Clinical trial NCT01165450: Efficacy and Safety Study of Nexagon for Persistent Corneal Epithelial Defects
Official title: Phase 2, Randomized, Double-masked, Vehicle-controlled, Dose-escalation Study Evaluating Efficacy/Safety of Nexagon in Subjects With Persistent Corneal Epithelial Defects (PED) Resulting From Corneal Epithelial Debridement During Diabetic Vitrectomy Surgery, Herpes Simples Virus (HSV) Keratitis, Herpes Zoster Virus (HZV) Keratitis, Corneal Burns, Post-photorefractive Keratectomy (Post-PRK), or Post-corneal Transplant Surgery.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Persistent Corneal Epithelial Defects
Keywords: persistent epithelial defect
cornea
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: FDA Office of Orphan Products Development
First posted: 2010-07-19
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and safety of Nexagon® in subjects with persistent corneal epithelial defects (PED) resulting from corneal epithelial debridement during diabetic vitrectomy surgery, HSV keratitis, HZV keratitis, corneal burns, post-PRK, or post-corneal transplant surgery.

Detailed description: The purpose of this prospective, randomized, double-masked, vehicle-controlled, dose-escalation study is to evaluate the efficacy and safety of Nexagon® in subjects with persistent corneal epithelial defects (PED) resulting from corneal epithelial debridement during diabetic vitrectomy surgery, HSV keratitis, HZV keratitis, corneal burns, post-PRK, or post-corneal transplant surgery. In general, traditional therapy of PED consists of aggressive lubrication with preservative-free artificial tears and ointments, the use of bandage soft contact lenses, pressure patching, punctal plugging, and the surgical closure of the eyelids. Unfortunately, the success rates with these conventional treatment modalities are varied, and overall, disappointingly low. As such, much research is currently being directed at finding better treatments for PED. Nexagon® is a novel therapeutic agent that has been shown to be effective in treating skin lesions, and it has been shown in animal studies and in preliminary human studies to be safe and efficacious in treating PED.

Eligibility criteria: Inclusion Criteria:

* Male and female subjects aged 18 years and over.
* Female subjects must be a) postmenopausal, b) surgically sterilized, c) practicing abstinence, or d) using a hormonal contraceptive, intrauterine device, diaphragm with spermicide, or condom with spermicide for the duration of the study.
* Subjects who are able to attend all follow-up visits and who are able to comply with all study procedures.
* Subjects who are willing and able to give written informed consent to take part in the study.
* Subjects with a PED, defined as follows: "a corneal epithelial defect persisting for at least 14 days and not longer than 28 days."
* In the Investigator's opinion, the defect is persistent i.e., the defect has not shown improvement despite conventional treatment such as tear supplements and bandage contact lenses.
* The original defect to the cornea must have resulted from corneal epithelial debridement during diabetic vitrectomy surgery, HSV keratitis, HZV keratitis, corneal burns, post-PRK, or post-corneal transplant surgery.

Exclusion Criteria:

* Use of concomitant ocular medications in the screening period that are not specified in standardized PED treatment regimen
* Likely to require the use of concomitant ocular medications that are not specified in the standardized PED treatment regime during the study follow-up period
* Decrease or increase in the PED by more than 50% during the screening period.
* Have an active eyelid or ocular infectious process of any sort, in the opinion of the Investigator.
* Subjects with corneal perforation or impending corneal perforation.
* Subjects with severe eyelid abnormalities contributory to the persistence of the PED.
* Subjects with bilateral PED, if the smaller PED has a longest diameter of \> 2 mm. (Note: if bilateral PED is present and the smaller PED is \< 2 mm, the subject is eligible. In this situation only the eye with the larger PED should be entered into the study).
* Female subjects who are pregnant or breastfeeding. Female subjects who are neither postmenopausal nor surgically sterile require a negative urine pregnancy test on Day 0 (plus or minus 1 day) visit.
* Subjects who have a history of AIDS or HIV.
* Subjects with any other condition which, in the Investigator's opinion, would exclude the subject from participating.
* Treatment with systemic corticosteroids (equivalent to \> 10 mg/day of prednisone) or immunosuppressive or chemotherapeutic agents within 7 days prior to Day 0 (plus or minus 1 day) visit, or likely to receive one of these therapies during study participation
* Subjects who have participated in a clinical trial within 30 days prior to Day 0 (plus or minus 1 day) visit.

Primary outcomes:
measure: Percent Healing of the Corneal Epithelial Defect at Day 14 ± 1 in the Study Eye
timeFrame: 14 ± 1 days
measure: Incidence of Adverse Events Following Application of the Investigational Product in All Subjects
timeFrame: 28 ± 2 days
Secondary outcomes:
measure: Time to Complete Re-epithelialization of the Study Eye
timeFrame: 28 ± 2 days
measure: Complete Healing of the Corneal Epithelial Defect at Day 14 ± 1 in the Study Eye
timeFrame: 14 ± 1 days
measure: Change in the Rate of Re-epithelialization of the Study Eye
timeFrame: 35 ± 2 days
measure: Persistence of Complete Corneal Re-epithelialization in the Study Eye
timeFrame: 28 ± 2 days
measure: Percent Reduction of Corneal Epithelial Defect at Day 28 ± 2 in the Study Eye
timeFrame: 28 ± 2 days
Other outcomes:
Locations:
Study officials:
affiliation: University of California, San Francisco
name: Bennie H Jeng, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Qiu C, Coutinho P, Frank S, Franke S, Law LY, Martin P, Green CR, Becker DL. Targeting connexin43 expression accelerates the rate of wound repair. Curr Biol. 2003 Sep 30;13(19):1697-703. doi: 10.1016/j.cub.2003.09.007.
citation: Lin JH, Weigel H, Cotrina ML, Liu S, Bueno E, Hansen AJ, Hansen TW, Goldman S, Nedergaard M. Gap-junction-mediated propagation and amplification of cell injury. Nat Neurosci. 1998 Oct;1(6):494-500. doi: 10.1038/2210.