Cacicol20® in Corneal Wound Healing and Nerve Regeneration After Phototherapeutic Keratectomy

Study Overview
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Brief Summary
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The objective of this clinical study is to test the efficacy of CACICOL20® (RGTA OTR 4120) in improving wound healing and nerve regeneration in the anterior cornea, in a patient population undergoing therapeutic laser treatment for corneal dystrophy or recurrent corneal erosions.

Detailed Description
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Patients undergoing various surgical treatments of the cornea often suffer from a neural deficit, due to nerves being severed or removed completely during surgery. This can result in pain, impaired epithelial wound healing, reduced tear production, symptoms of dry eye, and loss of ocular surface sensitivity/blink reflex. In addition, surgical wound healing can be accompanied by undesirable formation of scar tissue, which can limit postoperative visual acuity. The investigators' prior clinical experience with patients having undergone surgery of the anterior cornea is that neural recovery is slow and incomplete, while in certain situations scar tissue can form and limit the visual recovery. In this context, CACICOL20®, a regenerative agent approved for use in healing corneal wounds, presents an interesting opportunity for improving postoperative corneal nerve regeneration and a potentially more rapid restoration of the extracellular matrix environment postoperatively, which can lead to improved neural and visual outcomes. The investigators will therefore evaluate the efficacy of CACICOL20® in a randomized, double-blinded clinical study, to evaluate its ability to promote corneal nerve regeneration, epithelial wound healing, and ocular surface recovery postoperatively. Upon inclusion and signing of informed consent, patients undergo preoperative examination. Upon satisfying study criteria, patients are randomized to either treatment or placebo group. Group identity is masked to subjects and to investigators (double-blind). Subjects then undergo therapeutic laser treatment of the cornea in a single clinic, followed by instillation of treatment or placebo in the form of 3 eye drops total (to be given once immediately after surgery, once 2 days after surgery, and a final time 4 days after surgery). Postoperative eye examinations are conducted on days 2 and 7 and at month 6 and 12. Examinations include clinical measurement of various eye and corneal wound healing parameters.

Official Title
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Cacicol20® in Corneal Wound Healing and Nerve Regeneration After Phototherapeutic Keratectomy of the Anterior Cornea: A Randomized Double-Blinded Placebo-Controlled Study

Conditions
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Corneal Dystrophy, Epithelial Basement Membrane, Epithelial Recurrent Erosion Dystrophy, Corneal Erosions

Intervention / Treatment
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* Device: Cacicol20
* Device: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed and dated informed consent, Male or female aged ≥ 18 years, Patient with recurrent erosions or epithelial dystrophies indicated for treatment by phototherapeutic keratectomy of the anterior cornea Exclusion Criteria: In the affected eye: prior corneal surgery In either eye: active ocular infection, glaucoma, or ocular hypertension General history judged by the investigator to be incompatible with the study (life-threatening patient condition). Known allergic hypersensitivity history to Poly(carboxyMethylGlucoseSulfate) or dextran. Inability of patient to understand the study procedures and thus inability to give informed consent. Participation in another clinical study within the last 3 months. Already included once in this study (can only be included for one treated eye) Specific exclusion criteria for women Known pregnancy (if uncertain pregnancy test will be performed) Lactation Women of childbearing potential without an effective method of contraception (oral contraceptive, intra-uterine device, subcutaneous contraceptive implant, vaginal ring) or women not hysterectomised, post-menopausal or surgically sterilized

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cacicol20<br>Instillation of Cacicol20 eye drops after laser corneal surgery. 3 eye drops total, to be given once immediately after surgery, once 2 days after surgery, and a final time 4 days after surgery. | Device: Cacicol20<br>* Investigational device, regenerating agent, single-use doses, topical eye drops. Indicated for corneal wound healing.<br>* Other names: RGTA OTR 4120;|
| Placebo Comparator: Placebo<br>Instillation of placebo eye drops (vehicle missing the active ingredient) after laser corneal surgery. 3 eye drops total, to be given once immediately after surgery, once 2 days after surgery, and a final time 4 days after surgery. | Device: Placebo<br>* Vehicle only in identical packaging, with identical dosage and administration route.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage recovery in subbasal nerve density. | Degree of corneal subbasal nerve regeneration at one year postoperative, compared to preoperative level, as measured by clinical laser-scanning in vivo confocal microscopy. | 12 months postoperative | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage recovery in subbasal nerve density. | Degree of corneal subbasal nerve regeneration at 6 months postoperative, compared to preoperative level, as measured by clinical laser-scanning in vivo confocal microscopy. | 6 months postoperative | 
| Percentage of epithelial wound closure. | A drop of sodium fluorescein liquid is applied to the cornea, and a digital photograph is taken at high magnification with a clinical slit lamp biomicroscope, using a blue illumination lamp. Area of open wound is measured from photographs and expressed as a percentage of the total treated area. | 2 and 7 days postoperative. | 
| Postoperative pain score on the Visual Analog Scale. | Patient self-assessment using the subjective VAS scale (100 point scale). | Postoperative day 2, 7, month 6, 12 | 
| Corneal haze level. | Corneal haze measured microscopically by clinical in vivo confocal microscopy using a semi-quantitative grading scale. | Postoperative month 6, 12 | 
| Number of postoperative recurrences of erosions. | As reported by the patient. | Postoperative month 12. | 
| Ocular surface sensitivity measured by Cochet-Bonnet esthesiometry. | Central corneal mechanical touch sensitivity in mm measured by Cochet-Bonnet esthesiometry. | Postoperative month 6, 12 | 
| Tear production level | Tear production level (in mm) measured by the Schirmer test without anesthetic. | Postoperative day 7, month 6, 12 | 
| Tear quality | Tear break up time (in seconds) timed by slit lamp biomicroscopic observation after instillation of sodium fluorescein and induction of blinking. | Postoperative day 7, month 6, 12 | 
| Improvement in visual acuity | Distance corrected visual acuity improvement measured in Snellen lines gained/lost relative to preoperative level. | Postoperative day 7, month 6, 12 | 
| Sub basal nerve density measured by clinical in vivo confocal microscopy | Sub basal nerve density level measured by clinical in vivo confocal microscopy. | Postoperative 6 and 12 months | 
| Epithelial cell density measured by clinical in vivo confocal microscopy | Epithelial wing cell density measured by clinical in vivo confocal microscopy. | Postoperative 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Wound healing, nerve regeneration, re-epithelialization, corneal epithelium, laser corneal surgery