A Study to Evaluate Safety and Efficacy of rhNGF Eye Solution vs Vehicle in Patients With Moderate to Severe Dry Eye
Condition: Dry Eye Syndrome
MeSH terms: Dry Eye Syndromes; Keratoconjunctivitis Sicca
Intervention: rhNGF 20 μg/ml; rhNGF 20 μg/ml + vehicle; Vehicle
Intervention description: one drop of rhNGF 20 μg/ml will be instilled in both eyes three times daily (every 6-8 hours); one drop of rhNGF 20 μg/ml will be instilled in both eyes two times daily plus one drop (40 μL) of vehicle will be instilled in both eyes once daily (every 6-8 hours).
rhNGF will be instilled in the morning and in the evening while the vehicle will be instilled in the afternoon.; one drop of vehicle will be instilled in both eyes three times daily (every 6-8 hours)
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Parallel groups
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: Double masked
Enrollment: 261.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No

Summary:

      The objective of this study is to assess the efficacy and safety of rhNGF eye drops at 20
      μg/ml concentration administered two or three times daily for 4 weeks in patients with
      moderate to severe dry eye.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female aged ≥ 18 years

          2. Patients with moderate to severe dry eye characterized by the following clinical
             features:

               1. Corneal and/or conjunctival staining with fluorescein using National Eye
                  Institute (NEI) grading system > 3

               2. SANDE questionnaire >25 mm

               3. Schirmer test I (without anaesthesia) >2mm <10 mm/5 minutes

               4. Tear film break-up time (TFBUT) < 10 seconds in the worse eye

          3. The same eye (eligible eye) must fulfill all the above criteria

          4. Patients diagnosed with dry eye at least 6 months before enrolment (current use or
             recommended use of artificial tears for the treatment of Dry Eye)

          5. Best corrected distance visual acuity (BCDVA) score of ≥ 0.1 decimal units (20/200
             Snellen value) in both eyes at the time of study enrolment

          6. If a female of childbearing potential, have a negative pregnancy test

          7. 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 Institutional Review Board (IRB) / Independent Ethics Committee (IEC)
             for the current study

          8. Patients must have the ability and willingness to comply with study procedures.

        Exclusion Criteria:

          1. Inability to speak and understand the local language sufficiently to understand the
             nature of the study, to provide written informed consent, and to allow the completion
             of all study assessments;

          2. Evidence of an active ocular infection, in either eye

          3. Presence of any other ocular disorder or condition requiring topical medication during
             the entire duration of study

          4. History of severe systemic allergy or of ocular allergy (including seasonal
             conjunctivitis) or chronic conjunctivitis and/or keratitis other than dry eye

          5. Intraocular inflammation defined as Tyndall score >0

          6. History of malignancy in the last 5 years

          7. Systemic disease not stabilized within 1 month before Screening Visit (e.g. diabetes
             with glycemia out of range, 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

          8. Patient 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 anaesthetics or other materials including commercial artificial tears (in
             the opinion of the investigator)

          9. 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 Intra Uterine Device (IUD) - during the entire course of and 30 days
                  after the study treatment periods

         10. Any concurrent medical condition, that in the judgment of the PI, might interfere with
             the conduct of the study, confound the interpretation of the study results, or
             endanger the patient's well-being

         11. Use of topical cyclosporine, topical corticosteroids or any other topical drug for the
             treatment of dry eye in either eye within 30 days of study enrolment.

         12. Contact lenses or punctum plug use during the study (previous use not an exclusion
             criteria but must be discontinued at the screening visit)

         13. History of drug addiction or alcohol abuse

         14. Any prior ocular surgery (including refractive palpebral and cataract surgery) if
             within 90 days before the screening visit

         15. Participation in a clinical trial with a new active substance during the past 6 months

         16. Participation in another clinical trial study at the same time as the present study.