An 8-week Study to Evaluate Safety and Efficacy of NGF Eye Drops Solution Versus Vehicle in Patients With Dry Eye

An 8-week, Phase II, Single-center, Randomized, Double-masked, Vehicle-controlled, Parallel-group Study With 4 Weeks of Follow-up to Evaluate Safety and Efficacy of rhNGF Eye Drops Solution vs Vehicle in Patients With Dry Eye

The primary objective of this study was to assess the efficacy and safety of rhNGF when administered as eye drops to patients with dry eye

The secondary objectives of this study were:

• To assess change from baseline in Symptom Assessment In Dry Eye (SANDE) scores (without imputation), corneal and conjunctival staining according to National Eye Institute (NEI) scale, and in Tear Film Break-up Time (TFBUT) and Schirmer test I, following 4 and 8 weeks of treatment.
• To assess change in levels of inflammatory biomarker matrix metallopeptidase 9 (MMP-9) in tears following 8 weeks of treatment.
• To assess the incidence and frequency of treatment-emergent adverse events (TEAEs) following 8 weeks of treatment.

The proposed phase II study is a single-center, randomized, double-masked, parallel-arm, vehicle-controlled trial, designed to evaluate the safety and efficacy of Recombinant Human Nerve Growth Factor (rhNGF) eye drops at 20 μg/ml concentration administered six times daily for 8 weeks in patients with dry eye. 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.

Inclusion Criteria:

1. Patients (male or female) must be ≥ 18 years of age.

2. Patients must be diagnosed with any type of dry eye (e.g. Meibomian Gland Dysfunction, Blepharitis, Keratoconjunctivitis sicca etc) at least 3 months before enrollment.

3. Patients must present dry eye pathology characterized by the following clinical features:

   1. Corneal and/or conjunctival staining with fluorescein and lissamine green using National Eye Institute (NEI) grading system > 3
   2. Mean Symptom Assessment in Dry Eye (SANDE) questionnaire ≥30
   3. Schirmer test without anesthesia < 10 mm/5 minutes and/or tear film break-up time (TFBUT) < 10 seconds in the study eye

4. The same eye (study eye) must fulfill all the above criteria.

5. Patients must have best corrected distance visual acuity (BCDVA) score of ≥ 0.1 decimal units in both eyes at the time of study enrollment.

6. Female patients must have negative pregnancy test if at childbirth potential.

7. 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.

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

Exclusion Criteria:

1. Best corrected distance visual acuity (BCDVA) score of < 0.1 decimal units in either eye.

2. Evidence of an active ocular infection in either eye.

3. Presence or history of any ocular disorder or condition, including ocular surgery, trauma, or disease that could possibly interfere with the interpretation of study results in the opinion of the Investigator.

4. Intraocular inflammation defined as Tyndall score >0.

5. Active or recent diagnosis of malignancy (i.e., currently under chemo/radiotherapy).

6. Systemic disease not stabilized within 1 month before baseline visit (e.g., uncontrolled diabetes; thyroid malfunction) or judged by the Investigator to be incompatible with the study (e.g., current systemic infections) or with a condition incompatible with the frequent assessment required by the study.

7. Patients who have had a serious adverse reaction or significant hypersensitivity to any drug or chemically related compounds, or had a clinically significant allergy to drugs, foods, amide local anesthetics, or other materials, including commercial artificial tears containing carboxymethylcellulose (CMC) (in the opinion of the Investigator).

8. Use of topical cyclosporine, topical corticosteroids, or any other topical medication for the treatment of dry eye in either eye until the day of study enrollment.

9. Contact lenses or punctal plug use during the study (previous use not an exclusion criteria, but must be discontinued at the baseline visit.

10. An anticipated need of additional systemic treatments for dry eye during the study (all prior treatment must be continued for the entire duration of the study).

11. Females of childbearing potential (those who are not surgically sterilized or postmenopausal 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 a intrauterine device (IUD) - during the entire course of and 30 days after the study treatment periods.

12. History of drug addiction or alcohol abuse.

13. Any prior ocular surgery (including refractive palpebral and cataract surgery) if within 90 days before the screening visit.

14. Participation in a clinical trial with a new active substance during the past 30 days.

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