Fibroblast Growth Factor Regeneration of Tympanic Membrane Perforations

A Phase II randomized trial will be initiated to evaluate efficacy as the primary measureable
outcome. Eligible and consented patients will be randomized in a 3:1 ratio to the optimal
biologic dose (OBD) of FGF-2 or placebo (sterile water).

Application of the study treatment may occur at the initial Screening Visit (pending all
eligibility requirements can be confirmed) or at Visit 1 and may be repeated at each follow
up visit as needed for a maximum of three treatments per treatment arm. These follow up
visits will occur three weeks (+/- 7 days) from the last treatment application. During these
visits, the subject's tympanic membrane will be examined, photographed, and additional
otologic tests will be performed. If the perforation is found to be closed during these
visits, then the subject will report in 2 months (+/-7 days) for a final study visit.

If the subject's TMP has not closed after the third and final application of their assigned
treatment group, then the subject will be crossed over to the other treatment group. Again,
the subject may be given up to three additional treatments in this new group. The follow up
visits will follow the same schedule, occurring three weeks (+/- 7 days) from the last
treatment. The same otologic procedures will be performed as in the previous visits.

All subjects will report for a final study visit 2 months (+/- 7 days) after their last
follow up visit when the perforation is determined to be closed or when the subject has
completed the maximum number of study visits without perforation closure. The study will be
completed for reporting purposes after all subjects have completed the 2 month (+/- 7 days)
follow up final visit.

Inclusion Criteria:

1. Dry tympanic membrane perforation of greater than 3 months duration

2. If female, post-menopausal or sterile, or if she is of child-bearing potential, must
have a negative beta-human chorionic gonadotropin (HCG) test and must be using an
adequate form of birth control such as birth control pills, birth control implants,
intrauterine devices (IUDs), diaphragms or condoms.

Exclusion Criteria:

The presence of any of the following excludes a subject from study enrollment:

- 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

- 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 (See body of protocol for full list of exclusions)

- Known or suspected allergies to any components used in the study

- Subjects who have cholesteatoma mass 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