None listed
Conditions
Brief summary
Chemical injury to the ocular surface has long been recognised to extend over the first 24~48 hours from the initial exposure. This is in part due to transmission of inflammatory signals to the neighbouring cells via the cell-cell connections, called the gap junctions, resulting in inflammatory recruitment and subsequent cell death of the surrounding healthy tissues. Connexin is the building block of these cell junctions; by down-regulating this protein production, we can expect to limit the spread of injury from the initial chemical assault and thereby improve epithelial proliferation and accelerate wound closure. The study aims to assess the efficacy of Nexagon (registered trademark) in the treatment of chemical injuries to the ocular surface. A total of 66 participants will be enrolled. This will include an initial safety study where 6 participants will be enrolled in an open treatment trial, where all participants will receive active treatment to ensure that the Nexagon (registered trademark) dose proposed for the subsequent double-masked phase is safe and well tolerated for human ocular surface injury. Once the safety status is established, recruitment of 60 participants for the double-masked phase of the study will begin. Enrolment of participants will be stratified by severity so that 30 participants of mild severity and 30 participants of moderate / severe severity will be enrolled in total. Within each severity arm, participants will be randomised in 1:1 ratio. Scheduled regular clinical visits will take place to assess progression of the recovery and to monitor safety over the course of the study.
Interventions
Nexagon (registered trademark) - a topical preparation of DNA (Deoxyribonucleic Acid) oligonucleotide molecule that blocks specifically the translation of connexin 43, of which is the building block of one type of gap junctions (cell to cell communication channel).
We will be conducting the trial with a topical agent in a gel formulation. Upon entry in to the main part of the study, all patients will be assessed for severity of their ocular injury to determine the standard of care treatment reg
Nexagon (registered trademark) - a topical preparation of DNA (Deoxyribonucleic Acid) oligonucleotide molecule that blocks specifically the translation of connexin 43, of which is the building block of one type of gap junctions (cell to cell communication channel). We will be conducting the trial with a topical agent in a gel formulation. Upon entry in to the main part of the study, all patients will be assessed for severity of their ocular injury to determine the standard of care treatment regimen that will be initiated prior to the first addition of the study treatment – either Nexagon(registered trademark) or Nexagon (registered trademark) vehicle as placebo. This will be double-masked to both the patient and the treating clinicians. Treatments: Study treatment is given in two parts over Day 1 and Day 2. Part one involves application of study treatment in a 14mm carrier soft (silicon hydrogel) contact lens with a standard dose of 10micrograms/50microlitres of Nexagon (registered trademark) or Nexagon (registered trademark) vehicle. This will stay in for the duration one hour, and then removed. Study treatment is applied again as 6micrograms/100microlitres Nexagon (registered trademark) or Nexagon (registered trademark) vehicle in divided doses over the upper and lower fornices of the affected eye. If the participants fall in the moderate/severe group, they will have again received the standard treatment prior to the second application of Nexagon (registered trademark) or Nexagon (registered trademark) vehicle. Application of the study treatment occurs again on day 2, where the same steps are repeated. If clinically indicated, the severely injured eyes may require amniotic membrane transplant. These patients will then receive a third dose (10micrograms/50microlitres) of study treatment under the transplanted amnion. Other wise, no further application of the trial treatment will be given.
Sponsors
University of Auckland
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Ocular chemical injury with limbal involvement. 2. Subjects with ocular chemical burns within the last 12 hours.
Exclusion criteria
1. Subjects with very mild ocular chemical burns – i.e., those classified as Grade I on the classification system by Dua et al. 2. Subjects presenting with ocular chemical burns ted more than 12 hours after the incident. 3. Subjects who have previously had corneal surgery. 4. Subjects with bilateral ocular surface involvement will have the less injured eye excluded from the study. 5. Subjects with any pre-existing ocular disease or corneal abnormality (complete list in study protocol). 6. Subjects who require any systemic medication that affects healing, e.g., steroids, hormone replacement therapy. 7. Subjects who are taking amiodarone, long acting anticholinergics, e.g., atropine, scopolamine, or medications or agents that can cause dry eye. 8. Subjects who have participated in a clinical trial within the 30 days prior to the date of the chemical injury.
Outcome results
None listed