Efficacy and Safety Study of Nexagon for Persistent Corneal Epithelial Defects

NCT01165450 | Terminated Phase 2 Results DMC

• 2 other identifiers: Nex0011R01FD003708-01A1
• Study Type: interventional
• Target: 2
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Persistent Corneal Epithelial Defects

Keywords

persistent epithelial defect; cornea

Outcome Measures

Primary Outcomes (2)

• Percent Healing of the Corneal Epithelial Defect at Day 14 ± 1 in the Study Eye

  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.

  14 ± 1 days

• Incidence of Adverse Events Following Application of the Investigational Product in All Subjects

  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.

  28 ± 2 days

Secondary Outcomes (5)

• Time to Complete Re-epithelialization of the Study Eye

  28 ± 2 days

• Complete Healing of the Corneal Epithelial Defect at Day 14 ± 1 in the Study Eye

  14 ± 1 days

• Change in the Rate of Re-epithelialization of the Study Eye

  35 ± 2 days

• Persistence of Complete Corneal Re-epithelialization in the Study Eye

  28 ± 2 days

• Percent Reduction of Corneal Epithelial Defect at Day 28 ± 2 in the Study Eye

  28 ± 2 days

Study Arms (2)

Nexagon

ACTIVE COMPARATOR

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

Vehicle only

PLACEBO COMPARATOR

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

Interventions

Nexagon 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.

Also known as: Active Ingredient: CODA001, IND: 104593, Vehicle: Poloxamer 407

Nexagon

Vehicle only 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.

Also known as: Poloxamer 407

Vehicle only

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of California, San Francisco: lead
• FDA Office of Orphan Products Development: collaborator

Related Publications (2)

• 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.

  PMID: 14521835 BACKGROUND

• 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.

  PMID: 10196547 BACKGROUND

MeSH Terms

Conditions

Corneal Diseases

Interventions

Poloxamer

Condition Hierarchy (Ancestors)

Eye Diseases

Intervention Hierarchy (Ancestors)

Polyethylene Glycols; Ethylene Glycols; Glycols; Alcohols; Organic Chemicals; Polymers; Macromolecular Substances; Biomedical and Dental Materials; Manufactured Materials; Technology, Industry, and Agriculture

Limitations and Caveats

The study was terminated prematurely due to discontinued supply of study drug, and data were never analyzed; PI has left the institution and data are no longer available.

Results Point of Contact

• Title: Bennie H. Jeng, MD, MS
• Organization: University of Maryland School of Medicine

bjeng@som.umaryland.edu

667-214-1111

Study Officials

• Bennie H Jeng, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2010
• First Posted: July 19, 2010
• Study Start: November 1, 2011
• Primary Completion: February 1, 2014
• Study Completion: February 1, 2014
• Last Updated: May 7, 2015
• Results First Posted: April 20, 2015

Record last verified: 2015-04