Noise Induced Hearing Loss, Sensorineural Hearing Loss, Sudden Sensorineural Hearing Loss
Conditions
Keywords
Intratympanic Administration, Restoration of Hearing Function
Brief summary
This is a phase 2a single and repeat dose exploratory efficacy study of intratympanic FX-322 compared to placebo in healthy male and female adults with stable sensorineural hearing loss.
Detailed description
Sensorineural hearing loss (SNHL) accounts for about 90% of all cases of hearing loss. This phase 2a study will assess the exploratory efficacy, as well as the local and systemic safety of single and repeat intratympanic doses of FX-322 compared to placebo in approximately 96 subjects with stable mild to moderately severe sensorineural hearing loss, with a medical history consistent with either excessive noise exposure or idiopathic sudden sensorineural hearing loss.
Interventions
DRUGFX-322 (One Dose)
Patients will receive one dose of FX-322.
DRUGFX-322 (Two Doses)
Patients will receive two doses of FX-322.
DRUGFX-322 (Four Doses)
Patients will receive four doses of FX-322.
DRUGPlacebo
Patients will receive 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. Adults aged 18-65 years inclusive. 2. Established diagnosis of stable sensorineural hearing loss by standard audiometric measures for ≥ 6 months prior to the Screening visit (no changes in air conduction greater than 10 dB at a single frequency or greater than 5 dB at two contiguous frequencies from the prior audiogram to the Screening audiogram in the study ear). 3. Documented medical history consistent with hearing loss being caused by noise exposure or sudden sensorineural hearing loss. 4. Pure Tone Audiometry (PTA) within 26-70 dB in the ear to be injected. 5. 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 or an intrauterine device and condoms) 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.
Exclusion criteria
1. Previous participation in FX-322 clinical trial. 2. Currently on any medication consisting of valproic acid, valproate sodium, or divalproex sodium. 3. 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. 4. Any conductive hearing loss of greater than 15 dB at a single frequency or greater than 10 dB at two or more contiguous octave frequencies in the study ear at the Screening visit or on the prior audiogram (if the Investigator feels there is not a true conductive hearing loss, the Medical Monitor should be consulted). 5. Active chronic middle ear disease or a history of major middle ear surgery, as an adult, in the ear to be injected. 6. Subject has had an intratympanic injection in either ear within 6 months of the screening visit. 7. History of clinically significant vestibular symptoms at the discretion of the investigator. 8. History of clinically significant systemic autoimmune disease. 9. History of head or neck radiation treatment or exposure. 10. History of platinum-based chemotherapy treatment. 11. Exposure to another investigational drug within 28 days prior to injection of study drug. 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. History of substance abuse within 2 years of the Screening Visit. 14. Positive test for drugs of abuse at screening. 15. Positive urine pregnancy test or breast-feeding. 16. 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 (e.g. previous high-dose aminoglycoside treatment).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Word Recognition in Quiet | Baseline to Day 210 | 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 |
