Fibroblast Growth Factor Regeneration of Tympanic Membrane Perforations

This study is a double blinded, placebo-controlled phase II study evaluating the efficacy of FGF-2 for the treatment of chronic non-healing tympanic membrane perforations (TMP). The documentation of TM closure will be the main efficacy outcome measure. Pretreatment photographs will document the area of the TM perforation and allow measurement of surface areas of the TMP for comparison of pre- and post-treatment. The study will be divided into two phases, the Randomized Treatment phase (part A), and the Unblinded Crossover phase (part B). In part A of the study, subjects will be randomized 1:1 (using simple randomization) to receive FGF-2 or placebo treatment up to 3 treatments. Subjects that fail three study treatments will move on to part B of the study. Subjects who received placebo in part A and failed three placebo treatments will crossover to receive unblinded FGF-2 for up to 3 treatments. Subjects who received FGF-2 in part A and failed three experimental treatments will not have additional FGF-2 treatment, and will move on to study follow up.

Study Overview

• Status: Completed
• Conditions: Tympanic Membrane Perforation
• Intervention / Treatment: Drug: Placebo; Drug: FGF-2

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18 years and older
• Dry tympanic membrane perforation of at least 6 months duration
• Any person of child-bearing potential, must have a negative beta-HCG test and must agree to use an adequate form of birth control throughout the clinical trial.

Exclusion Criteria:

• Active otitis media or chronic otorrhea from the middle ear
• Subjects receiving radiation therapy, corticosteroids, immunosuppressive agents, or chemotherapy
• Subjects who, at study entry, are taking systemic antibiotics
• Subjects who are immunosuppressed
• Subjects experiencing bacterial or viral infection or who may otherwise be febrile or may be with inflammation.
• Life expectancy of less than 1 year
• Active alcohol or drug abuse within 6 months prior to study entry
• Significant medical condition that could prevent full participation in the procedures required for the study
• Known or suspected allergies to any components used in the study, i.e. porcine collagen
• Subjects who have cholesteatoma mass, or endothelium invasion in the tympanic cavity
• Subjects whose total perforation cannot be seen by an endoscope
• Subjects with inadequately controlled diabetes mellitus (NGSP: HbA1c 6.9% or higher)
• Subjects with a history of malignant ear canal tumors within 3 years of screening for eligibility
• Subjects who have undergone prior myringoplasty or tympanoplasty
• Subjects whose TMP is a result of thermal burn, or radiation therapy.
• Subjects who have abnormalities in the auditory ossicles or their linkages
• Subjects having moderate to severe dementia such as Alzheimer's disease or senile dementia
• Subjects whose hearing ability does not improve to bone-conduction hearing on a hearing acuity test using the tentative closure of perforation with a wet cotton ball.
• Subject having residual TM with abnormal form or abnormal shape anatomically
• Subjects having any granulation or soft tissue density due to inflammation, or infection in mastoid antrum determined by CT scanning (Temporal bone CT scanning)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; FGF-2 will be replaced with sterile water to saturate a pledget of gelatin sponge. The method will be otherwise identical to the FGF-2 intervention.
Experimental: Human Fibroblast Growth Factor-2 (FGF-2)	Drug: FGF-2; The FGF-2 method of use comprises a pledget of gelatin sponge, with human fibroblast growth factor-2 (FGF-2) added to the pledget just before topical application to the tympanic membrane, and the use of fibrin glue used for applications in ear surgery. The concentration of the FGF-2 solution will be 100μg of FGF-2 per 1 mL with an estimated dose of about 20 μg in 0.2ml. Fibrin glue will be applied to secure gelatin sponge after placement according to the size of the membrane perforation. Application of the study treatment will occur at Visit 1 and may be repeated at each follow up visit as needed for a maximum of three treatments in the Randomized Treatment Phase (Visit 1, Visit 2, and Visit 3).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TMP Closure Ratio	Determined by otoscopic exam and photographic documentation	up to Day 134

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Closure of TMP		up to Day 134
Air-Bone Gap (ABG)	Defined as the difference between air-conduction and bone-conduction audiometric thresholds	up to Day 134
Mobility of the Tympanic Membrane	As measured by tympanometry	Day 134
Salvage Rate of FGF-2 in Patients who Fail Placebo		Day 64
Pure-tone and speech discrimination scores	Measured by audiograms (total range of score: 125, 250, 500, 1000, 2000, 4000, 8000 Hz).	Pre-treatment (Day 1)
Pure-tone and speech discrimination scores	Measured by audiograms (total range of score: 125, 250, 500, 1000, 2000, 4000, 8000 Hz).	Post-treatment 1 (Day 22)
Pure-tone and speech discrimination scores	Measured by audiograms (total range of score: 125, 250, 500, 1000, 2000, 4000, 8000 Hz).	Post-treatment 1 (Day 43)
Pure-tone and speech discrimination scores	Measured by audiograms (total range of score: 125, 250, 500, 1000, 2000, 4000, 8000 Hz).	Post-treatment 1 (Day 64)
Pure-tone and speech discrimination scores	Measured by audiograms (total range of score: 125, 250, 500, 1000, 2000, 4000, 8000 Hz).	Post-treatment 1 (Day 85)
Pure-tone and speech discrimination scores	Measured by audiograms (total range of score: 125, 250, 500, 1000, 2000, 4000, 8000 Hz).	Post-treatment 1 (Day 106)
Pure-tone and speech discrimination scores	Measured by audiograms (total range of score: 125, 250, 500, 1000, 2000, 4000, 8000 Hz).	Post-treatment 1 (Day 127)
Pure-tone and speech discrimination scores	Measured by audiograms (total range of score: 125, 250, 500, 1000, 2000, 4000, 8000 Hz).	Post-treatment 1 (Day 134)

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Investigators: Principal Investigator: David Friedmann, MD, NYU Langone Health

Study record dates

Study Major Dates

• Study Start (Actual): May 27, 2022
• Primary Completion (Actual): September 30, 2025
• Study Completion (Actual): October 27, 2025

Study Registration Dates

• First Submitted: July 2, 2021
• First Submitted That Met QC Criteria: July 2, 2021
• First Posted (Actual): July 13, 2021

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries; Otorhinolaryngologic Diseases; Ear Diseases; Tympanic Membrane Perforation; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Intercellular Signaling Peptides and Proteins; Fibroblast Growth Factors; Fibroblast Growth Factor 2
• Other Study ID Numbers: 21-00672

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Only aggregate data will be shared upon reasonable request.
• IPD Sharing Time Frame: Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
• IPD Sharing Access Criteria: The investigator who proposed to use the data will have access to the data upon reasonable request. Requests should be directed to David.friedmann@nyulangone.org. To gain access, data requestors will need to sign a data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

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