A Study to Evaluate the Safety and Efficacy of NEXAGON® (Lufepirsen Ophthalmic Gel) in Subjects With PCED

Study Overview
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Brief Summary
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This study is to evaluate the safety and efficacy of NEXAGON® (lufepirsen ophthalmic gel) (NEXAGON) in subjects with persistent corneal epithelial defects (PCED). The objectives of the study are to evaluate the safety and efficacy of NEXAGON in this population.

Detailed Description
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This study is a randomized, multicenter, double-masked, vehicle-controlled study to evaluate the safety and efficacy of NEXAGON (lufepirsen ophthalmic gel) in subjects with persistent corneal epithelial defects (PCED). The study will enroll subjects who will complete a Screening Period, Treatment Period (up to 8 weeks) and Follow-up Period (4 weeks). Those subjects whose defect has not re-epithelialized by the completion of the Treatment Period or who achieved re-epithelialization but failed to maintain re-epithelialization for 28 days after treatment completion (durability) are eligible to enter the NEXAGON Open-label Treatment Period for an additional 8 weeks.

Official Title
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A Randomized, Multicenter, Double-Masked, Vehicle-Controlled Phase 2/3 Study to Evaluate the Safety and Efficacy of NEXAGON® (Lufepirsen Ophthalmic Gel) in Subjects With Persistent Corneal Epithelial Defects (NEXPEDE-1)

Conditions
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Persistent Corneal Epithelial Defect

Intervention / Treatment
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* Drug: lufepirsen
* Drug: Vehicle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a PCED that is at least 2 weeks in duration and refractory to one or more conventional non-surgical standard of care (SOC) treatments Have no clinical evidence of improvement in the PCED within 2 weeks prior to randomization despite the use of non-surgical SOC treatment PCED measures at least 2 mm along the largest diameter Subject must provide written informed consent (or assent) Subjects with childbearing potential must be 1-year postmenopausal, surgically sterilized, or have a negative urine pregnancy test Exclusion Criteria: Have a known ocular infection that is deemed to be active requiring therapeutic intervention Present with a corneal surface defect in either eye that is directly attributed to an infectious etiology (bacterial, viral, fungal and/or protozoal) that has not fully resolved and/or treatment has not been completed Present with evidence of corneal ulceration/melting involving the posterior third of the stroma and/or perforation in either eye Have a blepharitis or meibomian gland disease in the study eye that in the opinion of the Investigator is deemed to be clinically relevant and/or active Have a history of a full thickness keratoplasty, > 1 Descemet membrane endothelial keratoplasty (DMEK) or Descemet's stripping endothelial keratoplasty (DSEK) procedure Have a history of ocular surgery or any ocular procedure(s) not meeting the designated washout time Have any other ocular disease requiring topical ocular medication in the affected eye A Schirmer I test result (without anesthesia) of ≤ 3 mm/5 minutes in the study eye Have a presence or history of any ocular or systemic disorder or condition that, in the judgement of the Investigator, might hinder the efficacy of the study treatment or its evaluation, could possibly interfere with the interpretation of study results, or could be incompatible with the study visit schedule or conduct Have a known hypersensitivity to one of the components of the study or procedural medications (e.g., NEXAGON, fluorescein) Participated in an interventional clinical drug or device trial within 28 days prior to Day 1 Use of the medications presented in the protocol that are prohibited in the study. Use of Oxervate within 30 days of study enrollment.

