FX-322 in Adults With Stable Sensorineural Hearing Loss

• ClinicalTrials.gov Identifier: NCT04120116
• Recruitment Status: Active, not recruiting
• First Posted: October 9, 2019
• Last Update Posted: October 8, 2020
• Sponsor: Frequency Therapeutics
• Information provided by (Responsible Party): Frequency Therapeutics

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Sensorineural Hearing Loss; Noise Induced Hearing Loss; Sudden Sensorineural Hearing Loss	Drug: FX-322; Drug: Placebo	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 95 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2a, Prospective, Randomized, Double-Blind, Placebo-Controlled, Single and Repeat-Dose, Multicenter, Exploratory Efficacy Study of FX-322 Administered by Intratympanic Injection in Adults With Stable Sensorineural Hearing Loss
• Actual Study Start Date: October 4, 2019
• Actual Primary Completion Date: October 6, 2020
• Estimated Study Completion Date: May 21, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: FX-322 Single Dose, Placebo Three Doses; Four intratympanic injections of a hydrogel formulation	Drug: FX-322; Dosing occurs once weekly for four consecutive weeks. Patients will receive one, two or four doses of FX-322, followed by three, two or zero Placebo doses, respectively.; Drug: Placebo; Dosing occurs once weekly for four consecutive weeks. Patients will receive two, three or four doses of Placebo, preceded by two, one or zero Placebo doses, respectively.
Experimental: FX-322 Two Doses, Placebo Two Doses; Four intratympanic injections of a hydrogel formulation	Drug: FX-322; Dosing occurs once weekly for four consecutive weeks. Patients will receive one, two or four doses of FX-322, followed by three, two or zero Placebo doses, respectively.; Drug: Placebo; Dosing occurs once weekly for four consecutive weeks. Patients will receive two, three or four doses of Placebo, preceded by two, one or zero Placebo doses, respectively.
Experimental: FX-322 Four Doses; Four intratympanic injections of a hydrogel formulation	Drug: FX-322; Dosing occurs once weekly for four consecutive weeks. Patients will receive one, two or four doses of FX-322, followed by three, two or zero Placebo doses, respectively.
Placebo Comparator: Placebo Four Doses; Four intratympanic injections of a hydrogel formulation	Drug: Placebo; Dosing occurs once weekly for four consecutive weeks. Patients will receive two, three or four doses of Placebo, preceded by two, one or zero Placebo doses, respectively.

Outcome Measures

Primary Outcome Measures :

1. Speech Intelligibility [ Time Frame: Screening to Day 210 ]
   Assessment of speech intelligibility using the Word Recognition in Quiet test measured with Consonant-Nucleus-Consonant (CNC) word lists.
2. Speech Intelligibility [ Time Frame: Screening to Day 210 ]
   Speech intelligibility using the Words-in-Noise test measured with Consonant-Nucleus-Consonant (CNC) word lists
3. Standard Pure Tone Audiometry [ Time Frame: Screening to Day 210 ]
   Standard pure tone audiometry will be measured to determine a subject's threshold for hearing at standard frequencies (Hz)
4. Systemic Safety: Number of patients with treatment-related adverse events [ Time Frame: Screening to Day 210 ]
   Number of patients with treatment-related adverse events assessed by CTCAE v5.0
5. Local Safety: Number of patients with abnormal changes from baseline in otoscopic examinations [ Time Frame: Screening to Day 210 ]
   Microscopic otoscopy will be included to specifically record any abnormalities of the external ear canal, tympanic membrane and middle ear.
6. Local Safety: The number of patients with abnormal changes from baseline in tympanometry [ Time Frame: Screening to Day 210 ]
   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 :

1. Extended High Frequency Pure Tone Audiometry [ Time Frame: Screening to Day 210 ]
   Pure tone audiometry will be measured to determine a subject's threshold for hearing at extended high range frequencies (Hz)
2. Tinnitus Assessment [ Time Frame: Screening to Day 210 ]
   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.
3. Hearing Handicap Inventory [ Time Frame: Screening to Day 210 ]
   The Hearing Handicap Inventory for Adults (HHIA), is a 25-item self-assessment scale composed of two subscales (emotional and social/situational). The subject will self-report one of the following answers for each item on the scale: Yes, Sometimes, No.
4. Hearing Screening Inventory [ Time Frame: Screening to Day 210 ]
   The Hearing Screening Inventory (HSI) is a 12 item self report inventory to assess hearing impairment. The subject will self report one of the following answers, for each question from 1 to 8: Never, Seldom, Occasionally, Frequently, Always, and for each question from 9 to 12: Good, Average, Slightly below average, Poor, Very Poor. The HSI is designed to assess subjective change during the study.

Eligibility Criteria

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

Criteria

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).

Contacts and Locations

Locations

United States, California

Clinical Trial Site

Fresno, California, United States, 93720

Clinical Trial Site

Torrance, California, United States, 90503

United States, Colorado

Clinical Trial Site

Colorado Springs, Colorado, United States, 80909

United States, Florida

Clinical Trial Site

Boca Raton, Florida, United States, 33487

Clinical Trial Site

Sarasota, Florida, United States, 34239

Clinical Trial Site

Tampa, Florida, United States, 33612

United States, Kentucky

Clinical Trial Site

Louisville, Kentucky, United States, 40207

United States, Nebraska

Clinical Trial Site

Omaha, Nebraska, United States, 68118

United States, New York

Clinical Trial Site

Amherst, New York, United States, 14226

United States, North Carolina

Clinical Trial Site

Matthews, North Carolina, United States, 28105

Clinical Trial Site

Winston-Salem, North Carolina, United States, 27103

United States, South Carolina

Clinical Trial Site

Orangeburg, South Carolina, United States, 29118

United States, Texas

Clinical Trial Site

Austin, Texas, United States, 78705

Clinical Trial Site

San Antonio, Texas, United States, 78240

Clinical Trial Site

San Antonio, Texas, United States, 78258

United States, Virginia

Clinical Trial Site

Richmond, Virginia, United States, 23235

Sponsors and Collaborators

Frequency Therapeutics

Investigators

• Study Director: Carl LeBel, PhD; Frequency Therapeutics

More Information

• Responsible Party: Frequency Therapeutics
• ClinicalTrials.gov Identifier: NCT04120116
• Other Study ID Numbers: FX-322-202
• First Posted: October 9, 2019
• Last Update Posted: October 8, 2020
• Last Verified: October 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Frequency Therapeutics:

Intratympanic Administration; Restoration of Hearing Function

Additional relevant MeSH terms:

Hearing Loss; Deafness; Hearing Loss, Sensorineural; Hearing Loss, Noise-Induced; Hearing Disorders; Ear Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases