A clinical trial to evaluate the safety and the efficacy of NEXAGON ® (Lufepirsen Ophthalmic Gel) in subjects with Persistent Corneal Epithelial Defects (NEXPEDE-1)

Phase 2

Recruiting

• Conditions: Persistent Corneal Epithelial Defects
• Interventions: Drug: lufepirsen high dose; Drug: Vehicle; Drug: lufepirsen low dose

• Registration Number: 2023-507030-24-00
• Lead Sponsor: Glaukos Corporation

Brief Summary

To evaluate the safety and efficacy of NEXAGON compared to the NEXAGON vehicle (vehicle) in corneal re-epithelialization that is maintained for a minimum of 28 days in those subjects with persistent corneal epithelial defects as assessed by a central reading center (CRC) through the standardized assessment of digital images of fluorescein staining of the cornea/PCED

Detailed Description

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.

Study Timeline

• Study First Submitted: 2023-06-20
• Study First Submitted QC: 2023-07-21
• Study First Posted: 2023-07-28
• Study Start: 2023-08-17
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-21
• Last Update Posted: 2025-07-24
• Primary Completion: 2025-12
• Study Completion: 2025-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Not specified
• Target Recruitment: 60

Inclusion Criteria

male or female •Who are at least 2 years of age (US only) • Who are at least 18 years of age (all other countries)

the presence of a corneal epithelial defect that is at least 2 weeks in duration and refractory to one or more conventional non-surgical standard of care (SOC) treatments, as assessed by the Investigator

must have no clinical evidence of improvement in corneal epithelial defect within 2 weeks prior to randomization despite the use of non-surgical SOC treatment, as assessed by the Investigator

an epithelial defect measuring at least 1 mm along the largest diameter at Day 1 of the Treatment Period

subjects or their legally authorized representative(s) must have the ability to provide written informed consent, and must do so, prior to participation in any study-related procedures

female subjects with childbearing potential must be 1-year postmenopausal, surgically sterilized, or have a negative urine pregnancy test at Visit 1 and 2; women of childbearing potential must use an acceptable form of contraception throughout the study. Adequate birth control methods, including but not limited to, abstinence, stabilized on hormonal contraception [i.e., a) oral or patch/transdermal contraceptives for at least one full cycle (e.g., one or two months), or b) implant, injection, vaginal ring (e.g., NuvaRing®) for at least one week, intrauterine device (IUD) for at least one week, condom and a spermicidal, diaphragm and a spermicidal, or sterile solitary partner (vasectomy performed at least six months prior)

must have the ability and willingness to comply with all study procedures

Exclusion Criteria

any known ocular infection(s) that are deemed to be active (bacterial, viral, fungal and/or protozoal) requiring therapeutic intervention at the time of randomization in the affected eye(s)

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 table below are prohibited in the study.

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

evidence of corneal ulceration/melting involving the posterior third of the stroma and/or perforation in either eye

blepharitis or meibomian gland disease in the study eye that is deemed to be clinically relevant and/or active (i.e., requiring mechanical lid hygiene ≥ once a week or systemic treatment for blepharitis associated with MGD)

history of a full thickness keratoplasty, anterior lamellar keratoplasty (ALK), deep anterior lamellar keratoplasty (DALK), or more than 1 Descemet membrane endothelial keratoplasty (DMEK) or Descemet’s stripping endothelial keratoplasty (DSEK) procedure

history of ocular surgery or any ocular procedure(s) not meeting the designated washout time prior to Day 1 of the study

any other ocular disease requiring topical ocular medication in the affected eye during the course of the study treatment period

a Schirmer I test result (without anesthesia) of ≤ 3 mm/5 minutes in the study eye

a presence or history of any ocular or systemic disorder or condition that could interfere with the safety or efficacy of the study treatment, or the interpretation of the study results. Such degenerative and/or progressing ocular or systemic disorders are, but not limited to: lagophthalmos, uveitis, optic neuritis, poorly controlled diabetes, autoimmune disease, active systemic infection, neoplastic diseases

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
NEXAGON® (lufepirsen ophthalmic gel) High Dose Concentration	lufepirsen high dose	Lufepirsen (High dose concentration) applied topically to the eye once a week for a minimum of 4 weeks to a maximum of 8 weeks.
NEXAGON Vehicle (ophthalmic gel)	Vehicle	Vehicle applied topically to the eye once a week for a minimum of 4 weeks to a maximum of 8 weeks.
NEXAGON® (lufepirsen ophthalmic gel) Low Dose Concentration (EU sites only)	lufepirsen low dose	Lufepirsen (Low dose concentration) applied topically to the eye once a week for a minimum of 4 weeks to a maximum of 8 weeks. (EU sites only).