| Words-in-Noise | Baseline to Day 210 | Mean absolute percent change in number of recognized words from CNC word lists |
| Pure Tone Audiometry | Baseline to Day 210 | Mean overall pure tone average (PTA) hearing thresholds in decibels (dB) derived by averaging the air conduction thresholds at 0.5, 1, 2 and 4kHZ frequencies |
| Treatment-emergent Adverse Events (TEAEs) | Baseline to Day 210 | Number of patients with treatment-related adverse events assessed by CTCAE v5.0 |
| Otoscopy Abnormalities | Baseline and Days 8, 15, 21 60, 90,150, and 210 | Number of treated ears with abnormalities of the external ear canal, tympanic membrane and middle ear at each specified time point |
| Tympanometry Abnormalities | Baseline and Days 15, 60, 90, 150, 210 | Number of treated ears with changes in middle ear compliance (mL), peak pressure (daPa), and/or ear canal volume (mL) from baseline |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1: FX-322 Single Dose, Placebo Three Doses Four weekly intratympanic injections:
One dose of FX-322 (laduviglusib 0.628 mg/sodium valproate 17.72 mg) followed by three doses of placebo | 23 |
| Group 2: FX-322 Two Doses, Placebo Two Doses Four weekly intratympanic injections:
Two doses of FX-322 (laduviglusib 0.628 mg/sodium valproate 17.72 mg) followed by two doses of placebo | 25 |
| Group 3: FX-322 Four Doses Four weekly intratympanic injections of FX-322 (laduviglusib 0.628 mg/sodium valproate 17.72 mg) | 21 |
| Group 4: Placebo Four Doses Four weekly intratympanic injections of placebo | 21 |
| Total | 90 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 2 |
| Overall Study | Subject was deemed to not meet the inclusion criteria for SNHL after dose was administered | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Group 1: FX-322 Single Dose, Placebo Three Doses | Total | Group 4: Placebo Four Doses | Group 3: FX-322 Four Doses | Group 2: FX-322 Two Doses, Placebo Two Doses |
|---|---|---|---|---|---|
| Age, Continuous | 54.8 Years STANDARD_DEVIATION 8.93 | 53.9 Years STANDARD_DEVIATION 10.91 | 55.1 Years STANDARD_DEVIATION 10.52 | 51.0 Years STANDARD_DEVIATION 13.61 | 54.4 Years STANDARD_DEVIATION 10.58 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 10 Participants | 4 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants | 80 Participants | 17 Participants | 20 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 7 Participants | 2 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 19 Participants | 79 Participants | 18 Participants | 19 Participants | 23 Participants |
| Region of Enrollment United States | 23 participants | 90 participants | 21 participants | 21 participants | 25 participants |
| Sex: Female, Male Female | 8 Participants | 26 Participants | 7 Participants | 3 Participants | 8 Participants |
| Sex: Female, Male Male | 15 Participants | 64 Participants | 14 Participants | 18 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 25 | 0 / 21 | 0 / 23 | 0 / 95 |
| other Total, other adverse events | 16 / 24 | 16 / 25 | 19 / 21 | 12 / 23 | 64 / 95 |
| serious Total, serious adverse events | 0 / 24 | 0 / 25 | 0 / 21 | 0 / 23 | 1 / 95 |
Outcome results
Primary
Otoscopy Abnormalities
Number of treated ears with abnormalities of the external ear canal, tympanic membrane and middle ear at each specified time point
Time frame: Baseline and Days 8, 15, 21 60, 90,150, and 210