Ages Eligible for Study
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Minimum Age: 2 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NEXAGON® (lufepirsen ophthalmic gel) High Dose Concentration<br>Lufepirsen (High dose concentration) applied topically weekly for 4 to 8 weeks. | Drug: lufepirsen<br>* Lufepirsen is an unmodified connexin43 antisense oligonucleotide.<br>* Other names: NEXAGON®;|
| Experimental: NEXAGON® (lufepirsen ophthalmic gel) Low Dose Concentration<br>Lufepirsen (Low dose concentration) applied topically weekly for 4 to 8 weeks. | Drug: lufepirsen<br>* Lufepirsen is an unmodified connexin43 antisense oligonucleotide.<br>* Other names: NEXAGON®;|
| Placebo Comparator: NEXAGON Vehicle (ophthalmic gel)<br>Vehicle applied topically weekly for 4 to 8 weeks. | Drug: Vehicle<br>* Matching vehicle without lufepirsen.<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Achieve Corneal Re-epithelialization Including Durability (CRC) | The proportion of subjects achieving corneal re-epithelialization that is maintained for a minimum of 28 days, based on assessment of corneal fluorescein staining images of the PCED by a Central Reading Center (CRC). | End of Study: 28 Days after achieving re-epithelialization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Achieve Corneal Re-epithelialization Including Durability (Investigator) | The proportion of subjects achieving corneal re-epithelialization that is maintained for a minimum of 28 days, based on assessment of corneal fluorescein staining of the PCED by the Investigator | End of Study: 28 Days after achieving re-epithelialization | 
| Achieve Corneal Re-epithelialization (CRC) | The proportion of subjects achieving corneal re-epithelialization, based on assessment of corneal fluorescein staining images of the PCED by a CRC. | Weeks 1, 2, 3, 4, 5, 6, 7, 8 | 
| Achieve Corneal Re-epithelialization (Investigator) | The proportion of subjects achieving corneal re-epithelialization based on assessment of corneal fluorescein staining images of the PCED by Investigator. | Weeks 1, 2, 3, 4, 5, 6, 7, 8 | 
| Number of Dose Administrations Required to Achieve Corneal Re-epithelialization (CRC) | The number of dose administrations subjects required to achieve corneal re-epithelialization that is maintained for a minimum of 28 days after completing treatment, based on assessment of corneal fluorescein staining images of the PCED by a CRC. | Weeks 1, 2, 3, 4, 5, 6, 7, 8 | 
| Number of Dose Administrations Required to Achieve Corneal Re-epithelialization (Investigator) | The number of dose administrations subjects required to achieve corneal re-epithelialization that is maintained for a minimum of 28 days after completing treatment, based on assessment of corneal fluorescein staining images of the PCED by Investigator. | Weeks 4, 5, 6, 7, 8 | 
| Time to Corneal Re-epithelialization (CRC) | The time (in days) to corneal re-epithelialization, defined as the time from randomization to the time of corneal re-epithelialization based on assessment of corneal fluorescein staining images of the PCED by a CRC. | Weeks 1, 2, 3, 4, 5, 6, 7, 8 | 
| Time to Corneal Re-epithelialization (Investigator) | The time (in days) to corneal re-epithelialization, defined as the time from randomization to the time of corneal re-epithelialization based on assessment of corneal fluorescein staining images of the PCED by Investigator. | Weeks 1, 2, 3, 4, 5, 6, 7, 8 | 
| Ocular Pain Assessment Survey | The mean change from baseline (CFB) in ocular pain based on Ocular Pain Assessment Survey (OPAS). | End of Study: Week 9, 10, 11, or 12 | 
| Assessment of visual health status indices by the administration of the NEI Visual Function Questionnaire (NEI-VFQ-25). | Assess the change from baseline in the subject's visual health status using the NEI-VFQ-25 (0-100, higher scores representing a better status). | End of Study: Week 9, 10, 11, or 12 | 
| Visual Acuity Assessment | The mean CFB in Best Corrected Distance Visual Acuity (BCDVA). | End of Study: Week 9, 10, 11, or 12 | 
| Visual Acuity Improvement | The proportion of subjects who achieve a 15 letter (ETDRS) gain in BCDVA. | End of Study: Week 9, 10, 11, or 12 | 
| Open-label Treatment Period | The proportion of subjects requiring open-label treatment during the Treatment Period. | Open-label Day 1 | 
| Achieve Corneal Re-epithelialization in Open-label Treatment Period | The proportion of subjects in the Open-Label Treatment Period that achieve re-epithelialization of the corneal epithelial defect that remains durable for a minimum of 28 days based on the CRC assessment on images. | End of Study: 28 Days after achieving re-epithelialization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PCED, Corneal Defect, PED