BRM424 Ophthalmic Solution for Neurotrophic Keratitis

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: BRIM Biotechnology Inc.

Disqualifiers: Active ocular infection, Contact lenses, Childbearing potential

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests an eye drop called BRM424 Ophthalmic Solution to evaluate its effectiveness and safety for individuals with neurotrophic keratitis (NK), a condition where nerve problems damage the eye's surface. The study examines two different doses of the eye drop for those with more advanced stages of NK, specifically Stage 2 (persistent epithelial defect) and Stage 3 (corneal ulcer). Suitable participants are those diagnosed with these stages of NK, without any other active eye infections or inflammation unrelated to NK. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that BRM424 Ophthalmic Solution is likely to be safe for humans?

Research has shown that BRM424 Eye Drops have promising safety results from early studies. BRM treatments, in general, are considered safe for children with eye conditions like uveitis, an inflammation of the eye, indicating they are well-tolerated. Tests on rabbits demonstrated that BRM424 is safe and effective, meeting strict safety standards. The current study is in the middle phase of trials, providing some safety data, but further testing is needed to confirm these findings in people. So far, no major safety issues have been reported. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for neurotrophic keratitis?

Researchers are excited about BRM424 Ophthalmic Solution for neurotrophic keratitis because it offers a potentially groundbreaking approach compared to current treatments like lubricating eye drops, therapeutic contact lenses, or surgery. Unlike these standard care options, BRM424 is designed to promote corneal healing by targeting and enhancing nerve growth, which could address the underlying cause of the condition rather than just alleviating symptoms. This solution is being tested in different dosages, with the aim to identify the most effective concentration for healing, offering hope for faster and more complete recovery for patients.

What evidence suggests that BRM424 Ophthalmic Solution might be an effective treatment for neurotrophic keratitis?

Research shows that BRM424 Eye Drops could help treat neurotrophic keratitis (NK), a serious eye condition. Earlier studies found that treatments like BRM424 can quickly heal damaged corneas. In this trial, participants will receive either Dose1 or Dose2 of BRM424 Ophthalmic Solution. Similar research has shown that patients experienced significant improvements, suggesting that BRM424 might effectively heal the severe corneal damage seen in NK, offering new hope for those facing this difficult condition. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Stage 2 or Stage 3 Neurotrophic Keratitis, a condition affecting the cornea of the eye. Participants must be able to give informed consent. It's not specified who can't join, but typically those with conditions that could interfere with the study are excluded.

Inclusion Criteria

My eye condition is at stage 2 or 3.

Provide written informed consent

Exclusion Criteria

I do not have any active eye infections or inflammation unrelated to NK.

I am a woman who can have children and am not using birth control.

I will need to wear contact lenses for eye correction during the treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BRM424 Ophthalmic Solution to assess initial efficacy and safety in patients with Stage 2 and Stage 3 Neurotrophic Keratitis

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BRM424 Ophthalmic Solution

Trial Overview The trial is testing two different doses of BRM424 Ophthalmic Solution to see how effective they are in treating Neurotrophic Keratitis and to check their safety and tolerability in patients.

How Is the Trial Designed?

Group I: BRM424 Ophthalmic Solution - Dose1 Active Control 1 Intervention

Group II: BRM424 Ophthalmic Solution - Dose2 Active Control 1 Intervention

Who Is Running the Clinical Trial?

BRIM Biotechnology Inc.

Lead Sponsor

Trials

4

Recruited

1,100+

Published Research Related to This Trial

In a study of 23 pediatric patients with refractory uveitis, biological response modifiers (BRM) showed promising results, with infliximab leading to a 77% improvement in visual acuity and a 77% reduction in inflammation.

BRM treatments were found to be safe for children and can serve as effective adjunctive therapies for managing difficult cases of childhood uveitis, with varying efficacy observed among different BRM agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biological response modifier therapy for refractory childhood uveitis. Gallagher, M., Quinones, K., Cervantes-Castañeda, RA., et al.[2022]

Brimonidine tartrate ophthalmic solution 0.15% significantly improved low-contrast visual acuity and contrast sensitivity in patients experiencing night-vision difficulties after laser refractive surgery, with effects observed as soon as one hour after administration.

After one month of treatment, all six patients reported subjective improvements in their night vision, indicating that brimonidine tartrate can provide lasting benefits for up to a month post-treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of brimonidine tartrate 0.15% on night-vision difficulty and contrast testing after refractive surgery. Edwards, JD., Burka, JM., Bower, KS., et al.[2015]

Topical application of brimonidine tartrate 0.1% for one week resulted in significant concentrations of the drug in the vitreous (mean 4.8 nM) and aqueous humor (mean 336.0 nM) of patients undergoing eye surgery, indicating effective penetration of the medication.

The presence of brimonidine in the vitreous was observed in 79% of patients, and the concentration was sufficient to activate neuroprotective receptors, suggesting potential therapeutic benefits for retinal protection, regardless of whether the patients had natural or artificial lenses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitreous and aqueous concentrations of brimonidine following topical application of brimonidine tartrate 0.1% ophthalmic solution in humans. Takamura, Y., Tomomatsu, T., Matsumura, T., et al.[2015]

Brimonidine tartrate (BRT) proniosomes were developed to enhance the stability and bioavailability of the drug for glaucoma treatment, achieving an entrapment efficiency of 79.23% and significantly improved drug release over 24 hours.

In vivo studies demonstrated that the proniosome formulation provided 5.024 times greater ocular bioavailability and 7.90 times longer mean residence time compared to the standard treatment, Alphagan®P, while also showing no ocular irritation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proniosomal gel-derived niosomes: an approach to sustain and improve the ocular delivery of brimonidine tartrate; formulation, in-vitro characterization, and in-vivo pharmacodynamic study. Emad Eldeeb, A., Salah, S., Ghorab, M.[2023]

In a pilot study involving 20 eyes, topical brimonidine 0.2% applied before laser treatment for choroidal neovascularization significantly improved visual outcomes compared to a placebo, with a P-value of 0.027.

The results suggest that brimonidine may protect the neuroretina from damage during laser treatment, highlighting its potential as a neuroprotective agent in eye care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical brimonidine reduces collateral damage caused by laser photocoagulation for choroidal neovascularization. Ferencz, JR., Gilady, G., Harel, O., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05927428

Assessment of the Initial Efficacy and Safety of BRM424 ... The objective of this study is to obtain initial efficacy of BRM424 in patients with Stage 2 and Stage 3 NK and evaluate safety and tolerability. Official Title.

2. trialx.com trialx.com/clinical-trials/listings/301383/assessment-of-the-initial-efficacy-and-safety-of-brm424-ophthalmic-solutions-in-patients-with-neurotrophic-keratitis/

Assessment of the Initial Efficacy and Safety of BRM424 ... Overview. The objective of this study is to obtain initial efficacy of BRM424 in patients with Stage 2 and Stage 3 NK and evaluate safety ...

3. withpower.com withpower.com/trial/phase-2-keratitis-8-2023-338f7

BRM424 Ophthalmic Solution for Neurotrophic Keratitis In a study of 23 pediatric patients with refractory uveitis, biological response modifiers (BRM) showed promising results, with infliximab leading to a 77% ...

4. ophthalmologytimes.com ophthalmologytimes.com/view/brim-submits-ind-for-brim424-phase-2-study-treating-neurotrophic-keratitis

BRIM submits IND for BRIM424 phase 2 study treating ... “Therefore, it can rapidly repair the damaged cornea, and potentially be used to treat patients with severe corneal damage.”

5. synapse.patsnap.com synapse.patsnap.com/drug/a584e362770f42bb9ac520418ab0190d

BRM-424 - Drug Targets, Indications, Patents An Open-Label, Multi-Center, Phase 2 Dose Ranging Study of BRM424 Ophthalmic Solution in Patients With Neurotrophic Keratitis (NK). 100 Clinical Results ...

6. ophthalmologytimes.com ophthalmologytimes.com/view/brim-biotechnology-receives-fda-orphan-drug-designation-for-treatment-of-neurotrophic-keratitis

BRIM Biotechnology receives FDA orphan drug ... Using the NK rabbit model, BRM424 has demonstrated preclinical efficacy and safety in compliance with regulatory requirements. Newsletter. Don't ...

7. glance.eyesoneyecare.com glance.eyesoneyecare.com/press-releases/brim-biotechnology-receives-fda-odd-for-brm424-to-treat-neurotrophic-keratitis/

BRIM Biotechnology receives FDA ODD for BRM424 to ... BRIM Biotechnology receives FDA ODD for BRM424 to treat neurotrophic keratitis. ... eye disease, which is about to begin phase 3 clinical trials.