Persistent Corneal Epithelial DefectsPhase 2NTX-PED-001NCT01165450
Efficacy and Safety Study of Nexagon for Persistent Corneal Epithelial Defects
A Phase 2 study testing Nexagon in people with Persistent Corneal Epithelial Defects, run by University of California, San Francisco.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Persistent Corneal Epithelial Defects
- What is being tested?
- Nexagon
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2 participants
- Where
- No sites listed yet
- Study dates
- Nov 2011to Feb 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
About this study
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.
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.
Read the 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
- Being tested
- Nexagon, Vehicle only
- Keywords
- persistent epithelial defect, cornea
- Medical subject headings
- Corneal Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NexagonDrug
Also called Active Ingredient: CODA001, IND: 104593, Vehicle: Poloxamer 407
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 onlyDrug
Also called Poloxamer 407
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Vehicle only |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 28 ± 2 days
Secondary outcomes (5)
Time to Complete Re-epithelialization of the Study Eye
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.
Measured: 28 ± 2 days
Complete Healing of the Corneal Epithelial Defect at Day 14 ± 1 in the Study Eye
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.
Measured: 14 ± 1 days
Change in the Rate of Re-epithelialization of the Study Eye
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.
Measured: 35 ± 2 days
Persistence of Complete Corneal Re-epithelialization in the Study Eye
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.
Measured: 28 ± 2 days
Percent Reduction of Corneal Epithelial Defect at Day 28 ± 2 in the Study Eye
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.
Measured: 28 ± 2 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2010 (estimated)
- Study startNov 2011
- Primary completionFeb 2014
- Study completionFeb 2014
Why it stopped: Drug manufacturer could not supply study drug.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Persistent Corneal Epithelial DefectsStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- FDA Office of Orphan Products Development
- Responsible party
- Sponsor
- Investigators
- Bennie H Jeng, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01165450
- Sponsor's protocol ID
- Nex001
- Other IDs
- 1R01FD003708-01A1
- Acronym
- NTX-PED-001
- Status last verified
- Apr 2015
- First submitted
- 15 Jul 2010
- Last updated
- 7 May 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 14521835Lin 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.
PubMed 10196547
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01165450
- Acronym / sponsor ID
- NTX-PED-001 / Nex001
- Conditions
- Persistent Corneal Epithelial Defects
- Keywords
- persistent epithelial defect, cornea
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Drug manufacturer could not supply study drug.
- Enrolment
- 2 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- FDA Office of Orphan Products Development
- Study start
- Nov 2011
- Primary completion
- Feb 2014 (actual)
- Study completion
- Feb 2014 (actual)
- First posted
- 19 Jul 2010 (estimated)
- Results
- Posted 20 Apr 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nexagon | Active comparator | Drug: NexagonThere 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 | Placebo comparator | Drug: Vehicle onlyThere 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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."
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NexagonAlso: Active Ingredient: CODA001, IND: 104593, Vehicle: Poloxamer 407There 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 onlyAlso: Poloxamer 407There 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 |
Primary outcome
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.
5 secondary outcomes
Time to Complete Re-epithelialization of the Study Eye
Time frame: 28 ± 2 days
Complete Healing of the Corneal Epithelial Defect at Day 14 ± 1 in the Study Eye
Time frame: 14 ± 1 days
Change in the Rate of Re-epithelialization of the Study Eye
Time frame: 35 ± 2 days
Persistence of Complete Corneal Re-epithelialization in the Study Eye
Time frame: 28 ± 2 days
Percent Reduction of Corneal Epithelial Defect at Day 28 ± 2 in the Study Eye
Time frame: 28 ± 2 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 14521835Qiu 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.
- Background: PubMed 10196547Lin 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bennie H Jeng, MD principal investigator
University of California, San Francisco
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nexagon in people with Persistent Corneal Epithelial Defects, run by University of California, San Francisco.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 7 May 2015. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Apr 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Healing of the Corneal Epithelial Defect at Day 14 ± 1 in the Study Eye (time frame: 14 ± 1 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01165450, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 May 2015.