FX-322 in Adults With Severe Sensorineural Hearing Loss

A Phase 1b, Prospective, Randomized, Double-Blind, Placebo- Controlled, Single-Dose, Multicenter, Safety Study of FX-322 Administered by Intratympanic Injection in Adults With Severe Sensorineural Hearing Loss

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 severe sensorineural hearing loss.

Study Overview

• Status: Completed
• Conditions: Hearing Loss, Sensorineural; Noise Induced Hearing Loss; Sudden Hearing Loss
• Intervention / Treatment: Other: Placebo; Drug: FX-322

Detailed Description

This is a Phase 1b placebo-controlled, double-blind, single-dose safety study of intratympanic FX-322 dosed in subjects with severe 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 Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Novi, Michigan, United States, 00000
      • Clinical Trial Site
  • Nebraska
    • Omaha, Nebraska, United States, 00000
      • Clinical Trial Site
  • New York
    • Amherst, New York, United States, 00000
      • Clinical Trial Site
  • South Carolina
    • Orangeburg, South Carolina, United States, 00000
      • Clinical Trial Site
  • Texas
    • San Antonio, Texas, United States, 00000
      • Clinical Trial Site - San Antonio #1
    • San Antonio, Texas, United States, 00000
      • Clinical Trial Site - San Antonio #2
  • Virginia
    • Norfolk, Virginia, United States, 00000
      • Clinical Trial Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.
3. Documented medical history consistent with acquired (non-genetic) severe sensorineural hearing loss (documented audiogram at least 6 months prior to screening required).
4. A pure tone average of 71-90 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. 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 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).
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. History of clinically significant vestibular symptoms at the discretion of the investigator. For example, BPPV may be considered acceptable whereas Meniere's would not.
7. History of clinically significant systemic autoimmune disease (e.g. rheumatoid arthritis, Sjogren's syndrome, multiple sclerosis, psoriasis).
8. Exposure to another investigational drug within 28 days prior to injection of study drug.
9. 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).

10. 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. Male subjects should use condoms with spermicide during the study or remain abstinent. Subjects should not donate sperm or ova during the study period.

11. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: FX-322; FX-322, 1 dose (N=24)	Drug: FX-322; Active Comparator
Placebo Comparator: Placebo; Placebo, 1 dose (n=6)	Other: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systemic Safety: Number of patients with treatment-related adverse events	Number of patients with treatment-related adverse events assessed by CTCAE v5.0	3 months
Local Safety: Number of patients with abnormal changes from baseline in otoscopic examinations	Microscopic otoscopy will be included to specifically record any abnormalities of the external ear canal, tympanic membrane and middle ear.	3 months
Local Safety: The number of patients with abnormal changes from baseline in tympanometry	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.	3 months
Columbia-Suicide Severity Rating Scale (C-SSRS)	Risk assessment through a series of simple, plain-language questions	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Audiologic Response Endpoints: Speech Intelligibility - Word Recognition in Quiet (WR)	Assessment of speech intelligibility using the Word Recognition in Quiet test measured with Consonant-Nucleus-Consonant (CNC) word lists.	3 months
Standard Pure Tone Audiometry	Standard pure tone audiometry will be measured to determine a subject's threshold for hearing at standard frequencies (Hz)	3 months
Extended High Frequency Pure Tone Audiometry	Pure tone audiometry will be measured to determine a subject's threshold for hearing at extended high range frequencies (Hz)	3 months
Audiologic Response: Speech Intelligibility - Bamford-Kowal-Bench Speech in Noise (BKB-SIN)	Speech intelligibility using the BKB-SIN test measured with a list of sentences presented to the subject.	3 months
Tinnitus Assessment	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.	2 months

Collaborators and Investigators

• Sponsor: Frequency Therapeutics
• Investigators: Study Director: Carl LeBel, PhD, Frequency Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2020
• Primary Completion (Actual): May 26, 2021
• Study Completion (Actual): September 20, 2021

Study Registration Dates

• First Submitted: November 10, 2020
• First Submitted That Met QC Criteria: November 10, 2020
• First Posted (Actual): November 16, 2020

Study Record Updates

• Last Update Posted (Actual): February 1, 2022
• Last Update Submitted That Met QC Criteria: January 31, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Intratympanic administration; Restoration of hearing loss
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Otorhinolaryngologic Diseases; Ear Diseases; Sensation Disorders; Hearing Disorders; Hearing Loss; Deafness; Hearing Loss, Sensorineural; Hearing Loss, Noise-Induced; Hearing Loss, Sudden
• Other Study ID Numbers: FX-322-113

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No