A 8 Weeks Study to Evaluate Efficacy & Safety of rhNGF vs Vehicle in Patients After Cataract and Refractive Surgery

The primary objective of this exploratory study is to assess preliminary efficacy and safety of rhNGF when administered as eye drops to patients after cataract and refractive surgery.

The main criteria for evaluation were:

* Change from baseline in SANDE scores for severity and frequency assessed at 8 weeks of treatment (primary efficacy endpoint)
* Changes in Cornea vital staining with fluorescein (National Eye Institute \[NEI\] scales) assessed at 8 weeks of treatment (co-primary efficacy endpoint)
* Changes in conjunctiva vital staining with fluorescein (NEI scales) (secondary efficacy endpoint);
* Changes in Tear Film Break-Up Time (TFBUT)(secondary efficacy endpoint);
* Changes in Cochet-Bonnet corneal aesthesiometry (secondary efficacy endpoint);
* Changes in Nerve count and morphology at scanning laser in vivo corneal confocal microscopy (only patients who had Laser-Assisted In situ Keratomileusis \[LASIK\] surgery) (secondary efficacy endpoint);
* Changes in SANDE scores (face values) for severity and frequency (secondary efficacy endpoint);
* Incidence and frequency of treatment-emergent adverse events (TEAEs), assessed throughout the study (safety endpoint).

The proposed phase II study is a single-centre, randomized, double masked, parallel arm, vehicle-controlled trial, designed to evaluate the preliminary efficacy and safety of rhNGF eye drops at 20 µg/ml concentration administered six times daily for 8 weeks in patients who underwent cataract and corneal refractive surgery, both known to damage the corneal sensory nerve plexus.

After confirmation of inclusion and exclusion criteria all eligible patients will be randomized at 2:1 ratio to rhNGF or vehicle control treatment with 8 weeks of study treatments administration with 4 weeks Follow-up.

Eligibility Criteria:
Inclusion Criteria:

1. Male or female ≥18 years old
2. Patients who are characterized by the following clinical features:

   1. History of cataract or refractive corneal surgery in the study eye(s) in the previous 6 months;
   2. Mean Symptom Assessment in Dry Eye (SANDE) score for severity and frequency of at least 30 at baseline
3. The same eye (study eye) must fulfill all the above criteria
4. Best corrected distance visual acuity (BCDVA) score of ≥ 0.1 decimal units in both eyes at the time of study enrolment
5. Female patients must have negative pregnancy urine test if at childbirth potential.
6. Only patients who satisfy all requirements for informed consent may be included in the study. Written Informed Consent must be obtained before the initiation of any study-specific procedures.
7. Patients must have the ability and willingness to comply with study procedures

Exclusion Criteria:

1. Any ocular disease other than Dry Eye requiring treatment with topical medications in either eye at the time of study enrolment.
2. Any active ocular infection or active inflammation in either eye unrelated to Dry Eye.
3. Presence or history of any systemic or ocular disorder, condition or disease (with particular attention to malignancies and neuro-oncological diseases) that could possibly interfere with the conduct of the required study procedures or the interpretation of the study results.
4. Use of therapeutic or Refractive Contact lenses in either eye at the time of study enrolment;
5. History of ocular surgery in the study eye(s), excluding corneal refractive or cataract procedures, within 90 days of study enrolment.
6. Females of childbearing potential (those who are not surgically sterilized or post-menopausal for at least 1 year) are excluded from participation in the study if they meet any one of the following conditions:

   1. are currently pregnant or,
   2. have a positive result at the urine pregnancy test (Baseline/Day 0) or,
   3. intend to become pregnant during the study treatment period or,
   4. are breast-feeding or,
   5. are not willing to use highly effective birth control measures, such as: hormonal contraceptives - oral, implanted, transdermal, or injected - and/or mechanical barrier methods - spermicide in conjunction with a barrier such as a condom or diaphragm or IUD (Intrauterine device) - during the entire course of and 30 days after the study treatment periods.
7. Participation in another clinical study at the same time as the present and within 30 days of study enrolment;
8. History of drug, medication or alcohol abuse or addiction.