Population: Safety Analysis Set (SAS) is defined as all subjects exposed to study drug or placebo. For otoscopies, subjects were analyzed per the treatment group that reflected the number of FX-322 doses actually administered. Two subjects who were initially randomized to Group 3 only received 3 of the 4 doses of FX-322 and were analyzed in the FX-322 Pooled Group only. One subject who was initially randomized into Group 3 only received 1 of the 4 doses of FX-322 and therefore was analyzed in Group 1.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1: FX-322 Single Dose, Placebo Three Doses | Otoscopy Abnormalities | External - Day 8 | 1 Number of ears |
| Group 1: FX-322 Single Dose, Placebo Three Doses | Otoscopy Abnormalities | Middle Ear - Day 8 | 1 Number of ears |
| Group 1: FX-322 Single Dose, Placebo Three Doses | Otoscopy Abnormalities | Tympanic membrane - Baseline | 1 Number of ears |
| Group 1: FX-322 Single Dose, Placebo Three Doses | Otoscopy Abnormalities | External - Day 210 | 1 Number of ears |
| Group 1: FX-322 Single Dose, Placebo Three Doses | Otoscopy Abnormalities | External - Day 21 | 1 Number of ears |
| Group 1: FX-322 Single Dose, Placebo Three Doses | Otoscopy Abnormalities | External - Day 15 | 2 Number of ears |
| Group 1: FX-322 Single Dose, Placebo Three Doses | Otoscopy Abnormalities | External - Day 150 | 1 Number of ears |
| Group 1: FX-322 Single Dose, Placebo Three Doses | Otoscopy Abnormalities | Middle Ear - Day 15 | 1 Number of ears |
| Group 1: FX-322 Single Dose, Placebo Three Doses | Otoscopy Abnormalities | External - Day 60 | 0 Number of ears |
| Group 1: FX-322 Single Dose, Placebo Three Doses | Otoscopy Abnormalities | Middle Ear - Day 90 | 0 Number of ears |
| Group 1: FX-322 Single Dose, Placebo Three Doses | Otoscopy Abnormalities | External - Baseline | 0 Number of ears |
| Group 1: FX-322 Single Dose, Placebo Three Doses | Otoscopy Abnormalities | Middle Ear - Baseline | 0 Number of ears |
| Group 1: FX-322 Single Dose, Placebo Three Doses | Otoscopy Abnormalities | Tympanic membrane - 210 | 0 Number of ears |
| Group 1: FX-322 Single Dose, Placebo Three Doses | Otoscopy Abnormalities | Tympanic membrane - Day 150 | 1 Number of ears |
| Group 1: FX-322 Single Dose, Placebo Three Doses | Otoscopy Abnormalities | Middle Ear - Day 150 | 0 Number of ears |
| Group 1: FX-322 Single Dose, Placebo Three Doses | Otoscopy Abnormalities | Middle Ear - Day 60 | 0 Number of ears |
| Group 1: FX-322 Single Dose, Placebo Three Doses | Otoscopy Abnormalities | Tympanic membrane - Day 90 | 0 Number of ears |
| Group 1: FX-322 Single Dose, Placebo Three Doses | Otoscopy Abnormalities | Tympanic membrane - Day 60 | 0 Number of ears |
| Group 1: FX-322 Single Dose, Placebo Three Doses | Otoscopy Abnormalities | External - Day 90 | 0 Number of ears |
| Group 1: FX-322 Single Dose, Placebo Three Doses | Otoscopy Abnormalities | Middle Ear - Day 210 | 0 Number of ears |
| Group 1: FX-322 Single Dose, Placebo Three Doses | Otoscopy Abnormalities | Middle Ear - Day 21 | 1 Number of ears |
| Group 1: FX-322 Single Dose, Placebo Three Doses | Otoscopy Abnormalities | Tympanic membrane - Day 21 | 2 Number of ears |
| Group 1: FX-322 Single Dose, Placebo Three Doses | Otoscopy Abnormalities | Tympanic membrane - Day 15 | 4 Number of ears |
| Group 1: FX-322 Single Dose, Placebo Three Doses | Otoscopy Abnormalities | Tympanic membrane - Day 8 | 2 Number of ears |
| Group 2: FX-322 Two Doses, Placebo Two Doses | Otoscopy Abnormalities | Tympanic membrane - Day 150 | 0 Number of ears |
| Group 2: FX-322 Two Doses, Placebo Two Doses | Otoscopy Abnormalities | Middle Ear - Day 60 | 0 Number of ears |
