volume #2 | Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values | Day 600 | 77.5 DECIBELS | Standard Deviation 15.68 |
| CGF166 Dose 30 μLEdit Single Dose Volume #2 | Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values | Day 169 | 72.1 DECIBELS | Standard Deviation 11.85 |
| CGF166 Dose 30 μLEdit Single Dose Volume #2 | Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values | Day 85 | 66.3 DECIBELS | Standard Deviation 14.36 |
| CGF166 Dose 30 μLEdit Single Dose Volume #2 | Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values | Day 141 | 68.8 DECIBELS | Standard Deviation 14.93 |
| CGF166 Dose 30 μLEdit Single Dose Volume #2 | Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values | Day 113 | 73.6 DECIBELS | Standard Deviation 14.33 |
| CGF166 Dose 30 μLEdit Single Dose Volume #2 | Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values | Day 29 | 70.4 DECIBELS | Standard Deviation 22.1 |
| CGF166 Dose 30 μLEdit Single Dose Volume #2 | Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values | Baseline | 70.0 DECIBELS | Standard Deviation 14.62 |
| CGF166 Dose 30 μLEdit Single Dose Volume #2 | Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values | Day 537 | 82.5 DECIBELS | Standard Deviation 10.61 |
| CGF166 Dose 30 μLEdit Single Dose Volume #2 | Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values | Day 358 | 80.0 DECIBELS | Standard Deviation 14.14 |
| CGF166 Dose 40 μL | Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values | Day 141 | 91.3 DECIBELS | Standard Deviation 22.87 |
| CGF166 Dose 40 μL | Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values | Baseline | 70.0 DECIBELS | Standard Deviation 20.41 |
| CGF166 Dose 40 μL | Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values | Day 29 | 85.0 DECIBELS | Standard Deviation 10.8 |
| CGF166 Dose 40 μL | Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values | Day 57 | 86.3 DECIBELS | Standard Deviation 8.54 |
| CGF166 Dose 40 μL | Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values | Day 85 | 88.8 DECIBELS | Standard Deviation 24.96 |
| CGF166 Dose 40 μL | Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values | Day 113 | 92.5 DECIBELS | Standard Deviation 23.63 |
| CGF166 Dose 40 μL | Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values | Day 600 | 93.8 DECIBELS | Standard Deviation 9.46 |
| CGF166 Dose 60 μL | Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values | Day 113 | 75.0 DECIBELS | Standard Deviation 15 |
| CGF166 Dose 60 μL | Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values | Day 85 | 75.0 DECIBELS | Standard Deviation 15 |
| CGF166 Dose 60 μL | Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values | Day 141 | 73.3 DECIBELS | Standard Deviation 14.43 |
| CGF166 Dose 60 μL | Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values | Day 57 | 73.3 DECIBELS | Standard Deviation 15.28 |
| CGF166 Dose 60 μL | Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values | Day 169 | 70.0 DECIBELS | Standard Deviation 7.07 |
| CGF166 Dose 60 μL | Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values | Day 358 | 72.5 DECIBELS | Standard Deviation 10.61 |
| CGF166 Dose 60 μL | Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values | Day 29 | 75.0 DECIBELS | Standard Deviation 15 |
| CGF166 Dose 60 μL | Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values | Day 537 | 75.0 DECIBELS | — |
| CGF166 Dose 60 μL | Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values | Baseline | 71.7 DECIBELS | Standard Deviation 16.07 |
| CGF166 Dose 60 μL | Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values | Day 600 | 82.5 DECIBELS | Standard Deviation 17.68 |
| Total | Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values | Baseline | 69.3 DECIBELS | Standard Deviation 15.38 |
| Total | Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values | Day 85 | 73.6 DECIBELS | Standard Deviation 21.16 |
| Total | Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values | Day 358 | 77.5 DECIBELS | Standard Deviation 12.55 |
| Total | Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values | Day 57 | 73.1 DECIBELS | Standard Deviation 15.85 |
| Total | Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values | Day 113 | 75.5 DECIBELS | Standard Deviation 19.55 |
| Total | Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values | Day 141 | 74.3 DECIBELS | Standard Deviation 21.65 |
| Total | Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values | Day 600 | 78.7 DECIBELS | Standard Deviation 18.77 |
| Total | Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values | Day 537 | 80.0 DECIBELS | Standard Deviation 8.66 |
| Total | Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values | Day 169 | 71.7 DECIBELS | Standard Deviation 10.61 |
| Total | Summary of Pure Tone Audiometry in Treated Ear Compared to Pretreatment Values | Day 29 | 72.5 DECIBELS | Standard Deviation 19.62 |
Primary
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
Population: Pharmacodynamics (PD) analysis set was comprised of all subjects with any available PD data, who received any study drug and experienced no protocol deviations with relevant impact on PD data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CGF166 Dose 20 μL | Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency | Baseline | 55.0 decibels | Standard Deviation 0 |
| CGF166 Dose 20 μL | Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency | Day 113 | 50.0 decibels | Standard Deviation 8.66 |
| CGF166 Dose 20 μL | Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency | Day 29 | 55.0 decibels | Standard Deviation 0 |
| CGF166 Dose 20 μL | Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency | Day 141 | 46.7 decibels | Standard Deviation 14.43 |
| CGF166 Dose 20 μL | Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency | Day 57 | 50.0 decibels | Standard Deviation 8.66 |
| CGF166 Dose 20 μL | Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency | Day 169 | 0 decibels | Standard Deviation 0 |
| CGF166 Dose 20 μL | Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency | Day 85 | 48.3 decibels | Standard Deviation 11.55 |
| CGF166 Dose 20 μL | Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency | End of Study | 48.3 decibels | Standard Deviation 11.55 |
| CGF166 Dose 30 μLEdit Single Dose Volume #2 | Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency | Day 537 | 50 decibels | Standard Deviation 7.07 |
| CGF166 Dose 30 μLEdit Single Dose Volume #2 | Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency | Day 358 | 45.0 decibels | Standard Deviation 8.16 |
| CGF166 Dose 30 μLEdit Single Dose Volume #2 | Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency | Day 85 | 90.0 decibels | Standard Deviation 40.41 |
| CGF166 Dose 30 μLEdit Single Dose Volume #2 | Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency | Day 141 | 51.3 decibels | Standard Deviation 7.5 |
| CGF166 Dose 30 μLEdit Single Dose Volume #2 | Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency | Day 57 | 56.8 decibels | Standard Deviation 7.83 |
| CGF166 Dose 30 μLEdit Single Dose Volume #2 | Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency | Day 113 | 57.7 decibels | Standard Deviation 23.17 |
| CGF166 Dose 30 μLEdit Single Dose Volume #2 | Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency | End of Study | 61.5 decibels | Standard Deviation 22.37 |
| CGF166 Dose 30 μLEdit Single Dose Volume #2 | Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency | Day 169 | 48.6 decibels | Standard Deviation 8.52 |
| CGF166 Dose 30 μLEdit Single Dose Volume #2 | Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency | Day 29 | 73.8 decibels | Standard Deviation 31.49 |
| CGF166 Dose 30 μLEdit Single Dose Volume #2 | Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency | Baseline | 64.2 decibels | Standard Deviation 28.83 |
| CGF166 Dose 40 μL | Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency | Day 141 | 90.0 decibels | Standard Deviation 40.41 |
| CGF166 Dose 40 μL | Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency | Baseline | 87.5 decibels | Standard Deviation 43.5 |
| CGF166 Dose 40 μL | Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency | Day 29 | 63.8 decibels | Standard Deviation 42.11 |
| CGF166 Dose 40 μL | Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency | Day 57 | 90.0 decibels | Standard Deviation 40.41 |
| CGF166 Dose 40 μL | Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency | Day 85 | 90.0 decibels | Standard Deviation 40.41 |
| CGF166 Dose 40 μL | Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency | Day 113 | 86.3 decibels | Standard Deviation 45.16 |
| CGF166 Dose 40 μL | Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency | End of Study | 90.0 decibels | Standard Deviation 40.41 |
| CGF166 Dose 60 μL | Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency | Day 113 | 53.3 decibels | Standard Deviation 2.89 |
| CGF166 Dose 60 μL | Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency | Day 85 | 51.7 decibels | Standard Deviation 5.77 |
| CGF166 Dose 60 μL | Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency | Day 141 | 51.7 decibels | Standard Deviation 5.77 |
