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

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ClinicalTrials.gov Identifier: NCT01165450
Recruitment Status : Terminated (Drug manufacturer could not supply study drug.)
First Posted : July 19, 2010
Results First Posted : April 20, 2015
Last Update Posted : May 7, 2015
Sponsor:
Collaborator:
FDA Office of Orphan Products Development
Information provided by (Responsible Party):
University of California, San Francisco

Tracking Information
First Submitted Date  ICMJE July 15, 2010
First Posted Date  ICMJE July 19, 2010
Results First Submitted Date  ICMJE April 7, 2015
Results First Posted Date  ICMJE April 20, 2015
Last Update Posted Date May 7, 2015
Study Start Date  ICMJE November 2011
Actual Primary Completion Date February 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 20, 2011)
  • Percent Healing of the Corneal Epithelial Defect at Day 14 ± 1 in the Study Eye [ Time Frame: 14 ± 1 days ]
    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 ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: July 16, 2010)
Complete healing of the corneal epithelial defect at Day 14 in the study eye [ Time Frame: 14 days ]
Change History Complete list of historical versions of study NCT01165450 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 7, 2015)
  • Time to Complete Re-epithelialization of the Study Eye [ Time Frame: 28 ± 2 days ]
    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 ]
    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 ]
    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 ]
    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 ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 16, 2010)
Incidence of adverse events following application of the investigational product in all subjects [ Time Frame: 28 days ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety Study of Nexagon for Persistent Corneal Epithelial Defects
Official Title  ICMJE 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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Persistent Corneal Epithelial Defects
Intervention  ICMJE
  • 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
  • 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
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Nexagon
  • 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.
    Intervention: Drug: Vehicle only
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: April 8, 2014)
2
Original Estimated Enrollment  ICMJE
 (submitted: July 16, 2010)
72
Actual Study Completion Date  ICMJE February 2014
Actual Primary Completion Date February 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries United States
 
Administrative Information
NCT Number  ICMJE NCT01165450
Other Study ID Numbers  ICMJE Nex001
1R01FD003708-01A1 ( U.S. FDA Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of California, San Francisco
Study Sponsor  ICMJE University of California, San Francisco
Collaborators  ICMJE FDA Office of Orphan Products Development
Investigators  ICMJE
Principal Investigator: Bennie H Jeng, MD University of California, San Francisco
PRS Account University of California, San Francisco
Verification Date April 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP