Overview

This trial is active, not recruiting.

Conditions neurotrophic keratitis, keratitis, corneal ulcer
Treatments rhngf 10 µg/ml eye drops solution, rhngf 20 µg/ml eye drops solution, placebo
Phase phase 1/phase 2
Sponsor Dompé Farmaceutici S.p.A
Start date January 2013
End date April 2015
Trial size 174 participants
Trial identifier NCT01756456, 2012-002527-15, NGF0212

Summary

This study is aimed at assessing the safety and the efficacy of two dose regimens of recombinant human nerve growth factor (rhNGF) eye drops solution compared to vehicle for inducing a complete healing of stage 2 (persistent epithelial defect) and 3 (corneal ulcer) neurotrophic keratitis

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
rhNGF 10 µg/ml eye drops solution, one drop 6 times a day for 8 weeks in the affected eye only
rhngf 10 µg/ml eye drops solution recombinant human nerve growth factor 10 µg/ml solution
rhNGF 10 µg/ml eye drops solution, one drop 6 times a day for 8 weeks in the affected eye only
(Experimental)
rhNGF 20 µg/ml eye drops solution, one drop 6 times a day for 8 weeks in the affected eye only
rhngf 20 µg/ml eye drops solution recombinant human nerve growth factor 20 µg/ml solution
rhNGF 20 µg/ml eye drops solution, one drop 6 times a day for 8 weeks in the affected eye only
(Placebo Comparator)
Placebo eye drops solution, one drop 6 times a day for 8 weeks in the affected eye only
placebo Vehicle
Placebo eye drops solution, one drop 6 times a day for 8 weeks in the affected eye only.

Primary Outcomes

Measure
Complete healing of the persistent epithelial defect or corneal ulcer
time frame: at 4 weeks of treatment

Secondary Outcomes

Measure
Percentage of patients experiencing complete healing of the persistent epithelial defect or corneal
time frame: at 4 weeks of study treatment.
Percentage of patients experiencing complete healing of the persistent epithelial defect or corneal
time frame: at 6 and 8 weeks after start of the treatment
Percentage of patients experiencing complete corneal clearing epithelial defect
time frame: at 4, 6 and 8 weeks after start of the treatment
Mean change in BCDVA
time frame: At screening and at week 8
Percentage of patients that achieve an improvement in corneal sensitivity
time frame: at 4, 6 and 8 weeks.
Percentage of patients experiencing deterioration in stage 2 or 3 NK
time frame: from baseline to Week 8.

Eligibility Criteria

Male or female participants at least 18 years old.

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). 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. 10. 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. 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 the study or procedural medications (e.g. fluorescein). 15. History of drug, medication or alcohol abuse or addiction. 16. Use of any investigational agent within 4 weeks of screening visit. 17. Participation in another clinical study at the same time as the present study. 18. 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: 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 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 during the entire course of and 30 days after the study treatment periods.

Additional Information

Official 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
Description The primary objective of this study is to assess the safety and the efficacy of two dose regimens (10 µg/ml or 20 µg/ml 6 times a day) of recombinant human nerve growth factor (rhNGF) eye drops solution compared to vehicle for inducing a complete healing of stage 2 (persistent epithelial defect) and 3 (corneal ulcer) neurotrophic keratitis (NK) as measured by the Reading Center evaluating the clinical pictures of corneal fluorescein staining. Secondary objectives of the study are to assess the duration of complete healing, improvement in visual acuity and improvement in corneal sensitivity following treatment with rhNGF eye drops solution This is a combined phase I/II study. The phase I and II segments of the study will be conducted as an 8 week, randomized, double-masked, vehicle controlled, parallel group study (referred to as the controlled treatment period) followed by a 48 or 56 week follow-up period The design of the phase I and phase II segments of the study are identical with the exception that in the phase I segment of the study the randomization scheme is different and patients will be followed with additional safety assessments and blood samples for PK (pharmacokinetic) profiling In the ascending dose Phase I segment of the study two doses of rhNGF 10 and 20 µg/ml will be evaluated in a sequential manner
Trial information was received from ClinicalTrials.gov and was last updated in January 2016.
Information provided to ClinicalTrials.gov by Dompé Farmaceutici S.p.A.