Hearing Loss, Sensorineural, Noise Induced Hearing Loss, Sudden Hearing Loss
Conditions
Keywords
Intratympanic administration, Restoration of hearing loss
Brief summary
This is a Phase 2, prospective, randomized, double-blind, placebo-controlled, single-dose, multicenter study to evaluate the efficacy of FX-322, administered by intratympanic injection, in adults with acquired sensorineural hearing loss (SNHL).
Detailed description
This is a Phase 2, prospective, randomized, double-blind, placebo-controlled, single-dose, multicenter study to evaluate the efficacy of FX-322, administered by intratympanic injection, in adults with acquired sensorineural hearing loss (SNHL). Previous human studies in subjects 18 to 65 years inclusive (FX-322-103, FX-322-201, FX-322-111) and subjects 66-85 inclusive (FX-322-112) demonstrated that a single dose FX-322 was well tolerated in patients with acquired SNHL with no treatment-related serious adverse events. Adverse events in these studies were generally common to and associated with the intratympanic injection procedure with mild and transient discomfort in patients both with the drug and the placebo. Frequency Therapeutics' Investigators intend to evaluate efficacy with a single dose of FX-322 in subjects 18 to 65 years inclusive with acquired SNHL.
Interventions
DRUGFX-322
Active Comparator
DRUGPlacebo
Placebo
Sponsors
Frequency Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Subject has read and voluntarily signed the Informed Consent Form (ICF) after all questions have been answered and prior to any study-mandated procedure. 2. Adult aged 18-65 years inclusive at Screening. 3. Documented medical history consistent with acquired, adult onset, sensorineural hearing loss associated with noise-induced SNHL (NIHL) or idiopathic sudden SNHL (SSNHL) (documented audiogram at least 6 months prior to screening required). 4. A pure tone average at the Screening Visit of 35-85 dB at 500Hz, 1000Hz, 2000Hz, and 4000Hz in the ear to be injected. 5. Ability to communicate well with the Investigator and is willing to comply with and complete all the study procedures. 6. Female subjects must be of non-childbearing potential or will need to utilize two methods of highly effective contraception during the study participation (e.g. hormonal contraception and condom or an intrauterine device and condom) or remain abstinent. Male subjects should use condoms with spermicide during the course of the study or remain abstinent. Subjects should not donate sperm or ova during the study period. 7. Have met additional masked criteria as determined by the Electronic Data Capture system.
Exclusion criteria
1. Subject has previously been randomized in a FX-322 clinical trial. 2. Perforation of tympanic membrane or other tympanic membrane disorders that would interfere with the delivery and safety assessment of an intratympanic medication or reasonably be suspected to affect tympanic membrane healing after injection in study ear. This includes a current tympanostomy tube. 3. Any conductive hearing loss of greater than 15 dB at a single frequency or greater than 10dB at two or more contiguous octave frequencies in the study ear at the Screening visit. 4. Active chronic middle ear disease or a history of major middle ear surgery, as an adult, in the ear to be injected. 5. Subject has had an intratympanic injection in either ear within 3 months of the screening visit. 6. Evidence of or previous diagnosis of auditory neuropathy, traumatic brain injury, central hearing loss, or genetic hearing loss. 7. History of chronic, recurrent clinically significant vestibular symptoms. 8. History of bilateral sudden sensorineural hearing loss or recurrent sudden sensorineural hearing loss. 9. History of clinically significant systemic autoimmune disease (e.g. rheumatoid arthritis, Sjogren's syndrome, multiple sclerosis, psoriasis). 10. History of head or neck radiation, treatment, or exposure to platinum based chemotherapy drugs or aminoglycosides. 11. Exposure to another investigational drug within 28 days prior to screening visit. 12. Evidence of any active or chronic disease or condition that could interfere with, or for which the treatment of might interfere with, the conduct of the study, or that would pose an unacceptable risk to the subject in the opinion of the investigator following a detailed medical history, physical examination, and vital signs (systolic and diastolic blood pressure, pulse rate, body temperature). 13. Positive urine pregnancy test or breast-feeding. 14. Any known factor, condition, or disease that, in the view of the Investigator, might interfere with treatment compliance, study conduct or interpretation of the results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Word Recognition in Quiet | Baseline through Day 90 | Percent of subjects exceeding the Carney-Schlauch 95% confidence interval for improvement from baseline in number of words recognized from Consonant-Nucleus-Consonant (CNC) word lists |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Words-in-Noise | Baseline through Day 90 | Mean absolute percent change in number of recognized words from CNC word lists |
