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Study ended early to expedite development and enable earlier FDA discussions. Prior Phase 2 data (240 patients) showed favorable safety and placebo-like tolerability. Closure was not due to safety concerns.
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| Name | Class |
|---|---|
| Tufts Medical Center | OTHER |
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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: 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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A | Experimental | OK-101, 0.05% - one drop of study drug (0.05%) will be instilled in affected eye(s), four times daily (every 4 hours up to 16 hours, e.g., 9:00 am, 01:00 pm; 05:00 pm, 09:00pm) for 12 weeks |
|
| Arm B | Experimental | OK-101, 0.1% - one drop of study drug (0.1%) will be instilled in affected eye(s), four times daily (every 4 hours up to 16 hours, e.g., 9:00 am, 01:00 pm; 05:00 pm, 09:00pm) for 12 weeks. |
|
| Arm C | Placebo Comparator | Placebo - one drop of placebo will be instilled in affected eye(s), four times daily (every 4 hours up to 16 hours, e.g., 9:00 am, 01:00 pm; 05:00 pm, 09:00pm) for 12 weeks. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| OK-101 0.05% | Drug | 0.05% Ophthalmic Solution |
| |
| OK-101 0.1% |
| Measure | Description | Time Frame |
|---|---|---|
| Assess ocular pain using 0-10 visual analog scale (VAS) | 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. | 16 Weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Ocular Pain Assessment Survey (OPAS) scores | Twenty-seven item questionnaires specifically designed to assess symptoms and quality of life in ocular pain. | 16 Weeks |
| Ocular Surface Disease Index (OSDI©) scores |
| Measure | Description | Time Frame |
|---|---|---|
| Asses corneal sensitivity thresholds obtained with the Cochet Bonnet esthesiometer on 0-6 scale (in cm) | 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. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Pedram Hamrah, MD | Tufts Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Tufts Medical Center | Boston | Massachusetts | 02111 | United States |
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| ID | Term |
|---|---|
| D009437 | Neuralgia |
| ID | Term |
|---|---|
| D010523 | Peripheral Nervous System Diseases |
| D009468 | Neuromuscular Diseases |
| D009422 | Nervous System Diseases |
| D010146 | Pain |
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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).
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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.
| Drug |
0.1% Ophthalmic Solution |
|
| Placebo | Drug | Placebo |
|
Twelve-item questionnaire to assess symptoms of ocular irritation consistent with dry eye and their impact on vision-related functioning.
| 16 Weeks |
| QoL Improvement assesed by OPAS score | Twenty-seven item questionnaires specifically designed to assess symptoms and quality of life in ocular pain | 16 Weeks |
| Drop comfort Scores | Drop Comfort will be assesed using Scale 0-10, with a value of 0 being most comfortable and 10 being least comfortable. | 16 Weeks |
| 16 Weeks |
| Asses corneal nerve regeneration by measuring change in total length of corneal nerve regeneration | Change in total length of all nerves within an image (in mm/mm2) will be evaulated via In-Vivo Confocal Microscopy (IVCM) imaging | 16 Weeks |
| Assess change in numbers of microneuromas | Presence of microneuromas will be graded from In-Vivo Confocal Microscopy (IVCM) imaging | 16 Weeks |
| Asses change in dendritiform cells density by In-Vivo Confocal Microscopy (IVCM) imaging | 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 | 16 Weeks |
| D009461 |
| Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |