Trial record 5 of 5 for:    "Herpetic keratitis"

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. No data was collected or analyzed. PI has since left institution)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT01165450
First received: July 15, 2010
Last updated: April 9, 2014
Last verified: April 2014
  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, HSV Keratitis, HZV Keratitis, Corneal Burns, 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 fluoresceing 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. Treament 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.

  • Rate of re-epithelialization of the study eye [ Time Frame: 28 ± 2 days ] [ Designated as safety issue: No ]
    To compare, in each of the two patient populations, the rate of re-epithelialization of the study eye as measured by slit lamp photography with fluorscein.

  • Change in visual acuity from baseline to Day 28 ± 2 in the study eye [ Time Frame: 28 ± 2 days ] [ Designated as safety issue: Yes ]
    Visual acuity will be assessed at every study visit from Day -7 through Day 28 ± 2 using the Snellen visual acuity chart. For the purposes of this study, visual acuity will only be required to be assessed in the study eye.

  • Absolute visual acuity at Day 28 ± 2 in the study eye [ Time Frame: 28 ± 2 days ] [ Designated as safety issue: Yes ]
    To determine absolute visual acuity at Day 28 ± 2, using baseline as a covariate. Visual acuity will be assessed in the study eye using the Snellen visual acuity chart.

  • Ocular abnormalities in the study eye from baseline to Day 28 ± 2 [ Time Frame: 28 ± 2 days ] [ Designated as safety issue: Yes ]
    Ocular abnormalities detected by slit lamp biomicroscopy will be scored with a grading scale from baseline to Day 28 ± 2 in the study eye. Ocular abnormalities will be assessed in the lid, conjunctiva, cornea, and anterior chamber. Abnormalities will include erythema, edema, staining/erosion, abnormal cells, and flare.

  • Subjective evaluation of ocular symptoms from baseline to Day 14± 1 or Day 28 ± 2 in study eye [ Time Frame: 28 ± 2 days ] [ Designated as safety issue: Yes ]
    To determine the subjective evaluation of ocular symptoms from baseline to Day 14 ± 1 or Day 28 ± 2 in the study eye. Severity and frequency of each symptom will be determined by questioning the subject with regard to pain, photophobia, foreign body sensation, burning, stinging, tearing, and itching.

  • Tear film production of the study eye [ Time Frame: 28 ± 2 days ] [ Designated as safety issue: Yes ]
    Tear film production in the study eye will be measured by a Schirmer Test at Day 0 ± 1 and on Day 28 ± 2, or when complete re-epithelialtization is achieved in the study eye. Results will be record in millimeters (mm) of wetting.

  • Neurotrophic corneal sensation at Day 28 ± 2 in the study eye [ Time Frame: 28 ± 2 days ] [ Designated as safety issue: No ]
    Neurotrophic corneal sensation will be measured by the dental floss test in four quadrants (plus center) of the study eye at Day 28 ± 2. Sensation will be quantified as full sensation, decreased sensation, or no sensation.

  • Validity and reliability of ImageJ software in measuring the size of epithelial defects [ Time Frame: 28 ± days ] [ Designated as safety issue: No ]
    The validity and reliability of ImageJ software in measuring the size of epithelial defects will be assessed by comparing Image J analyses of digital photos to measurements performed by Investigator, or designated ophthalmologist, using slit lamp examination with fluorescein staining. Photographs will be read by 3 masked reviewers (trained technicians), and the average of the areas from the 3 reviewers will be used as the measurement for comparison.

  • Sub-population and subject characteristic analysis of outcomes [ Time Frame: 28 ± 2 days ] [ Designated as safety issue: No ]
    The effect of the study medication on the above outcomes will be further assessed by looking at other subpopulations and other characteristics of the subjects recruited, including the type of vitrectomy surgery that was performed, the length of time of surgery, the gauge of vitrectomer (20 vs. 24 gauge), prior persistent epithelial defect, a history of persistent epithelial defects, and Hb1Ac as an indicator of the severity of diabetes. The duration of HSV and HZV keratitis will also be investigated as a variable.

  • Probability of healing at 14 ± 1 days [ Time Frame: 14 ± 1 days ] [ Designated as safety issue: No ]
    To compare the probability of healing 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.

  • Probability of healing at 28 ± 2 days [ Time Frame: 28 ± 2 days ] [ Designated as safety issue: No ]
    To compare the probability of healing at 28 ± 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.


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
Last Updated: April 9, 2014
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 September 30, 2014