| Group 2: FX-322 Two Doses, Placebo Two Doses | Otoscopy Abnormalities | External - Baseline | 0 Number of ears |
| Group 2: FX-322 Two Doses, Placebo Two Doses | Otoscopy Abnormalities | Middle Ear - Day 90 | 0 Number of ears |
| Group 2: FX-322 Two Doses, Placebo Two Doses | Otoscopy Abnormalities | Middle Ear - Day 150 | 0 Number of ears |
| Group 2: FX-322 Two Doses, Placebo Two Doses | Otoscopy Abnormalities | Middle Ear - Day 210 | 0 Number of ears |
| Group 2: FX-322 Two Doses, Placebo Two Doses | Otoscopy Abnormalities | External - Day 8 | 0 Number of ears |
| Group 2: FX-322 Two Doses, Placebo Two Doses | Otoscopy Abnormalities | External - Day 15 | 0 Number of ears |
| Group 2: FX-322 Two Doses, Placebo Two Doses | Otoscopy Abnormalities | External - Day 150 | 1 Number of ears |
| Group 2: FX-322 Two Doses, Placebo Two Doses | Otoscopy Abnormalities | External - Day 210 | 0 Number of ears |
| Group 2: FX-322 Two Doses, Placebo Two Doses | Otoscopy Abnormalities | External - Day 60 | 0 Number of ears |
| Group 2: FX-322 Two Doses, Placebo Two Doses | Otoscopy Abnormalities | Tympanic membrane - Baseline | 0 Number of ears |
| Group 2: FX-322 Two Doses, Placebo Two Doses | Otoscopy Abnormalities | Tympanic membrane - Day 8 | 3 Number of ears |
| Group 2: FX-322 Two Doses, Placebo Two Doses | Otoscopy Abnormalities | Tympanic membrane - Day 15 | 1 Number of ears |
| Group 2: FX-322 Two Doses, Placebo Two Doses | Otoscopy Abnormalities | External - Day 21 | 0 Number of ears |
| Group 2: FX-322 Two Doses, Placebo Two Doses | Otoscopy Abnormalities | Tympanic membrane - Day 21 | 1 Number of ears |
| Group 2: FX-322 Two Doses, Placebo Two Doses | Otoscopy Abnormalities | Tympanic membrane - Day 60 | 1 Number of ears |
| Group 2: FX-322 Two Doses, Placebo Two Doses | Otoscopy Abnormalities | External - Day 90 | 2 Number of ears |
| Group 2: FX-322 Two Doses, Placebo Two Doses | Otoscopy Abnormalities | Tympanic membrane - Day 90 | 1 Number of ears |
| Group 2: FX-322 Two Doses, Placebo Two Doses | Otoscopy Abnormalities | Middle Ear - Day 21 | 0 Number of ears |
| Group 2: FX-322 Two Doses, Placebo Two Doses | Otoscopy Abnormalities | Tympanic membrane - 210 | 0 Number of ears |
| Group 2: FX-322 Two Doses, Placebo Two Doses | Otoscopy Abnormalities | Middle Ear - Baseline | 0 Number of ears |
| Group 2: FX-322 Two Doses, Placebo Two Doses | Otoscopy Abnormalities | Middle Ear - Day 8 | 0 Number of ears |
| Group 2: FX-322 Two Doses, Placebo Two Doses | Otoscopy Abnormalities | Middle Ear - Day 15 | 0 Number of ears |
| Group 3: FX-322 Four Doses | Otoscopy Abnormalities | Tympanic membrane - Day 150 | 0 Number of ears |
| Group 3: FX-322 Four Doses | Otoscopy Abnormalities | Middle Ear - Day 210 | 0 Number of ears |
| Group 3: FX-322 Four Doses | Otoscopy Abnormalities | Middle Ear - Day 8 | 0 Number of ears |
| Group 3: FX-322 Four Doses | Otoscopy Abnormalities | Tympanic membrane - Day 60 | 0 Number of ears |
| Group 3: FX-322 Four Doses | Otoscopy Abnormalities | Middle Ear - Day 15 | 1 Number of ears |
| Group 3: FX-322 Four Doses | Otoscopy Abnormalities | Tympanic membrane - 210 | 0 Number of ears |
| Group 3: FX-322 Four Doses | Otoscopy Abnormalities | Tympanic membrane - Day 21 | 3 Number of ears |
| Group 3: FX-322 Four Doses | Otoscopy Abnormalities | External - Day 21 | 2 Number of ears |
| Group 3: FX-322 Four Doses | Otoscopy Abnormalities | Middle Ear - Day 90 | 0 Number of ears |
