Evaluation of Efficacy of 20 µg/ml rhNGF New Formulation (With Anti-oxidant) in Patients With Stage 2 and 3 NK
Condition: Neurotrophic Keratitis
MeSH terms: Keratitis
Intervention: rhNGF 20µg/ml; Placebo
Intervention description: Formulation containing antioxidant
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 48.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Neurotrophic Keratitis

Summary:

      The primary objective of this study is to evaluate the efficacy of 20 µg/ml 6 times a day of
      rhNGF eye drops solution (formulation containing anti-oxidant) compared to vehicle
      (formulation containing anti-oxidant) given 6 times a day. The evaluation of efficacy is
      intended as:

        -  complete healing of stage 2 (persistent epithelial defect) and 3 (corneal ulcer)
           neurotrophic keratitis (NK) as measured by the central reading center using corneal
           fluorescein staining,

        -  assessing the duration of complete healing,

        -  improvement in visual acuity and improvement in corneal sensitivity.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients 18 years of age or older.

          -  Patients with stage 2 (persistent epithelial defect, PED) or stage 3 (corneal ulcer)
             neurotrophic keratitis (NK).

          -  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.