Lufepirsen Eye Gel for Corneal Ulcer

(NEXPEDE-1 Trial)

Recruiting at 34 trial locations

Overseen By Study Director

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Glaukos Corporation

Disqualifiers: Ocular infection, Corneal ulceration, Blepharitis, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 4-8 weeks

84 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new eye gel called NEXAGON® (Lufepirsen Ophthalmic Gel) to determine its effectiveness in healing corneal ulcers, which are persistent open sores on the eye that haven't responded to standard treatments. Researchers aim to assess the gel's safety and effectiveness for individuals with persistent corneal epithelial defects (PCED). Participants will receive either a low or high dose of the gel, or a placebo (a harmless substance with no active medicine), applied to the eye once a week for up to eight weeks. Individuals with a corneal ulcer lasting at least two weeks without improvement might be suitable for this study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it mentions that certain medications are prohibited. It's best to discuss your current medications with the trial team to see if any are not allowed.

Is there any evidence suggesting that NEXAGON® (lufepirsen ophthalmic gel) is likely to be safe for humans?

Research has shown that lufepirsen eye gel holds promise for patients with persistent corneal epithelial defects (PCED). In one study, about 66.7% of patients using lufepirsen experienced significant improvement in their eye condition, indicating that the treatment helped heal corneal defects in many cases.

Regarding safety, the treatment has generally been well-tolerated. In a study with 23 patients, the gel was used without major safety concerns, and no serious side effects were reported, suggesting it is fairly safe for humans. Ongoing research aims to confirm these safety findings and ensure the treatment's effectiveness for more patients.

As part of early trials, these findings are still being confirmed. However, the initial results are encouraging, indicating that lufepirsen eye gel could be a safe option for treating corneal issues. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for corneal ulcers, which typically involve antibiotics or antifungal medications, NEXAGON® (Lufepirsen Ophthalmic Gel) uses a novel approach by targeting the underlying mechanisms involved in wound healing. Researchers are excited about Lufepirsen because it works by modulating gene expression to promote faster and more effective healing of the corneal surface. This treatment is applied as a gel directly to the eye, which could lead to better adherence and comfort compared to traditional eye drops or ointments. The unique mechanism and delivery method offer potential advantages in both efficacy and patient experience, setting it apart from existing options.

What evidence suggests that NEXAGON® (lufepirsen ophthalmic gel) could be an effective treatment for corneal ulcer?

Research has shown that NEXAGON® (lufepirsen eye gel) may help treat persistent corneal epithelial defects (PCED), which are stubborn eye surface injuries. In one study, patients experienced about a 70% reduction in the size of their eye injuries, indicating significant healing potential. Previous patients tolerated the treatment well, suggesting it is safe. In this trial, participants will receive either a low or high dose concentration of NEXAGON® or a placebo comparator. These findings suggest that lufepirsen could be a promising option for those dealing with PCED. ^{1 2 3 4 5}

Who Is on the Research Team?

Luis G. Vargas, MD

Principal Investigator

Glaukos Corporation

Are You a Good Fit for This Trial?

This trial is for individuals with persistent corneal epithelial defects (PCED) lasting at least 2 weeks and unresponsive to standard treatments. Participants must not show improvement in the last 2 weeks despite treatment, be capable of consent, and if childbearing potential, not pregnant or sterilized. Exclusions include recent ocular surgery without proper washout time, other eye diseases requiring medication, active infections or history of certain keratoplasty procedures.

Inclusion Criteria

My condition has lasted 2 weeks and hasn't improved with standard treatments.

PCED measures at least 2 mm along the largest diameter

Subject must provide written informed consent (or assent)

Exclusion Criteria

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

I have an eyelid or tear gland condition that needs treatment.

I am not taking any medications that are not allowed in the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive NEXAGON or vehicle gel applied topically weekly for 4 to 8 weeks

4-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label Treatment

Participants whose defect has not re-epithelialized or failed to maintain re-epithelialization may enter an open-label treatment period for an additional 8 weeks

8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• NEXAGON® (Lufepirsen Ophthalmic Gel)

Trial Overview The study tests NEXAGON® (lufepirsen ophthalmic gel) against a placebo vehicle to assess its safety and effectiveness in treating PCED. Patients will be randomly assigned to receive either the experimental gel or a placebo while their health outcomes are monitored.

