Neuropathic Pain
Conditions
Brief summary
The primary objective of this study, in subjects with Neuropathic Corneal Pain, is to evaluate the efficacy and safety of OK-101 0.05% and 0.1% as compared to placebo instilled 4 times/day in subjects with neuropathic corneal pain, as assessed by visual analogue scale (VAS).
Detailed description
Detailed Description: Neuropathic corneal pain (NCP) is a complex disease affecting the somatosensory nervous system characterized by different underlying etiologies and pathogenesis. OK-101 is a lipid conjugated chemerin peptide antagonist of the ChemR23 G-protein coupled receptor which is typically found on immune cells of the eye responsible for the inflammatory response. OK-101 has been shown to produce anti-inflammatory and pain-reducing activities in mouse models of dry eye disease and neuropathic corneal pain; and is designed to combat washout through the inclusion of the lipid 'anchor' contained in the candidate drug molecule to enhance the residence time of OK-101 within the ocular environment. Our preclinical studies have shown that treatment with OK-101 abolishes corneal pain in a murine model of NCP.
Interventions
DRUGOK-101 0.05%
0.05% Ophthalmic Solution
DRUGOK-101 0.1%
0.1% Ophthalmic Solution
DRUGPlacebo
Placebo
Sponsors
Tufts Medical Center
Okyo Pharma Ltd
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
This is a randomized, double-masked, placebo-controlled trial to investigate the efficacy of OK101 study drug in treating the symptoms of NCP at baseline (Visit 1) through the end of study (16 weeks) in NCP subjects.
Intervention model description
Approximately 48 subjects will be randomized in a 1:1:1 ratio to receive treatment with 0.05% OK-101 (Arm A) or 0.1% OK-101 (Arm B) or placebo (Arm C).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female aged ≥ 18 years. 2. Symptoms of neuropathic corneal pain for at least 3 months, such as burning, stinging, light sensitivity, discomfort, or pain. 3. Positive IVCM findings evaluated by an experienced ophthalmologist (Pedram Hamrah, M.D.): decreased nerve density AND evidence of microneuromas. 4. Females of childbearing potential must have a negative pregnancy test. 5. Best corrected distance visual acuity (BCDVA), using corrective lenses, if necessary, in the study eye of at least +1.0 Log MAR (Snellen \<20/200). 6. Satisfying all Informed Consent requirements. 7. Ability and willingness to comply with study procedures.
Exclusion criteria
1. Evidence of any active ocular infection. 2. Evidence of any intraocular inflammation. 3. Evidence of any persistent epithelial defect/ulcer. 4. Evidence of any corneal scar/corneal edema. 5. Presence of any other ocular conditions that require topical medications during the treatment phase. 6. History of severe systemic allergy or severe ocular allergy. 7. Inability to suspend topical medications 8 days prior to the starting date. 8. Inability to continue oral medications for NCP without changes during the study duration. 9. No changes or less than 50% improvement in VAS score after topical 0.5% proparacaine hydrochloride (Alcaine, Alcon, Fort Worth, TX). 10. History of any ocular surgery within three months before study Visit 1(day 0). 11. Ocular surgery expected during the 16 weeks of the trial. 12. Use of refractive/therapeutic contact lenses during the study period. 13. Female subjects who are pregnant/have a positive pregnancy test result or are breastfeeding or intend to become pregnant during the study treatment period. 14. Drug addiction/alcohol abuse within the last year. 15. Participation in another clinical trial concurrently.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assess ocular pain using 0-10 visual analog scale (VAS) | 16 Weeks | Visual analog scale questionaire will be used to evaluate the pain on 0-10 scale where 0 is no pain and 10 is worst pain imaginable. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ocular Pain Assessment Survey (OPAS) scores | 16 Weeks | Twenty-seven item questionnaires specifically designed to assess symptoms and quality of life in ocular pain. |
| Ocular Surface Disease Index (OSDI©) scores | 16 Weeks | Twelve-item questionnaire to assess symptoms of ocular irritation consistent with dry eye and their impact on vision-related functioning. |
| QoL Improvement assesed by OPAS score | 16 Weeks | Twenty-seven item questionnaires specifically designed to assess symptoms and quality of life in ocular pain |
| Drop comfort Scores | 16 Weeks | Drop Comfort will be assesed using Scale 0-10, with a value of 0 being most comfortable and 10 being least comfortable. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Asses corneal nerve regeneration by measuring change in total length of corneal nerve regeneration | 16 Weeks | Change in total length of all nerves within an image (in mm/mm2) will be evaulated via In-Vivo Confocal Microscopy (IVCM) imaging |
| Assess change in numbers of microneuromas | 16 Weeks | Presence of microneuromas will be graded from In-Vivo Confocal Microscopy (IVCM) imaging |
| Asses change in dendritiform cells density by In-Vivo Confocal Microscopy (IVCM) imaging | 16 Weeks | Change in dendritiform cells density (in cells/mm\^2) of Corneal Immune Dendritiform Cells will be assesed via Via In-Vivo Confocal Microscopy (IVCM) imaging |
| Asses corneal sensitivity thresholds obtained with the Cochet Bonnet esthesiometer on 0-6 scale (in cm) | 16 Weeks | Corneal Sensitivity will be measured using a Cochet Bonnet aesthesiometer before the instillation of any dilating or anesthetic eye drops. Corneal sensitivity will be assessed in the qualifying NEI zones of each eye. This instrument is constituted by a retractable 6 cm length filament of 0.12 mm in diameter, and it is considered the gold standard for corneal sensation assessment. We will gently press the monofilament against the cornea, and we will shorten it in steps of 1.0 cm if a negative response is obtained. If a positive response is obtained, we will advance the monofilament by 0.5cm, and we will consider the corneal sensitivity as the longest filament length necessary to obtain a positive response. |
Countries
United States
Outcome results
None listed