| Group 3: FX-322 Four Doses | Otoscopy Abnormalities | External - Day 15 | 1 Number of ears |
| Group 3: FX-322 Four Doses | Otoscopy Abnormalities | External - Day 150 | 1 Number of ears |
| Group 3: FX-322 Four Doses | Otoscopy Abnormalities | Middle Ear - Day 150 | 0 Number of ears |
| Group 3: FX-322 Four Doses | Otoscopy Abnormalities | Middle Ear - Day 60 | 0 Number of ears |
| Group 3: FX-322 Four Doses | Otoscopy Abnormalities | External - Day 210 | 1 Number of ears |
| Group 3: FX-322 Four Doses | Otoscopy Abnormalities | Tympanic membrane - Day 90 | 0 Number of ears |
| Group 3: FX-322 Four Doses | Otoscopy Abnormalities | Middle Ear - Baseline | 0 Number of ears |
| Group 3: FX-322 Four Doses | Otoscopy Abnormalities | External - Day 8 | 1 Number of ears |
| Group 3: FX-322 Four Doses | Otoscopy Abnormalities | Tympanic membrane - Day 15 | 2 Number of ears |
| Group 3: FX-322 Four Doses | Otoscopy Abnormalities | Tympanic membrane - Baseline | 0 Number of ears |
| Group 3: FX-322 Four Doses | Otoscopy Abnormalities | External - Day 90 | 0 Number of ears |
| Group 3: FX-322 Four Doses | Otoscopy Abnormalities | External - Day 60 | 0 Number of ears |
| Group 3: FX-322 Four Doses | Otoscopy Abnormalities | External - Baseline | 1 Number of ears |
| Group 3: FX-322 Four Doses | Otoscopy Abnormalities | Middle Ear - Day 21 | 1 Number of ears |
| Group 3: FX-322 Four Doses | Otoscopy Abnormalities | Tympanic membrane - Day 8 | 1 Number of ears |
| FX-322 Pooled | Otoscopy Abnormalities | Middle Ear - Baseline | 0 Number of ears |
| FX-322 Pooled | Otoscopy Abnormalities | External - Day 60 | 0 Number of ears |
| FX-322 Pooled | Otoscopy Abnormalities | Middle Ear - Day 210 | 0 Number of ears |
| FX-322 Pooled | Otoscopy Abnormalities | Tympanic membrane - Day 15 | 7 Number of ears |
| FX-322 Pooled | Otoscopy Abnormalities | External - Day 15 | 3 Number of ears |
| FX-322 Pooled | Otoscopy Abnormalities | Tympanic membrane - Day 21 | 6 Number of ears |
| FX-322 Pooled | Otoscopy Abnormalities | External - Baseline | 1 Number of ears |
| FX-322 Pooled | Otoscopy Abnormalities | Middle Ear - Day 150 | 0 Number of ears |
| FX-322 Pooled | Otoscopy Abnormalities | Middle Ear - Day 8 | 1 Number of ears |
| FX-322 Pooled | Otoscopy Abnormalities | Tympanic membrane - Day 60 | 1 Number of ears |
| FX-322 Pooled | Otoscopy Abnormalities | Middle Ear - Day 21 | 2 Number of ears |
| FX-322 Pooled | Otoscopy Abnormalities | Tympanic membrane - Day 90 | 1 Number of ears |
| FX-322 Pooled | Otoscopy Abnormalities | Tympanic membrane - Day 150 | 1 Number of ears |
| FX-322 Pooled | Otoscopy Abnormalities | External - Day 90 | 2 Number of ears |
| FX-322 Pooled | Otoscopy Abnormalities | Middle Ear - Day 90 | 0 Number of ears |
| FX-322 Pooled | Otoscopy Abnormalities | Tympanic membrane - 210 | 0 Number of ears |
| FX-322 Pooled | Otoscopy Abnormalities | External - Day 150 | 3 Number of ears |
| FX-322 Pooled | Otoscopy Abnormalities | External - Day 8 | 2 Number of ears |
| FX-322 Pooled | Otoscopy Abnormalities | Middle Ear - Day 15 | 2 Number of ears |
| FX-322 Pooled | Otoscopy Abnormalities | External - Day 210 | 2 Number of ears |
| FX-322 Pooled | Otoscopy Abnormalities | Tympanic membrane - Day 8 | 7 Number of ears |
| FX-322 Pooled | Otoscopy Abnormalities | Tympanic membrane - Baseline | 1 Number of ears |
| FX-322 Pooled | Otoscopy Abnormalities | External - Day 21 | 3 Number of ears |
| FX-322 Pooled | Otoscopy Abnormalities | Middle Ear - Day 60 | 0 Number of ears |
