CSB-001 Eye Drops for Neurotrophic Keratitis

Recruiting at 47 trial locations

Overseen By Clinical Operations Representative

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Claris Biotherapeutics, Inc.

Must not be taking: Oxervate, Topical treatments

Disqualifiers: Active ocular infection, Herpetic keratitis, others

Compensation: Varies

Number of Visits: Unknown

131 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests CSB-001, a new treatment for people with moderate to severe neurotrophic keratitis. The treatment aims to help heal the damaged surface of their eyes. Cenegermin, a nerve growth factor eye drop, has shown promise in improving corneal sensitivity and healing in neurotrophic keratitis.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop all current medications, but you can continue oral antibiotics if you're already taking them. You may also use preservative-free antibiotic eye drops and certain glaucoma eye drops during the study.

What data supports the effectiveness of the drug CSB-001 Eye Drops for Neurotrophic Keratitis?

Research shows that hepatocyte growth factor (HGF), a component of CSB-001, has protective and neuroprotective effects in various eye conditions, such as retinal degeneration and injury, which suggests it might help in treating neurotrophic keratitis. ^{1 2 3 4 5}

Is CSB-001 Eye Drops safe for use in humans?

The safety of CSB-001 Eye Drops, which contains a form of hepatocyte growth factor (HGF), has not been directly addressed in the provided research articles. However, HGF has been studied for its protective effects in eye conditions, suggesting it may have a role in eye health. More specific safety data for CSB-001 in humans would be needed to confirm its safety profile. ^{3 4 5 6 7}

How is the drug CSB-001 Eye Drops unique for treating neurotrophic keratitis?

CSB-001 Eye Drops use a human recombinant form of hepatocyte growth factor (HGF), which is unique because HGF has neuroprotective effects and promotes cell growth and healing, potentially offering a novel approach for treating neurotrophic keratitis compared to other growth factor-based treatments. ^{1 5 8 9 10}

Eligibility Criteria

This trial is for people with moderate to severe neurotrophic keratitis, which affects the cornea of the eye. Participants must have shown no improvement despite standard treatments and be willing to follow study procedures. They can't join if they've used Oxervate recently, have other eye diseases needing treatment during the study (except controlled glaucoma), or any active infections in their eyes.

Inclusion Criteria

I have stage 2 or 3 neurotrophic keratitis.

Pinhole distance visual acuity score ≤ 75 ETDRS letters measured with a LogMAR chart (≥ 0.2 LogMAR, ≤ 20/32 Snellen or worse Snellen or ≤ 0.625 decimal fraction) in the study eye

Subjects must have the ability and willingness to comply with study procedures

Exclusion Criteria

I have an eye condition other than glaucoma that needs treatment.

I used Oxervate for my eye condition within the last 2 months.

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

Controlled Treatment

Participants receive randomized treatment or vehicle control four times daily for 8 weeks

8 weeks

Weekly visits from Day 0 to Week 8, and at Week 10

Open-label Uncontrolled Treatment

Participants in the vehicle arm who are not healed may opt into an open-label treatment phase

Not specified

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

Treatment Details

Interventions

• CSB-001 Ophthalmic Solution 0.1%
• Vehicle Control

Trial Overview The trial tests CSB-001 Ophthalmic Solution against a placebo control. Participants are randomly chosen to receive either the test medication or placebo, applying it four times daily for 8 weeks with weekly clinic visits. Those on placebo without healing may later try the actual drug in an open-label phase.

Participant Groups

Group I: CSB-001 Investigational Treatment Arm Experimental Treatment 1 Intervention

One drop CSB-001 four times daily for 8 weeks in the study eye

Group II: Vehicle Control Arm Placebo Group 1 Intervention

One drop matching vehicle four times daily for 8 weeks in the study eye

Who Is Running the Clinical Trial?

Claris Biotherapeutics, Inc.

