LUFEPIRSEN for Persistent corneal epithelial defect

Inclusion criteria

• {"criterion_text":"- male or female •Who are at least 2 years of age (US only) • Who are at least 18 years of age (all other countries)\n- 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\n- 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\n- an epithelial defect measuring at least 1 mm along the largest diameter at Day 1 of the Treatment Period\n- 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\n- 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)\n- must have the ability and willingness to comply with all study procedures"}

Exclusion criteria

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

Primary endpoints

• {"endpoint_text":"- 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]","definition_or_measurement_approach":"Assessment based on corneal fluorescein staining images of the PCED reviewed by a central reading center (CRC); endpoint measured as proportion of subjects with re-epithelialization maintained for minimum 28 days. [EOS]"}

Secondary endpoints

• {"endpoint_text":"- 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]","definition_or_measurement_approach":"Safety assessments collected at specified visits: TEAEs at all visits; vitals at EOT/ET; labs at EOT/ET; ocular pain by FACES at all visits; visual acuity by ETDRS BCDVA at all visits; slit lamp and NEI grading at all visits; dilated fundus ophthalmoscopy at EOS/ET."}
• {"endpoint_text":"- 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]","definition_or_measurement_approach":"Investigator assessment by slit lamp biomicroscopy with fluorescein staining (EOS) and CRC assessment of digital images (EOT) for proportion re-epithelialized."}
• {"endpoint_text":"- 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]","definition_or_measurement_approach":"Investigator image-based assessment at EOT; CRC-reviewed image count of dose administrations required for durable re-epithelialization (EOS)."}
• {"endpoint_text":"- 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]","definition_or_measurement_approach":"Investigator assessment of number of dose administrations required to achieve durable re-epithelialization, based on fluorescein-stained images (EOS)."}
• {"endpoint_text":"- 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].","definition_or_measurement_approach":"Time-to-event endpoints measured in days from randomization to re-epithelialization by CRC image assessment and Investigator assessment at all visits."}
• {"endpoint_text":"- 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]","definition_or_measurement_approach":"Mean change from baseline in OPAS (ocular pain) and ETDRS BCDVA at EOS; proportion achieving ≥15-letter ETDRS gain at EOS; proportion requiring open-label treatment during treatment period (EOT)."}
• {"endpoint_text":"- 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]","definition_or_measurement_approach":"CRC assessment of images in the open-label treatment period; proportion achieving durable re-epithelialization for ≥28 days (open-label EOS)."}

Other endpoints

• {"endpoint_text":"- 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]\n- 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]","definition_or_measurement_approach":"Open-label CRC image assessment for durability endpoint; exploratory measures include percentage change from baseline in corneal neuronal sensitivity (mean), change from baseline in tear MMP-9 levels, and proportion with epithelial loss due to bandage contact lens removal (assessed at all visits)."}

Italy

Earliest CTIS Part Ii Submission Date

28-02-2024

Latest Decision Or Authorization Date

04-04-2025

Processing Time Days

401

Number Of Sites

4

Number Of Participants

20

Germany

Earliest CTIS Part Ii Submission Date

11-03-2024

Latest Decision Or Authorization Date

29-01-2026

Processing Time Days

689

Number Of Sites

5

Number Of Participants

20

Spain

Earliest CTIS Part Ii Submission Date

25-03-2024

Latest Decision Or Authorization Date

26-01-2026

Processing Time Days

672

Number Of Sites

7

Number Of Participants

20

Primary sponsor

Full Name

Glaukos Corp.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

SDC, Statistics and Data Corporation

Responsibilities

code 6

Name

Lexitas Pharma Services, Inc.

Responsibilities

code 5

Name

PCI Pharma Services

Responsibilities

code 14

Name

PCI Pharma Services Germany GmbH

Responsibilities

code 14

Name

Millmount Healthcare Limited

Responsibilities

code 14

Third parties

• {"country":"United States","full_name":"Drug Safety Navigator LLC","duties_or_roles":"pharmacovigilance services; code 8","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Spain","full_name":"Craplatform S.L.","duties_or_roles":"codes: 12,2,5","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"PCI Pharma Services Germany GmbH","duties_or_roles":"code 14","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Acm Medical Laboratory Inc.","duties_or_roles":"code 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"SDC, Statistics and Data Corporation","duties_or_roles":"code 6","organisation_type":"Industry"}
• {"country":"United States","full_name":"Lexitas Pharma Services, Inc.","duties_or_roles":"code 5","organisation_type":"Industry"}
• {"country":"Ireland","full_name":"Millmount Healthcare Limited","duties_or_roles":"code 14","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Curia Bio California Inc.","duties_or_roles":"Drug Product Manufacturer","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Acm Global Central Laboratory Limited","duties_or_roles":"code 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Nitto Denko Avecia Inc.","duties_or_roles":"Drug Substance Manufacturer","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"PCI Pharma Services","duties_or_roles":"code 14","organisation_type":"Industry"}