| Group 4: Placebo Four Doses | Otoscopy Abnormalities | Middle Ear - Day 210 | 0 Number of ears |
| Group 4: Placebo Four Doses | Otoscopy Abnormalities | External - Day 21 | 0 Number of ears |
| Group 4: Placebo Four Doses | Otoscopy Abnormalities | External - Day 60 | 0 Number of ears |
| Group 4: Placebo Four Doses | Otoscopy Abnormalities | External - Day 90 | 2 Number of ears |
| Group 4: Placebo Four Doses | Otoscopy Abnormalities | External - Baseline | 0 Number of ears |
| Group 4: Placebo Four Doses | Otoscopy Abnormalities | External - Day 8 | 1 Number of ears |
| Group 4: Placebo Four Doses | Otoscopy Abnormalities | External - Day 150 | 1 Number of ears |
| Group 4: Placebo Four Doses | Otoscopy Abnormalities | External - Day 210 | 1 Number of ears |
| Group 4: Placebo Four Doses | Otoscopy Abnormalities | Tympanic membrane - Baseline | 1 Number of ears |
| Group 4: Placebo Four Doses | Otoscopy Abnormalities | Tympanic membrane - Day 8 | 2 Number of ears |
| Group 4: Placebo Four Doses | Otoscopy Abnormalities | Tympanic membrane - Day 15 | 4 Number of ears |
| Group 4: Placebo Four Doses | Otoscopy Abnormalities | Tympanic membrane - Day 21 | 1 Number of ears |
| Group 4: Placebo Four Doses | Otoscopy Abnormalities | Tympanic membrane - Day 60 | 2 Number of ears |
| Group 4: Placebo Four Doses | Otoscopy Abnormalities | Tympanic membrane - Day 90 | 2 Number of ears |
| Group 4: Placebo Four Doses | Otoscopy Abnormalities | Tympanic membrane - Day 150 | 0 Number of ears |
| Group 4: Placebo Four Doses | Otoscopy Abnormalities | Tympanic membrane - 210 | 1 Number of ears |
| Group 4: Placebo Four Doses | Otoscopy Abnormalities | Middle Ear - Baseline | 0 Number of ears |
| Group 4: Placebo Four Doses | Otoscopy Abnormalities | Middle Ear - Day 8 | 0 Number of ears |
| Group 4: Placebo Four Doses | Otoscopy Abnormalities | Middle Ear - Day 15 | 1 Number of ears |
| Group 4: Placebo Four Doses | Otoscopy Abnormalities | Middle Ear - Day 21 | 1 Number of ears |
| Group 4: Placebo Four Doses | Otoscopy Abnormalities | Middle Ear - Day 60 | 0 Number of ears |
| Group 4: Placebo Four Doses | Otoscopy Abnormalities | Middle Ear - Day 90 | 0 Number of ears |
| Group 4: Placebo Four Doses | Otoscopy Abnormalities | Middle Ear - Day 150 | 0 Number of ears |
| Group 4: Placebo Four Doses | Otoscopy Abnormalities | External - Day 15 | 0 Number of ears |
Primary
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 4kHZ frequencies
Time frame: Baseline to Day 210
Population: Full Analysis Set is defined as all randomized subjects who received at least one dose of study drug or placebo in the study ear per the randomized treatment schedule. Only data from subjects in the FAS that attended the Day 210 visit were analyzed for this endpoint. FX-322 Pooled Group consists of subjects in the Groups 1, 2, and 3 combined. The Pooled Group is for analysis only and does not signify a separate randomized group of subjects.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Group 1: FX-322 Single Dose, Placebo Three Doses | Pure Tone Audiometry | 54.92 Decibels (dB) | Standard Error 2.284 |
| Group 2: FX-322 Two Doses, Placebo Two Doses | Pure Tone Audiometry | 55.08 Decibels (dB) | Standard Error 2.175 |
| Group 3: FX-322 Four Doses | Pure Tone Audiometry | 52.44 Decibels (dB) | Standard Error 2.372 |
| FX-322 Pooled | Pure Tone Audiometry | 54.15 Decibels (dB) | Standard Error 1.417 |
| Group 4: Placebo Four Doses | Pure Tone Audiometry | 52.90 Decibels (dB) | Standard Error 2.404 |
