FX-322 in Adults With Age-Related Sensorineural Hearing Loss

Phase 1

Completed

• Conditions: Presbycusis; Noise Induced Hearing Loss; Sudden Hearing Loss; Hearing Loss, Sensorineural
• Interventions: Drug: FX-322; Other: placebo

• Registration Number: NCT04601909
• Lead Sponsor: Frequency Therapeutics

Brief Summary

This is a Phase 1b, prospective, randomized, double-blind, placebo-controlled, single-dose, multicenter, safety study of FX-322, administered by intratympanic injection, in adults with age-related sensorineural hearing loss.

Detailed Description

This is a Phase 1b placebo-controlled, double-blind, randomized, single-dose safety study of intratympanic FX-322 dosed in subjects with age-related sensorineural hearing loss.

Approximately 30 subjects are planned to be enrolled in this study. The subjects will be randomized to receive one dose FX-322 (24) or placebo (6) and will return for safety, otologic, and audiologic assessments at Days 30 and 90 after the study injection.

Study Timeline

• Study Start: 2020-09-17
• Study First Submitted: 2020-10-12
• Study First Submitted QC: 2020-10-20
• Study First Posted: 2020-10-26
• Status Verified: 2022-05
• Primary Completion: 2022-05-16
• Study Completion: 2022-05-16
• Last Update Submitted: 2022-05-24
• Last Update Posted: 2022-05-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

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 66-85 years inclusive.
3. Documented medical history consistent with age-related sensorineural hearing loss (documented audiogram at least 6 months prior to screening required).
4. A pure tone average of 26-70 dB at 500Hz, 1000Hz, 2000Hz, and 4000Hz at Screening 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.

Exclusion Criteria

1. Subject has previously participated in a FX-322 clinical trial.

2. Any subject with a flat audiogram between 500Hz and 8000Hz at Screening in the study ear. The difference in the range of threshold values across frequencies is ≤15 dB for the definition of a flat audiogram.

3. Clinically significant abnormalities on safety laboratory tests.

4. 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.

5. 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).

6. Active chronic middle ear disease or a history of major middle ear surgery, as an adult, in the ear to be injected.

7. Subject has had an intratympanic injection in either ear within 3 months of the screening visit.

8. History of clinically significant vestibular symptoms at the discretion of the investigator. For example, BPPV may be considered acceptable whereas Meniere's would not.

9. History of clinically significant systemic autoimmune disease (e.g. rheumatoid arthritis, Sjogren's syndrome, multiple sclerosis, psoriasis).

10. Exposure to another investigational drug within 28 days prior to injection of study drug.

11. 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).

12. Females of childbearing potential (those who are not surgically sterilized or post-menopausal) may not participate in the study if any of the following conditions exist:

    • Pregnant or intend to become pregnant
    • Nursing (lactating)
    • Does not agree to use adequate birth control methods for the duration of the study (adequate birth control methods are: hormonal- oral, implantable, transdermal or injectable contraceptives; mechanical- spermicide in conjunction with a barrier such as a condom or diaphragm, IUD, or surgical sterilization of a partner.

    NOTE: all female subjects of childbearing potential must consent to a urine pregnancy test as described in the Schedule of Assessments

13. 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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
FX-322	FX-322	FX-322, 1 dose (N=24)
Placebo	placebo	Placebo, 1 dose (n=6)

Primary Outcome Measures

Name	Time	Method
Local Safety: Number of patients with abnormal changes from baseline in otoscopic examinations	3 months	Microscopic otoscopy will be included to specifically record any abnormalities of the external ear canal, tympanic membrane and middle ear.
Columbia-Suicide Severity Rating Scale (C-SSRS)	3 months	Risk assessment through a series of simple, plain-language questions
Systemic Safety: Number of patients with treatment-related adverse events	3 months	Number of patients with treatment-related adverse events assessed by CTCAE v5.0
Local Safety: The number of patients with abnormal changes from baseline in tympanometry	3 months	Tympanometry tests the integrity of the tympanic membrane by varying air pressure in the ear canal. Middle ear compliance (mL), peak pressure (daPa), and ear canal volume (mL) will be recorded.

Secondary Outcome Measures

Name	Time	Method
Audiologic Response Endpoints: Speech Intelligibility - Word Recognition in Quiet (WR)	3 months	Assessment of speech intelligibility using the Word Recognition in Quiet test measured with Consonant-Nucleus-Consonant (CNC) word lists.
Standard Pure Tone Audiometry	3 months	Standard pure tone audiometry will be measured to determine a subject's threshold for hearing at standard frequencies (Hz)
Audiologic Response Endpoints: Speech Intelligibility - Words-In-Noise (WIN)	3 months	Speech intelligibility using the Words-in-Noise test measured with Consonant-Nucleus-Consonant (CNC) word lists
Tinnitus Assessment	3 months	Measured by the Tinnitus Functional Index (TFI), with a scale ranging from 0 to 100 that defines severity categories based on 25 self-reported answers.
Extended High Frequency Pure Tone Audiometry	3 months	Pure tone audiometry will be measured to determine a subject's threshold for hearing at extended high range frequencies (Hz)

Trial Locations

Locations (1)

Clinical Trial Site; 🇺🇸 Norfolk, Virginia, United States