Primary Outcome Measures

Name	Time	Method
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 CRC. [EOS]		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 CRC. [EOS]

Secondary Outcome Measures

Name	Time	Method
Safety: • TEAEs [All visits] • Vital signs (blood pressure, pulse) [EOT, ET] • Clinical laboratory testing (hematology, serum chemistry, and urinalysis) [EOT, ET] • Ocular pain assessment (FACES) [All visits] • Visual acuity (ETDRS BCDVA) [All visits] • Slit lamp examination [All visits] • NEI grading scale for corneal fluorescein staining [All visits] • Dilated fundus ophthalmoscopy [EOS, ET]		Safety: • TEAEs [All visits] • Vital signs (blood pressure, pulse) [EOT, ET] • Clinical laboratory testing (hematology, serum chemistry, and urinalysis) [EOT, ET] • Ocular pain assessment (FACES) [All visits] • Visual acuity (ETDRS BCDVA) [All visits] • Slit lamp examination [All visits] • NEI grading scale for corneal fluorescein staining [All visits] • Dilated fundus ophthalmoscopy [EOS, ET]
Efficacy: • 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. [EOS] • The proportion of subjects achieving corneal re-epithelialization, based on assessment of corneal fluorescein staining images of the PCED by a CRC. [EOT]		Efficacy: • 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. [EOS] • The proportion of subjects achieving corneal re-epithelialization, based on assessment of corneal fluorescein staining images of the PCED by a CRC. [EOT]
Efficacy: • The proportion of subjects achieving corneal re-epithelialization based on assessment of corneal fluorescein staining images of the PCED by Investigator. [EOT] • 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. [EOS]		Efficacy: • The proportion of subjects achieving corneal re-epithelialization based on assessment of corneal fluorescein staining images of the PCED by Investigator. [EOT] • 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. [EOS]
Efficacy: • 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. [EOS]		Efficacy: • 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. [EOS]
Efficacy: • 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. [All visits]. • 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. [All visits].		Efficacy: • 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. [All visits]. • 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. [All visits].
Efficacy • The mean change from baseline (CFB) in ocular pain based on OPAS. [EOS] • The mean CFB in BCDVA (ETDRS). [EOS] • The proportion of subjects who achieve a 15 letter (ETDRS) gain in BCDVA. [EOS] • The proportion of subjects requiring open-label treatment during the Treatment Period. [EOT]		Efficacy • The mean change from baseline (CFB) in ocular pain based on OPAS. [EOS] • The mean CFB in BCDVA (ETDRS). [EOS] • The proportion of subjects who achieve a 15 letter (ETDRS) gain in BCDVA. [EOS] • The proportion of subjects requiring open-label treatment during the Treatment Period. [EOT]
Efficacy • 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. [Open-Label EOS]		Efficacy • 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. [Open-Label EOS]
Exploratory: • The mean percentage CFB in corneal neuronal sensitivity. [EOS] • The evaluation of the CFB in MMP-9 levels in subjects tear fluid. [EOS] • The portion of subjects who experience loss of epithelium due to the removal of the bandage contact lens (BCL). [All visits]		Exploratory: • The mean percentage CFB in corneal neuronal sensitivity. [EOS] • The evaluation of the CFB in MMP-9 levels in subjects tear fluid. [EOS] • The portion of subjects who experience loss of epithelium due to the removal of the bandage contact lens (BCL). [All visits]

Trial Locations

Locations (2)

Glaukos Investigative Site; 🇪🇸 Zaragoza, Spain

Glaukos investigative Site; 🇮🇹 Messina, Italy