p-value: 0.63495% CI: [-3.945, 6.439]Mixed Models Analysis
Primary
Treatment-emergent Adverse Events (TEAEs)
Number of patients with treatment-related adverse events assessed by CTCAE v5.0
Time frame: Baseline to Day 210
Population: Safety Analysis Set (SAS) is defined as all subjects exposed to study drug or placebo. For TEAEs, subjects were analyzed per the treatment group that reflected the number of FX-322 doses actually administered. Two subjects who were initially randomized to Group 3 only received 3 of the 4 doses of FX-322 and were analyzed for TEAEs in the Total Group only. One subject who was initially randomized into Group 3 only received 1 of the 4 doses of FX-322 and therefore was analyzed in Group 1.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1: FX-322 Single Dose, Placebo Three Doses | Treatment-emergent Adverse Events (TEAEs) | 16 Participants |
| Group 2: FX-322 Two Doses, Placebo Two Doses | Treatment-emergent Adverse Events (TEAEs) | 16 Participants |
| Group 3: FX-322 Four Doses | Treatment-emergent Adverse Events (TEAEs) | 19 Participants |
| FX-322 Pooled | Treatment-emergent Adverse Events (TEAEs) | 12 Participants |
| Group 4: Placebo Four Doses | Treatment-emergent Adverse Events (TEAEs) | 64 Participants |
Primary
Tympanometry Abnormalities
Number of treated ears with changes in middle ear compliance (mL), peak pressure (daPa), and/or ear canal volume (mL) from baseline
Time frame: Baseline and Days 15, 60, 90, 150, 210
Population: Safety Analysis Set (SAS) is defined as all subjects exposed to study drug or placebo. For tympanometry tests, subjects were analyzed per the treatment group that reflected the number of FX-322 doses actually administered. Two subjects who were initially randomized to Group 3 only received 3 of the 4 doses of FX-322 and were analyzed in the FX-322 Pooled Group only. One subject who was initially randomized into Group 3 only received 1 of the 4 doses of FX-322 and thus was analyzed in Group 1
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1: FX-322 Single Dose, Placebo Three Doses | Tympanometry Abnormalities | Baseline | 0 Number of ears |
| Group 1: FX-322 Single Dose, Placebo Three Doses | Tympanometry Abnormalities | Day 15 | 2 Number of ears |
| Group 1: FX-322 Single Dose, Placebo Three Doses | Tympanometry Abnormalities | Day 60 | 0 Number of ears |
| Group 1: FX-322 Single Dose, Placebo Three Doses | Tympanometry Abnormalities | Day 90 | 0 Number of ears |
| Group 1: FX-322 Single Dose, Placebo Three Doses | Tympanometry Abnormalities | Day 150 | 0 Number of ears |
| Group 1: FX-322 Single Dose, Placebo Three Doses | Tympanometry Abnormalities | Day 210 | 0 Number of ears |
| Group 2: FX-322 Two Doses, Placebo Two Doses | Tympanometry Abnormalities | Day 150 | 0 Number of ears |
| Group 2: FX-322 Two Doses, Placebo Two Doses | Tympanometry Abnormalities | Day 210 | 0 Number of ears |
| Group 2: FX-322 Two Doses, Placebo Two Doses | Tympanometry Abnormalities | Baseline | 0 Number of ears |
| Group 2: FX-322 Two Doses, Placebo Two Doses | Tympanometry Abnormalities | Day 60 | 0 Number of ears |
| Group 2: FX-322 Two Doses, Placebo Two Doses | Tympanometry Abnormalities | Day 90 | 0 Number of ears |
| Group 2: FX-322 Two Doses, Placebo Two Doses | Tympanometry Abnormalities | Day 15 | 0 Number of ears |
| Group 3: FX-322 Four Doses | Tympanometry Abnormalities | Day 90 | 0 Number of ears |
| Group 3: FX-322 Four Doses | Tympanometry Abnormalities | Day 150 | 0 Number of ears |