How Is the Trial Designed?

Group I: NEXAGON® (lufepirsen ophthalmic gel) Low Dose Concentration (EU sites only) Experimental Treatment 1 Intervention

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).

Group II: NEXAGON® (lufepirsen ophthalmic gel) High Dose Concentration Experimental Treatment 1 Intervention

Lufepirsen (High dose concentration) applied topically to the eye once a week for a minimum of 4 weeks to a maximum of 8 weeks.

Group III: NEXAGON Vehicle (ophthalmic gel) Placebo Group 1 Intervention

Vehicle applied topically to the eye once a week for a minimum of 4 weeks to a maximum of 8 weeks.

Who Is Running the Clinical Trial?

Glaukos Corporation

Lead Sponsor

Trials

69

Recruited

9,500+

Thomas Burns

Glaukos Corporation

Chief Executive Officer since 2002

B.A. from Yale University

Dr. Tomas Navratil

Glaukos Corporation

Chief Medical Officer since 2022

MD from Harvard Medical School

Amber Ophthalmics, Inc.

Lead Sponsor

Trials

2

Recruited

120+

Published Research Related to This Trial

A 62-year-old woman experienced corneal melting after using the topical anti-inflammatory medication Nepafenac, highlighting a potential safety concern with this drug.

The corneal melting resolved quickly after stopping Nepafenac, indicating that discontinuation of the medication can lead to recovery from this adverse effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case of corneal melting associated with the use of topical nepafenac. Bekendam, PD., Narváez, J., Agarwal, M.[2013]

The novel dorzolamide hydrochloride in situ gel nanoemulsion (NE) significantly improved ocular bioavailability and duration of action compared to traditional eye drops and marketed products, as shown in tests on normotensive albino rabbits.

The formulation, which included Poloxamer 407, demonstrated faster onset and prolonged effects, highlighting the effectiveness of the thermoreversible gel properties in enhancing the therapeutic efficacy of the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of dorzolamide hydrochloride in situ gel nanoemulsion for ocular delivery. Ammar, HO., Salama, HA., Ghorab, M., et al.[2012]

The developed thermosensitive in situ gelling ophthalmic drug delivery system, using poloxamer analogs and polycarbophil, effectively maintains drug concentration in the eye, improving bioavailability of betaxolol hydrochloride (BH).

In vivo studies showed that this formulation significantly reduced intraocular pressure (IOP), indicating its potential efficacy for treating conditions like glaucoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preparation, pharmacokinetics and pharmacodynamics of ophthalmic thermosensitive in situ hydrogel of betaxolol hydrochloride. Huang, W., Zhang, N., Hua, H., et al.[2022]

In vitro studies showed that common ophthalmic solutions significantly absorbed into Acuvue Oasys silicone hydrogel lenses, indicating potential concerns about drug and preservative accumulation.

However, in vivo results revealed that no active ingredients or preservatives were found on the lenses worn by patients, suggesting that the discomfort some users experience is not due to buildup on the lenses, which supports the safe use of these bandage lenses with eye drops.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro and in vivo effects of ophthalmic solutions on silicone hydrogel bandage lens material Senofilcon A. Erdal, NB., Adolfsson, KH., De Lima, S., et al.[2019]

The study identified formulation 1 (F1) using Poloxamer 188 at 5% concentration as the optimal in situ gel for ophthalmic use, with a pH of 6.45 and viscosity of 5.47 cP, indicating good stability and suitability for eye applications.

In situ gel technology enhances drug bioavailability and effectiveness compared to traditional ophthalmic preparations, addressing limitations of conventional delivery methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physical study of Chloramphenicol In Situ Gel with Base Hydroxypropyl Methylcellulose and Poloxamer 188. Kurniawansyah, IS., Gozali, D., Sopyan, I., et al.[2022]

The developed thermosensitive in situ gelling and mucoadhesive ophthalmic drug delivery system significantly improves the retention of puerarin in the eye compared to conventional solutions, allowing for a longer duration of drug action.

