Efficacy and Safety Study of Nexagon for Persistent Corneal Epithelial Defects (NTX-PED-001)

This study has been terminated.
(Drug manufacturer could not supply study drug.)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT01165450
First received: July 15, 2010
Last updated: April 20, 2015
Last verified: April 2015
  Purpose

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.


Condition Intervention Phase
Persistent Corneal Epithelial Defects
Drug: Nexagon
Drug: Vehicle only
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Percent Healing of the Corneal Epithelial Defect at Day 14 ± 1 in the Study Eye [ Time Frame: 14 ± 1 days ] [ Designated as safety issue: No ]
    Primary efficacy measure: To determine whether topical treatment of persistent epithelial defects with Nexagon preparations yields greater healing at Day 14 ± 1, compared to vehicle alone, in individuals having had diabetic vitrectomy. Healing will be determined by comparing pseudo-area (as measured by Investigator, or designated ophthalmologist) at baseline (taken just prior to the first treatment) and Day 14 ± 1. Pseudo-area is defined by the longest diameter of the lesion multiplied by the longest perpendicular to this longest diameter.

  • Incidence of Adverse Events Following Application of the Investigational Product in All Subjects [ Time Frame: 28 ± 2 days ] [ Designated as safety issue: Yes ]
    Primary safety measure: To determine incidence of adverse events by recording their occurrence at each study visit through Day 28 ± 2. Analysis of safety data will be performed prior to each dose-escalation. If greater than 2 serious adverse events are found that are causally related to the investigational product, the study will be halted.


Secondary Outcome Measures:
  • Time to Complete Re-epithelialization of the Study Eye [ Time Frame: 28 ± 2 days ] [ Designated as safety issue: No ]
    Resolution of epithelial defect is defined as the largest diameter of the epithelial defect being less than 0.5 mm, as it is difficult to distinguish a smaller defect from the small amount of fluorescing staining seen in a healed defect. Time of complete re-epithelialization will be defined as the midpoint between the last observed date with an epithelial defect and the date of the first visit with no epithelial defect, up to Day 28 ± 2.

  • Complete Healing of the Corneal Epithelial Defect at Day 14 ± 1 in the Study Eye [ Time Frame: 14 ± 1 days ] [ Designated as safety issue: No ]
    To determine binary indicator of whether or not healing has occurred at 14 ± 1 days, defined as the largest diameter of the epithelial defect being smaller than 0.5 mm as determined by slit lamp examination with fluorescein staining.

  • Change in the Rate of Re-epithelialization of the Study Eye [ Time Frame: 35 ± 2 days ] [ Designated as safety issue: No ]

    To determine the change in the rate of re-epithelialization of the study eye from the screening run-in period to the treatment period, if applicable.

    Time Frame: Screening period is defined as Day -7 to Day 0 ± 1. Treatment period is defined as Day 0 ± 1 through time of complete re-epithelialization. Time of complete re-epithelialization is defined as the midpoint between the last observed date with an epithelial defect and the date of the first visit with no epithelial defect, up to Day 28 ± 2.


  • Persistence of Complete Corneal Re-epithelialization in the Study Eye [ Time Frame: 28 ± 2 days ] [ Designated as safety issue: No ]
    To determine whether or not complete corneal re-epithelialization was persistent, as determined by whether the healed epithelium remains intact after complete re-epithelialization is confirmed in the study eye. The measurement will be made at Day 28 ± 2.

  • Percent Reduction of Corneal Epithelial Defect at Day 28 ± 2 in the Study Eye [ Time Frame: 28 ± 2 days ] [ Designated as safety issue: No ]
    To compare, in each of the two patient populations, the percent reduction in epithelial defect size at Day 28 ± 2 compared to baseline, as measured by slit lamp examination with fluorescein staining. Epithelial defect size determined by pseudo-area, defined by the longest diameter of the lesion multiplied by the longest perpendicular to this longest diameter.


Enrollment: 2
Study Start Date: November 2011
Study Completion Date: February 2014
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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.
Drug: 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.
Other Names:
  • Active Ingredient: CODA001
  • IND: 104593
  • Vehicle: Poloxamer 407
Placebo Comparator: 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.
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.
Other Name: Poloxamer 407

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01165450

Sponsors and Collaborators
University of California, San Francisco
Investigators
Principal Investigator: Bennie H Jeng, MD University of California, San Francisco
  More Information

Publications:
Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01165450     History of Changes
Other Study ID Numbers: Nex001, 1 R01 FD003708-01A1
Study First Received: July 15, 2010
Results First Received: April 7, 2015
Last Updated: April 20, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by University of California, San Francisco:
persistent epithelial defect
cornea

ClinicalTrials.gov processed this record on August 26, 2015