REC 0/0559 Eye Drops for Treatment of Moderate and Severe Neurotrophic Keratitis in Adult Patients

Study Overview
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Brief Summary
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A phase 2 study, aiming to evaluate the efficacy, safety and pharmacokinetics of REC 0/0559 in treatment of Neurotrophic Keratitis in Adult Patient in Europe and United States of America.

Official Title
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Efficacy, Safety and Pharmacokinetics of 3 Doses of REC 0/0559 Eye Drops for the Treatment of Stage 2 (Moderate) and 3 (Severe) Neurotrophic Keratitis in Adult Patients

Conditions
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Neurotrophic Keratitis

Intervention / Treatment
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* Drug: Udonitrectag
* Other: Vehicle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have read, understood, and signed the informed consent form (ICF). Be a male or female aged ≥18 years at the time of ICF signature. Have stage 2 moderate (PED) or stage 3 severe (corneal ulcer) NK involving only 1 eye (study eye) and of at least 2 weeks duration. Patients with Stage 1 NK in the fellow eye can be enrolled. for the study eye Have no objective clinical evidence of improvement in the PED or corneal ulceration within the 2 weeks before the screening visit despite use of conventional non-surgical treatment (eg, nonpreserved ocular lubricants, nonpreserved topical antibiotics, oral doxycycline, patching, serum tears, and/or therapeutic contact lenses) as determined by the investigator's or referring physician's medical record. Have decreased corneal sensitivity (≤ 4 cm using the Cochet-Bonnet aesthesiometer) within the area of the PED or corneal ulcer and outside of the area of the defect in at least one corneal quadrant. Have a BCDVA score ≤ 75 ETDRS letters in the study eye, due to NK. Exclusion Criteria: Have participated in any clinical trial with an investigational drug/device within 2 months before the Screening Visit and throughout the study duration. Have a known hypersensitivity to one of the components of the study drug or procedural medications (eg, fluorescein), including to a compound chemically related to MT8 Have a presence or history of any ocular or systemic disorder or condition that might hinder the efficacy of the study treatment or its evaluation, could possibly interfere with the interpretation of study results, or could be judged by the investigator to be incompatible with the study visit schedule or conduct (eg, progressive or degenerative corneal or retinal conditions, lagophthalmos, uveitis, optic neuritis, poorly controlled diabetes, autoimmune disease, systemic infection, neoplastic diseases), or that may compromise the safety of the patient. Have a significant history of alcohol abuse or drug/solvent abuse Be unwilling to comply with any study assessments or procedures. Be a woman who is pregnant, nursing or planning a pregnancy. Be a woman of childbearing potential not using a highly effective method of birth control. Be a male patient who is not permanently sterile and who is not willing to use condoms during the study and for 4 weeks after the end of study treatment. For the study eye: Have any active ocular infection (bacterial, viral, fungal or protozoal) or active inflammation not related to NK in the study eye. Have any other ocular disease requiring topical ocular treatment in the study eye during the course of the study treatment period, except for glaucoma if treated by preservative-free eye drop (single-agent treatment, once daily, stable regimen 4 weeks before screening and during the study), Receive topical ophthalmological treatments other than the study drug provided by the study Sponsor and the treatments allowed by the study protocol (eg, preservative-free artificial tears; preservative-free eye drop (single-agent treatment, once daily, stable regimen 4 weeks before screening and during the study) for glaucoma; topical antibiotics; other than tetracycline). Have severe blepharitis and/or severe meibomian gland disease in the study eye. Have severe vision loss in the study eye with no potential for visual improvement in the opinion of the investigator as a result of the study treatment. Have evidence of corneal ulceration/melting involving the posterior third of the corneal stroma, or perforation in the study eye. Have a history of any ocular surgery (including laser or refractive surgical procedures) within 3 months before the Screening Visit in the study eye. An exception to the preceding statement will be allowed if the ocular surgery is considered to be the cause of the Stage 2 or 3 NK. Have a history of corneal transplantation in the study eye, except if performed to treat NK and at least 6 months prior screening. Have had prior surgical procedures for the treatment of NK (eg, tarsorrhaphy, conjunctival flap, etc.) except AMT, if at least 2 wks after the membrane has disappeared within the area of the PED or corneal ulcer (and at least 6 weeks after the procedure) in the study eye. Use therapeutic contact lenses or wear contact lenses for refractive correction during the study treatment periods in the eye(s) with NK. Have an anticipated need for punctal occlusion during the study treatment period. Patients with punctal occlusion or punctal plugs inserted before the study are eligible for enrolment provided that the punctal occlusion is maintained during the study. Have an uncontrolled glaucoma at the Screening Visit. (Patients suffering from glaucoma requiring ophthalmic drops for topical treatment at the Screening Visit or during the study are not eligible, except if the ophthalmic drops is a preservative-free treatment administered maximum once daily as a single-agent treatment and at a stable regimen 4 weeks before screening and at the same dose during the study. Patients treated with oral intraocular pressure-lowering drugs at the Screening Visit and during the study may be enrolled if their glaucoma status is assessed as stable and controlled. For the fellow eye Have Stage 2 or 3 NK or perforation. For any eye: Have a history of ocular cancer. Have had prior treatment with Oxervate™

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: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: The study will have an initial period of dose escalation followed by a parallel recruitment period. Randomisation in the first 24 patients will be sequential and after, patients will be randomised to all 4 treatment arms.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose 1 - 0.5 µg/day<br>Dose of study drug per day: 0.5 µg/day Study drug concentration: 5 µg/mL MT8 given 1 drop QID | Drug: Udonitrectag<br>* Eye drop solution in single dose unit.<br>Other: Vehicle<br>* Eye drop solution with no active substance in single dose unit.<br>|
| Experimental: Dose 2 - 2.5 µg/day<br>Dose of study drug per day: 2.5 µg/day Study drug concentration: 25 µg/mL MT8 given 1 drop QID | Drug: Udonitrectag<br>* Eye drop solution in single dose unit.<br>Other: Vehicle<br>* Eye drop solution with no active substance in single dose unit.<br>|
| Experimental: Dose 3 - 5 µg/day<br>Dose of study drug per day: 5 µg/day Study drug concentration: 50 µg/mL MT8 given 1 drop QID | Drug: Udonitrectag<br>* Eye drop solution in single dose unit.<br>Other: Vehicle<br>* Eye drop solution with no active substance in single dose unit.<br>|
| Placebo Comparator: Vehicle<br>Dose of study drug per day: 0 µg/day Study drug concentration: Vehicle given 1 drop QID | Other: Vehicle<br>* Eye drop solution with no active substance in single dose unit.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Corneal healing | The primary endpoint of this study is the percentage of patients achieving complete corneal healing of PED or corneal ulcer at Week 8, defined as no corneal fluorescein staining in the area of the PED or corneal ulcer as assessed by an independent central reading centre. | At week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual acuity | • Percentage of patients who achieve a 5-, 10-, and 15-letter mean improvement in best corrected distance visual acuity (BCDVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) chart at Week 8 compared to baseline (in all patients and in patients with a central location of the PED or corneal ulcer, respectively). | At week 8 |