Evaluation of Efficacy of 20 µg/ml rhNGF New Formulation (With Anti-oxidant) in Patients With Stage 2 and 3 NK

An 8-week phase II, multicenter, randomized, double-masked, vehicle-controlled, parallel
group study with a 24 or 32 week follow-up period to evaluate the efficacy of a formulation
containing anti-oxidant of recombinant human nerve growth factor (rhNGF) in 20 μg/ml, eye
drops solution versus vehicle containing anti-oxidant in patients with Stage 2 and 3
Neurotrophic Keratitis. The primary objective was to evaluate the efficacy of 20 μg/ml 6
times a day of recombinant human nerve growth factor (rhNGF) containing anti-oxidant, eye
drops solution compared to vehicle (formulation containing anti-oxidant) given 6 times a day
in inducing a complete healing of stage 2 (PED) and 3 (corneal ulcer) NK as measured by the
central reading center, evaluating the clinical pictures of corneal fluorescein staining.

Secondary objectives were to assess the duration of complete healing, improvement in visual
acuity and improvement in corneal sensitivity, and percentage of patients achieving complete
corneal clearing defined as complete absence of staining on the modified Oxford Scale.

Inclusion Criteria:

- Patients 18 years of age or older.

- Patients with stage 2 (persistent epithelial defect, PED) or stage 3 (corneal ulcer)
neurotrophic keratitis.

- PED or corneal ulceration of at least 2 weeks duration refractory to one or more
conventional non-surgical treatments for neurotrophic keratitis.

- Evidence of decreased corneal sensitivity (≤ 4 cm using the Cochet-Bonnet
aesthesiometer) within the area of the PED or corneal ulcer and outside of the area of
the defect in at least one corneal quadrant.

- Best corrected distance visual acuity (BCDVA) score ≤ 75 ETDRS (Early Treatment
Diabetic Retinopathy Study)letters, (≥ 0.2 LogMAR, ≤ 20/32 Snellen or ≤ 0.625 decimal
fraction) in the affected eye(s).

- No objective clinical evidence of improvement in the PED or corneal ulceration within
the 2 weeks prior to study enrolment.

- Only patients who satisfy all Informed Consent requirements may be included in the
study. The patient and/or his/her legal representative must read, sign and date the
Informed Consent document before any study-related procedures are performed. The
Informed Consent form signed by patients and/or legal representative must have been
approved by the IRB (Institutional Review Board) for the current study.

- Patients must have the ability and willingness to comply with study procedures.

Exclusion Criteria:

- Any active ocular infection or active ocular inflammation not related to NK in the
affected eye(s).

- Any other ocular disease requiring topical ocular treatment during the course of the
study treatment period. No topical treatments other than the study medications
provided by the study sponsor and allowed by the study protocol can be administered in
the affected eye(s) during the course of the study treatment periods.

- Patients with severe vision loss with no potential for visual improvement in the
opinion of the investigator as a result of the study treatment.

- Schirmer test without anesthesia ≤3 mm/5 minutes.

- Patients with severe blepharitis and/or severe meibomian gland disease.

- History of any ocular surgery (including laser or refractive surgical procedures)
within the three months before study enrolment. (An exception to the preceding
statement will be allowed if the ocular surgery is considered to be the cause of the
stage 2 or 3 NK). Ocular surgery will not be allowed during the study treatment period
and elective ocular surgery procedures should not be planned during the duration of
the follow-up period.

- Prior surgical procedure(s) for the treatment of NK with the exception of amniotic
membrane transplantation. Patients previously treated with amniotic membrane
transplantation may only be enrolled two weeks after the membrane has disappeared
within the area of the PED or corneal ulcer or at least six weeks after the date of
the amniotic membrane transplantation procedure.

- Patients previously treated with Botox injections used to induce pharmacologic
blepharoptosis are eligible for enrolment only if the last injection was given at
least 90 days prior to enrolment in the study.

- Anticipated need to use therapeutic contact lenses or contact lens wear for refractive
correction during the study treatment period in the eye(s) with NK.

- Anticipated need for punctual occlusion during the study treatment period. Patients
with punctual occlusion or punctual plugs inserted prior to the study are eligible for
enrolment provided that the punctual occlusion is maintained during the study.

- Evidence of corneal ulceration involving the posterior third of the corneal stroma,
corneal melting or perforation.

- Presence or history of any ocular or systemic disorder or condition that might hinder
the efficacy of the study treatment or its evaluation, could possibly interfere with
the interpretation of study results, or could be judged by the investigator to be
incompatible with the study visit schedule or conduct.

- Any need for or anticipated change in the dose of systemic medications known to impair
the function of the trigeminal nerve. These treatments are allowed during the study if
initiated prior study enrolment provided they remain stable throughout the course of
the study treatment periods.

- Known hypersensitivity to one of the components of the study or procedural medications
(e.g. fluorescein).

- History of drug, medication or alcohol abuse or addiction.

- Use of any investigational agent within 4 weeks of screening visit.

- Participation in another clinical study at the same time as the present study.

- Females of childbearing potential are excluded from participation in the study if they
meet any one of the following conditions: are currently pregnant or, have a positive
result on the urine pregnancy test at the Randomization Visit or, intend to become
pregnant during the study treatment period or, are breast-feeding or are not willing
to use highly effective birth control measures.