Lufepirsen Eye Gel for Corneal Ulcer

(NEXPEDE-1 Trial)

Recruiting in Palo Alto (17 mi)

+6 other locations

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Amber Ophthalmics, Inc.

Disqualifiers: Ocular infection, Corneal ulceration, Blepharitis, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing NEXAGON, an eye gel, on patients with persistent eye surface wounds that don't heal with usual treatments. The gel helps the eye's surface cells grow back and heal the wound.

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.

What data supports the effectiveness of the drug Lufepirsen Eye Gel for treating corneal ulcers?

Research on similar gel-based eye treatments, like those using poloxamer, shows that they can improve how long a drug stays on the eye and how well it works. This suggests that Lufepirsen Eye Gel might also be effective in treating corneal ulcers by staying on the eye longer and delivering the drug more effectively. ^{1 2 3 4 5}

How is the drug Lufepirsen Eye Gel unique for treating corneal ulcers?

Lufepirsen Eye Gel is unique because it uses a gel formulation that can adhere to the eye's surface, potentially allowing for prolonged drug retention and effectiveness compared to standard liquid eye drops, which often wash away quickly. ^{6 7 8 9 10}

Research Team

Eligibility Criteria

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.

My condition hasn't improved in 2 weeks despite standard treatments.

PCED measures at least 2 mm along the largest diameter

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.

Trial Timeline

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

Treatment Details

Interventions

• NEXAGON® (Lufepirsen Ophthalmic Gel) (Monoclonal Antibodies)

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.

Participant Groups

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

Lufepirsen (High dose concentration) applied topically weekly for 4 to 8 weeks.

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

Vehicle applied topically weekly for 4 to 8 weeks.

Who Is Running the Clinical Trial?

Amber Ophthalmics, Inc.

Lead Sponsor

Trials

2

Recruited

120+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Development of dorzolamide hydrochloride in situ gel nanoemulsion for ocular delivery. [2012]

2. France pubmed.ncbi.nlm.nih.gov

Preparation, pharmacokinetics and pharmacodynamics of ophthalmic thermosensitive in situ hydrogel of betaxolol hydrochloride. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

In vitro and in vivo effects of ophthalmic solutions on silicone hydrogel bandage lens material Senofilcon A. [2019]

4. India pubmed.ncbi.nlm.nih.gov

Physical study of Chloramphenicol In Situ Gel with Base Hydroxypropyl Methylcellulose and Poloxamer 188. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Application of senofilcon a contact lenses for therapeutic bandage lens indications. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Development of a poloxamer analogs/carbopol-based in situ gelling and mucoadhesive ophthalmic delivery system for puerarin. [2016]

7. United States pubmed.ncbi.nlm.nih.gov

Case of corneal melting associated with the use of topical nepafenac. [2013]

8. England pubmed.ncbi.nlm.nih.gov

Effect of different lubricant eye gels on tear film thickness as measured with ultrahigh-resolution optical coherence tomography. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of bromfenac for the treatment of corneal ulcer pain. [2012]

10. Netherlands pubmed.ncbi.nlm.nih.gov

rhEGF/HP-beta-CD complex in poloxamer gel for ophthalmic delivery. [2019]