In vitro and in vivo studies showed that this new formulation not only maintains drug concentration effectively but also enhances ocular bioavailability, making it a promising option for treating eye conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of a poloxamer analogs/carbopol-based in situ gelling and mucoadhesive ophthalmic delivery system for puerarin. Qi, H., Chen, W., Huang, C., et al.[2016]

Bromfenac ophthalmic solution 0.09% significantly reduced pain in patients with corneal ulcers, with 52% of treated patients reporting no pain by day 3, compared to 0% in the control group.

The treatment also promoted faster healing of the corneal epithelium, with 68% of bromfenac-treated patients showing healing by day 20, while only 10% of controls healed in the same timeframe, and no adverse events were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of bromfenac for the treatment of corneal ulcer pain. Schechter, BA., Trattler, W.[2012]

In a study of 43 patients using senofilcon A contact lenses for therapeutic purposes, 81% of those fitted for pain relief reported full effectiveness, indicating strong efficacy in managing corneal pain.

The lenses also showed a 64% full effectiveness rate in improving corneal integrity, with no reported adverse events, highlighting their safety and effectiveness in protecting the cornea post-surgery and during recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Application of senofilcon a contact lenses for therapeutic bandage lens indications. Shafran, T., Gleason, W., Osborn Lorenz, K., et al.[2022]

In a study involving 60 patients with mild-to-moderate dry eye disease, the combination of trehalose 3% and hyaluronic acid 0.15% (TH) significantly increased tear film thickness (TFT) compared to other lubricant eye gels, particularly at 60 and 120 minutes after application.

All tested eye gels showed a notable increase in TFT 10 minutes post-application, but only the TH gel maintained a significant increase in TFT over time, suggesting it has a longer-lasting effect on tear film stability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of different lubricant eye gels on tear film thickness as measured with ultrahigh-resolution optical coherence tomography. Wozniak, PA., Schmidl, D., Bata, AM., et al.[2022]

The study developed a stable rhEGF/poloxamer gel that enhances the stability and delivery of rhEGF for ophthalmic use, showing improved retention in tear fluid compared to rhEGF solution.

The optimal formulation with a 1:20 ratio of rhEGF/HP-beta-CD complex demonstrated prolonged retention in the eye, suggesting it could be an effective method for delivering therapeutic agents to the ocular surface.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

rhEGF/HP-beta-CD complex in poloxamer gel for ophthalmic delivery. Kim, EY., Gao, ZG., Park, JS., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05966493

A Study to Evaluate the Safety and Efficacy of NEXAGON® ... This study is to evaluate the safety and efficacy of NEXAGON® (lufepirsen ophthalmic gel) (NEXAGON) in subjects with persistent corneal epithelial defects ...

2. ophth.wisc.edu ophth.wisc.edu/blog/2023/12/21/nexpede-1/

NEXPEDE-1 - Ophthalmology and Visual Sciences To evaluate the safety and efficacy of NEXAGON (lufepirsen ophthalmic gel) in subjects with persistent corneal epithelial defects (PCED).

3. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05966493/a-study-to-evaluate-the-safety-and-efficacy-of-nexagonr-lufepirsen-ophthalmic-gel-in-subjects-with-pced

A Study to Evaluate the Safety and Efficacy of NEXAGON® ... This study is to evaluate the safety and efficacy of NEXAGON® (lufepirsen ophthalmic gel) (NEXAGON) in subjects with persistent corneal epithelial defects ( ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12015846/

Emerging Treatments for Persistent Corneal Epithelial Defects A prospective study reported approximately a 70% reduction in defect size among 23 patients with PCEDs [41]. Similarly, a prospective case series on 10 patients ...

5. iovs.arvojournals.org iovs.arvojournals.org/article.aspx?articleid=2787979

A Phase 2, randomized, prospective, double-masked ... - IOVS Results : Subjects with ages ranging from 7 to 75 years had a mean baseline corneal defect area of 46.67 mm2 (4 to 176 mm2). Treatment was well tolerated, with ...