| CGF166 Dose 60 μL | Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency | Day 57 | 55.0 decibels | Standard Deviation 0 |
| CGF166 Dose 60 μL | Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency | Day 169 | 50.0 decibels | Standard Deviation 7.07 |
| CGF166 Dose 60 μL | Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency | Day 358 | 55.00 decibels | Standard Deviation 0 |
| CGF166 Dose 60 μL | Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency | Day 29 | 55.0 decibels | Standard Deviation 0 |
| CGF166 Dose 60 μL | Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency | Day 537 | 40 decibels | — |
| CGF166 Dose 60 μL | Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency | Baseline | 55.0 decibels | Standard Deviation 0 |
| CGF166 Dose 60 μL | Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency | End of Study | 50.0 decibels | Standard Deviation 7.07 |
| Total | Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency | Baseline | 65.9 decibels | Standard Deviation 28.81 |
| Total | Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency | Day 85 | 72.9 decibels | Standard Deviation 34.68 |
| Total | Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency | Day 358 | 48.3 decibels | Standard Deviation 8.16 |
| Total | Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency | Day 113 | 61.4 decibels | Standard Deviation 27.26 |
| Total | Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency | Day 141 | 61.4 decibels | Standard Deviation 27.97 |
| Total | Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency | Day 57 | 61.9 decibels | Standard Deviation 21.99 |
| Total | Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency | End of Study | 64.2 decibels | Standard Deviation 27.5 |
| Total | Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency | Day 537 | 46.7 decibels | Standard Deviation 7.64 |
| Total | Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency | Day 169 | 48.9 decibels | Standard Deviation 7.82 |
| Total | Summary Pure Tone Audiometry Bone Conduction Thresholds in Treated Ear by Time and Frequency | Day 29 | 66.8 decibels | Standard Deviation 29.01 |
Secondary
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
Population: PD analysis set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CGF166 Dose 20 μL | Number of Participants With Change in Brainstem Auditory Evoked Responses (BAER) Compared to Pretreatment Values | 0 Participants |
| CGF166 Dose 30 μLEdit Single Dose Volume #2 | Number of Participants With Change in Brainstem Auditory Evoked Responses (BAER) Compared to Pretreatment Values | 0 Participants |
| CGF166 Dose 40 μL | Number of Participants With Change in Brainstem Auditory Evoked Responses (BAER) Compared to Pretreatment Values | 0 Participants |
| CGF166 Dose 60 μL | Number of Participants With Change in Brainstem Auditory Evoked Responses (BAER) Compared to Pretreatment Values | 0 Participants |
| Total | Number of Participants With Change in Brainstem Auditory Evoked Responses (BAER) Compared to Pretreatment Values | 0 Participants |
Secondary
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
Population: PD analysis set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CGF166 Dose 20 μL | 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 | 0 Participants |
| CGF166 Dose 30 μLEdit Single Dose Volume #2 | 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 | 0 Participants |
| CGF166 Dose 40 μL | 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 | 0 Participants |
| CGF166 Dose 60 μL | 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 | 0 Participants |
| Total | 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 | 0 Participants |
Secondary
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
Population: PD Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CGF166 Dose 20 μL | Number of Participants With Response in Vestibular Function in Treated Ear Compared to Pretreatment Values | 0 Participants |
| CGF166 Dose 30 μLEdit Single Dose Volume #2 | Number of Participants With Response in Vestibular Function in Treated Ear Compared to Pretreatment Values | 0 Participants |
| CGF166 Dose 40 μL | Number of Participants With Response in Vestibular Function in Treated Ear Compared to Pretreatment Values | 0 Participants |
| CGF166 Dose 60 μL | Number of Participants With Response in Vestibular Function in Treated Ear Compared to Pretreatment Values | 0 Participants |
| Total | Number of Participants With Response in Vestibular Function in Treated Ear Compared to Pretreatment Values | 0 Participants |