| Standard Pure Tone Audiometry | Baseline through Day 90 | Mean overall pure tone average (PTA) hearing thresholds in decibels (dB) derived by averaging the air conduction thresholds at 0.5, 1, 2 and 4 kHZ frequencies |
| Patient Global Impression of Change (PGI-C) Hearing Loss Scale | Day 90 | Average response in PGI-C hearing loss scale, using the assigned numeric values of 1-5: 1) much better, 2) a little better, 3) no change, 4) a little worse 5) much worse |
| Patient Global Impression of Change (PGI-C) Daily Impacts Scale | Day 90 | Average response in PGI-C daily impacts scale, using the assigned numeric values of 1-5: 1) much better, 2) a little better, 3) no change, 4) a little worse 5) much worse |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| FX-322 Single intratympanic injection of FX-322 (laduviglusib 0.628 mg/sodium valproate 17.72 mg) into affected ear | 68 |
| Placebo Single intratympanic injection of placebo into affected ear | 72 |
| Total | 140 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Missed visit 5/Day 60 visit | 1 | 1 |
Baseline characteristics
| Characteristic | FX-322 | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 52.9 Years STANDARD_DEVIATION 11.12 | 51.7 Years STANDARD_DEVIATION 11.7 | 50.6 Years STANDARD_DEVIATION 12.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 15 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 61 Participants | 124 Participants | 63 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 11 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) White | 60 Participants | 124 Participants | 64 Participants |
| Region of Enrollment United States | 68 participants | 140 participants | 72 participants |
| Sex: Female, Male Female | 16 Participants | 45 Participants | 29 Participants |
| Sex: Female, Male Male | 52 Participants | 95 Participants | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 70 | 0 / 72 |
| other Total, other adverse events | 41 / 70 | 44 / 72 |
| serious Total, serious adverse events | 1 / 70 | 1 / 72 |
Outcome results
Primary
Word Recognition in Quiet
Percent of subjects exceeding the Carney-Schlauch 95% confidence interval for improvement from baseline in number of words recognized from Consonant-Nucleus-Consonant (CNC) word lists
Time frame: Baseline through Day 90
Population: Full Analysis Set is defined as all randomized subjects that met inclusion criteria who received one dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FX-322 | Word Recognition in Quiet | 14.7 Percent of subjects |
| Placebo | Word Recognition in Quiet | 11.1 Percent of subjects |
p-value: 0.52595% CI: [0.51, 3.73]Chi-squared
p-value: 0.52595% CI: [-7.52, 14.71]Chi-squared
Secondary
Patient Global Impression of Change (PGI-C) Daily Impacts Scale
Average response in PGI-C daily impacts scale, using the assigned numeric values of 1-5: 1) much better, 2) a little better, 3) no change, 4) a little worse 5) much worse
Time frame: Day 90
Population: Full Analysis Set is defined as all randomized subjects that met inclusion criteria who received one dose of study drug
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FX-322 | Patient Global Impression of Change (PGI-C) Daily Impacts Scale | 3.0 Score on a scale | Standard Deviation 0.53 |
| Placebo | Patient Global Impression of Change (PGI-C) Daily Impacts Scale | 2.8 Score on a scale | Standard Deviation 0.6 |
p-value: 0.02795% CI: [0.03, 0.41]ANCOVA
Secondary
Patient Global Impression of Change (PGI-C) Hearing Loss Scale
Average response in PGI-C hearing loss scale, using the assigned numeric values of 1-5: 1) much better, 2) a little better, 3) no change, 4) a little worse 5) much worse
Time frame: Day 90
Population: Full Analysis Set is defined as all randomized subjects that met inclusion criteria who received one dose of study drug
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FX-322 | Patient Global Impression of Change (PGI-C) Hearing Loss Scale | 3.0 Score on a scale | Standard Deviation 0.52 |
| Placebo | Patient Global Impression of Change (PGI-C) Hearing Loss Scale | 2.9 Score on a scale | Standard Deviation 0.64 |
p-value: 0.1695% CI: [-0.06, 0.34]ANCOVA
Secondary
Standard Pure Tone Audiometry
Mean overall pure tone average (PTA) hearing thresholds in decibels (dB) derived by averaging the air conduction thresholds at 0.5, 1, 2 and 4 kHZ frequencies
Time frame: Baseline through Day 90
Population: Full Analysis Set is defined as all randomized subjects that met inclusion criteria who received one dose of study drug
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FX-322 | Standard Pure Tone Audiometry | 65.09 Decibels (dB) | Standard Deviation 7.865 |
| Placebo | Standard Pure Tone Audiometry | 63.91 Decibels (dB) | Standard Deviation 9.816 |
Secondary
Words-in-Noise
Mean absolute percent change in number of recognized words from CNC word lists
Time frame: Baseline through Day 90
Population: Full Analysis Set is defined as all randomized subjects that met inclusion criteria who received one dose of study drug
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FX-322 | Words-in-Noise | 0.17 Percent change | Standard Deviation 2.465 |
| Placebo | Words-in-Noise | 0.35 Percent change | Standard Deviation 3.295 |
p-value: 0.97395% CI: [-0.954, 0.987]Mixed Models Analysis