| Group 3: FX-322 Four Doses | Tympanometry Abnormalities | Baseline | 1 Number of ears |
| Group 3: FX-322 Four Doses | Tympanometry Abnormalities | Day 60 | 0 Number of ears |
| Group 3: FX-322 Four Doses | Tympanometry Abnormalities | Day 15 | 4 Number of ears |
| Group 3: FX-322 Four Doses | Tympanometry Abnormalities | Day 210 | 1 Number of ears |
| FX-322 Pooled | Tympanometry Abnormalities | Day 90 | 0 Number of ears |
| FX-322 Pooled | Tympanometry Abnormalities | Day 15 | 6 Number of ears |
| FX-322 Pooled | Tympanometry Abnormalities | Day 60 | 0 Number of ears |
| FX-322 Pooled | Tympanometry Abnormalities | Day 210 | 1 Number of ears |
| FX-322 Pooled | Tympanometry Abnormalities | Day 150 | 0 Number of ears |
| FX-322 Pooled | Tympanometry Abnormalities | Baseline | 1 Number of ears |
| Group 4: Placebo Four Doses | Tympanometry Abnormalities | Day 150 | 0 Number of ears |
| Group 4: Placebo Four Doses | Tympanometry Abnormalities | Day 60 | 0 Number of ears |
| Group 4: Placebo Four Doses | Tympanometry Abnormalities | Day 15 | 4 Number of ears |
| Group 4: Placebo Four Doses | Tympanometry Abnormalities | Day 210 | 0 Number of ears |
| Group 4: Placebo Four Doses | Tympanometry Abnormalities | Day 90 | 0 Number of ears |
| Group 4: Placebo Four Doses | Tympanometry Abnormalities | Baseline | 2 Number of ears |
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 to Day 210
Population: Full Analysis Set is defined as all randomized subjects who received at least one dose of study drug or placebo in the study ear per the randomized treatment schedule. Only data from subjects in the FAS that attended the Day 210 visit were analyzed for this endpoint. The FX-322 Pooled Group consists of subjects in the Groups 1, 2, and 3 combined. The Pooled Group is for analysis only and does not signify a separate randomized group of subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1: FX-322 Single Dose, Placebo Three Doses | Word Recognition in Quiet | 23.8 Percent |
| Group 2: FX-322 Two Doses, Placebo Two Doses | Word Recognition in Quiet | 16.7 Percent |
| Group 3: FX-322 Four Doses | Word Recognition in Quiet | 15.8 Percent |
| FX-322 Pooled | Word Recognition in Quiet | 18.8 Percent |
| Group 4: Placebo Four Doses | Word Recognition in Quiet | 41.2 Percent |
p-value: 0.06895% CI: [0.11, 1.08]Mixed Models Analysis
Primary
Words-in-Noise
Mean absolute percent change in number of recognized words from CNC word lists
Time frame: Baseline to Day 210
Population: Full Analysis Set is defined as all randomized subjects who received at least one dose of study drug or placebo in the study ear per the randomized treatment schedule. Only data from subjects in the FAS that attended the Day 210 visit were analyzed for this endpoint. The FX-322 Pooled Group consists of subjects in the Groups 1, 2, and 3 combined. The Pooled Group is for analysis only and does not signify a separate randomized group of subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: FX-322 Single Dose, Placebo Three Doses | Words-in-Noise | 2.58 Percent change | Standard Deviation 7.251 |
| Group 2: FX-322 Two Doses, Placebo Two Doses | Words-in-Noise | 3.33 Percent change | Standard Deviation 8.933 |
| Group 3: FX-322 Four Doses | Words-in-Noise | 1.80 Percent change | Standard Deviation 7.236 |
| FX-322 Pooled | Words-in-Noise | 2.63 Percent change | Standard Deviation 7.822 |
| Group 4: Placebo Four Doses | Words-in-Noise | 3.61 Percent change | Standard Deviation 11.259 |