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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Glaukos Corp.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11]

Trial duration

30 Apr 2025 → ongoing

Decision date (initial)

2024-04-05

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Glaukos Corporation

External identifiers

EU CT number

2023-507030-24-00

ClinicalTrials.gov

NCT05966493

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

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

Secondary objectives 3

1. Safety: • Treatment-emergent adverse events (TEAEs) • Vital signs (blood pressure, pulse) • Clinical laboratory tests o Hematology, serum chemistry, and urinalysis o Hemoglobin A1c (HbA1c) (diabetic status) • Patient-reported outcome measures (ocular pain) • Visual acuity • Slit lamp biomicroscopy • National Eye Instituto (NEI) grading scale for corneal fluorescein staining • Dilated fundus ophthalmoscopy
2. Efficacy: • Corneal re-epithelialization that is maintained for a minimum of 28 days in subjects, as assessed by the Investigator through the standardized evaluation of fluorescein staining of the PCED by slit lamp biomicroscopy. • Comparison of the number of dose administrations subjects received to achieve corneal re-epithelialization that is maintained for a minimum of 28 days, as assessed by a CRC through the standardized evaluation of digital images of the PCED stained with fluorescein. • Comparison of the number of dose administrations subjects received to achieve corneal re-epithelialization that is maintained for a minimum of 28 days, as assessed by the Investigator through the standardized assessment of fluorescein staining of the PCED by slit lamp biomicroscopy. • Time (in days) to achieve corneal re-epithelialization as assessed by a CRC through the standardized evaluation of digital images of the PCED stained with fluorescein. • Time (in days) to achieve corneal re-epithelialization as measured by the Investigator utilizing the standardized assessment of fluorescein staining of the PCED by slit lamp biomicroscopy. • Occurrence and severity of ocular pain as assessed by administration of the Ocular Pain Assessment Survey (OPAS). • Change in best-corrected distance visual acuity (BCDVA) using the Early Treatment of Diabetic Retinopathy Study (ETDRS). • Determination of the optimal effective dose concentration of NEXAGON
3. Exploratory: • Change(s) in corneal sensitivity. • Changes in aqueous matrix metalloproteinase 9 (MMP-9) levels in subjects corneal tear fluid.

Conditions and MedDRA coding

Persistent Corneal Epithelial Defects

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. male or female •Who are at least 2 years of age (US only) • Who are at least 18 years of age (all other countries)
2. 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
3. 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
4. an epithelial defect measuring at least 1 mm along the largest diameter at Day 1 of the Treatment Period
5. 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
6. 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)
7. must have the ability and willingness to comply with all study procedures

Exclusion criteria 12

1. 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)
2. 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
3. evidence of corneal ulceration/melting involving the posterior third of the stroma and/or perforation in either eye
4. 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)
5. 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
6. history of ocular surgery or any ocular procedure(s) not meeting the designated washout time prior to Day 1 of the study
7. any other ocular disease requiring topical ocular medication in the affected eye during the course of the study treatment period
8. a Schirmer I test result (without anesthesia) of ≤ 3 mm/5 minutes in the study eye
9. 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
10. a known hypersensitivity to one of the components of the study or procedural medications (e.g., NEXAGON, fluorescein)
11. participated in an interventional clinical drug or device trial within 28 days prior to Day 1
12. use of the medications presented in the table below are prohibited in the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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 endpoints 8

1. 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]
2. 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]
3. 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]
4. 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]
5. 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].
6. 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]
7. 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]
8. 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]

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Glaukos Corp.

Sponsor organisation

Glaukos Corp.

Address

1 Glaukos Way

City

Aliso Viejo

Postcode

92656-2704

Country

United States

Scientific contact point

Organisation

Glaukos Corp.

Contact name

Chief Development Officer

Public contact point

Organisation

Glaukos Corp.

Contact name

Vice President Clinical Research

Third parties 11

Locations

3 EU/EEA countries · 15 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 27 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications