Study Brand Name : REPAROStudy full title: An 8-week phase I/II, multicenter, randomized, double-masked, vehicle controlled parallel group study with a 48 or 56 week follow-up period to evaluate the safety and efficacy of two doses (10 µg/ml and 20 µg/ml) of recombinant human nerve growth factor eye drops solution versus vehicle in patients with Stage 2 and 3 of neurotrophic keratitis

Phase 1

• Conditions: Adult patients diagnosed with unilateral stage 2 (persistent epithelial defect) and stage 3 (corneal ulcer) NK refractory to one or more conventional non-surgical treatments. Patients with Controlateral eye affected with stage 1 NK can be enrolled.; MedDRA version: 18.0Level: LLTClassification code 10032064Term: Other forms of keratitisSystem Organ Class: 100000004853; Therapeutic area: Diseases [C] - Eye Diseases [C11]

• Registration Number: EUCTR2012-002527-15-DE
• Lead Sponsor: Dompé farmaceutici s.p.a

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-12-13
• Last Update Posted: 20 June 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 174

Inclusion Criteria

1. Patients 18 years of age or older.
2. Patients with stage 2 (persistent epithelial defect, PED) or stage 3 (corneal ulcer) neurotrophic keratitis involving only one eye. Patients with Controlateral eye affected with stage 1 NK can be enrolled.
3. PED or corneal ulceration of at least 2 weeks duration refractory to one or more conventional non-surgical treatments for neurotrophic keratitis (e.g., preservative-free artificial tears, gels or ointments; discontinuation of preserved topical drops and medications that can decrease corneal sensitivity; therapeutic contact lenses).
4. 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.
5. Best corrected distance visual acuity (BCDVA) score = 75 ETDRS letters, (= +0.2 LogMAR, = 20/32 Snellen or = 0.625 decimal fraction) in the affected eye.
6. No objective clinical evidence of improvement in the PED or corneal
ulceration within the 2 weeks prior to study enrolment.
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 IEC/IRB for the current study.
8. Patients must have the ability and willingness to comply with study
procedures.
9. Patients must be eligible for the National Health Insurance (where
applicable).

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 74

Exclusion Criteria

1. Patients with stage 2 or 3 NK affecting both eyes.
2. Any active ocular infection (bacterial, viral, fungal or protozoal) or active
ocular inflammation not related to NK in the affected eye.
3. Any other ocular disease requiring topical ocular treatment in the affected eye during the course of the study treatment period. No topical treatments other than the study medications provided by the study sponsor or allowed by the study protocol can be administered in the affected eye during the course of the study treatment periods.
4. Patients with severe vision loss in the affected eye with no potential for visual improvement in the opinion of the investigator as a result of the study treatment.
5. Schirmer test without anesthesia =3 mm/5 minutes in the affected eye.
6. Patients with severe blepharitis and/or severe meibomian gland disease in the affected eye.
7. History of any ocular surgery (including laser or refractive surgical
procedures) in the affected eye 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 in the affected eye 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.
8. Prior surgical procedure(s) for the treatment of NK (e.g. complete tarsorraphy, conjunctival flap, etc) in the affected eye 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 (botulinum toxin) 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.
9. Use of therapeutic contact lenses or contact lens wear for refractive
correction during the study treatment periods in the eye with NK.
Anticipated need for punctual occlusion during the study treatment period.
10. 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.
11. Evidence of corneal ulceration involving the posterior third of the corneal stroma, corneal melting or perforation in the affected eye.
12. 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 (e.g. progressive or degenerative corneal or retinal conditions, uveitis, optic neuritis, poorly controlled diabetes, autoimmune disease, systemic infection, neoplastic diseases).
13. Any need for or anticipated change in the dose of systemic medications known to impair the function of the trigeminal nerve (e.g. neuroleptics, antipsychotic and antihistamine drugs). These treatments are allowed during the study if initiated prior to 30 days before study enrolment provided they remain stable throughout the course of the study treatment periods.
14. Known hypersensitivity to one of the components of th

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified