Efficacy and Safety Study of Nexagon for Persistent Corneal Epithelial Defects

NCT ID: NCT01165450

Last Updated: 2015-05-07

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-30
• Study Completion Date: 2014-02-28

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.

Conditions

Persistent Corneal Epithelial Defects

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Nexagon

There will be 3 groups of patients with persistent epithelial defects, treated in a dose-escalation fashion from 1µg to 3µg to 10 µg. Each group will consist of 18 patients randomized to Nexagon and 6 patients randomized to placebo only.

Group Type: ACTIVE_COMPARATOR

Nexagon

Intervention Type: DRUG

There will be 3 groups of patients with persistent epithelial defects, treated in a dose-escalation fashion from 1µg to 3µg to 10 µg. Each group will consist of 18 patients randomized to Nexagon and 6 patients randomized to placebo only.

Vehicle only

There will be 3 groups of patients with persistent epithelial defects, treated in a dose-escalation fashion from 1µg to 3µg to 10 µg. Each group will consist of 18 patients randomized to Nexagon and 6 patients randomized to placebo only.

Group Type: PLACEBO_COMPARATOR

Vehicle only

Intervention Type: DRUG

There will be 3 groups of patients with persistent epithelial defects, treated in a dose-escalation fashion from 1µg to 3µg to 10 µg. Each group will consist of 18 patients randomized to Nexagon and 6 patients randomized to placebo only.

Interventions

Nexagon

There will be 3 groups of patients with persistent epithelial defects, treated in a dose-escalation fashion from 1µg to 3µg to 10 µg. Each group will consist of 18 patients randomized to Nexagon and 6 patients randomized to placebo only.

Intervention Type: DRUG

Vehicle only

There will be 3 groups of patients with persistent epithelial defects, treated in a dose-escalation fashion from 1µg to 3µg to 10 µg. Each group will consist of 18 patients randomized to Nexagon and 6 patients randomized to placebo only.

Intervention Type: DRUG

Other Intervention Names

Active Ingredient: CODA001; IND: 104593; Vehicle: Poloxamer 407; Poloxamer 407

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

FDA Office of Orphan Products Development

FED

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bennie H Jeng, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

References

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.

Reference Type: BACKGROUND

PMID: 14521835 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 10196547 (View on PubMed)

Other Identifiers

1R01FD003708-01A1

Identifier Type: FDA

Identifier Source: secondary_id

View Link

Nex001

Identifier Type: -

Identifier Source: org_study_id