Lead Sponsor

Trials

3

Recruited

220+

Findings from Research

Patients with retinitis pigmentosa (RP) have significantly higher levels of hepatocyte growth factor (HGF) in their aqueous humor compared to control subjects, with concentrations of 958.75 pg/mL versus 403.52 pg/mL, respectively.

This elevated HGF level in RP patients suggests a potential role for HGF as a neuroprotective treatment, highlighting its importance in future therapeutic strategies for managing RP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aqueous humor levels of hepatocyte growth factor in retinitis pigmentosa. Salom, D., Diaz-Llopis, M., Quijada, A., et al.[2010]

In a study involving 24 New Zealand rabbits undergoing Epi-LASIK, higher levels of hepatocyte growth factor (HGF) in tears were associated with increased corneal haze, indicating a potential biomarker for post-surgical healing.

Rabbits with a deeper ablation of 150 µm exhibited more significant corneal haze and elevated HGF levels compared to those with a 100 µm ablation, suggesting that the depth of corneal ablation influences both healing response and haze formation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Association between hepatocyte growth factor in tears and corneal haze in rabbits early after epipolis laser in situ keratomileusis]. Chen, J., Han, SN., Zou, XL., et al.[2020]

In a study involving Sprague-Dawley rats, intravitreal injection of hepatocyte growth factor (HGF) significantly protected against degeneration of photoreceptors and retinal pigment epithelium (RPE) after sodium iodate treatment, as evidenced by improved scotopic b-wave thresholds and amplitudes.

HGF-treated eyes showed better preservation of outer retinal structure and larger azide response amplitudes compared to untreated eyes, suggesting its potential as a therapeutic agent for retinal degeneration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protective effect of hepatocyte growth factor against degeneration of the retinal pigment epithelium and photoreceptor in sodium iodate-injected rats. Ohtaka, K., Machida, S., Ohzeki, T., et al.[2013]

Hepatocyte growth factor (HGF) levels are significantly elevated in the vitreous fluid of patients with proliferative diabetic retinopathy (PDR) compared to nondiabetic control patients, indicating a potential role in the disease's progression.

Both HGF and vascular endothelial growth factor (VEGF) concentrations are higher in patients with active PDR than in those with quiescent PDR, suggesting that HGF may contribute to neovascularization associated with the active stage of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatocyte growth factor in vitreous fluid of patients with proliferative diabetic retinopathy and other retinal disorders. Katsura, Y., Okano, T., Noritake, M., et al.[2019]

In a rat model of retinal ischemia-reperfusion injury, hepatocyte growth factor (HGF) was found to be upregulated, indicating its potential role in the injury response.

Administering recombinant human HGF intravitreally significantly improved retinal function and reduced cell death, demonstrating its neuroprotective effects against retinal damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expression and neuroprotective effect of hepatocyte growth factor in retinal ischemia-reperfusion injury. Shibuki, H., Katai, N., Kuroiwa, S., et al.[2009]

References

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

Aqueous humor levels of hepatocyte growth factor in retinitis pigmentosa. [2010]

2. China pubmed.ncbi.nlm.nih.gov

[Association between hepatocyte growth factor in tears and corneal haze in rabbits early after epipolis laser in situ keratomileusis]. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Protective effect of hepatocyte growth factor against degeneration of the retinal pigment epithelium and photoreceptor in sodium iodate-injected rats. [2013]

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

Hepatocyte growth factor in vitreous fluid of patients with proliferative diabetic retinopathy and other retinal disorders. [2019]

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

Expression and neuroprotective effect of hepatocyte growth factor in retinal ischemia-reperfusion injury. [2009]

6. Spain pubmed.ncbi.nlm.nih.gov

Cenegermin for the treatment of dry eye disease. [2023]

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

The regulatory role of hepatoma-derived growth factor as an angiogenic factor in the eye. [2018]

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

Functional CNTF receptor alpha subunit restored by its recombinant in corneal endothelial cells in stored human donor corneas: connexin-43 upregulation. [2016]

9. China pubmed.ncbi.nlm.nih.gov

Progress on the application of growth factor-related drugs in ophthalmology. [2023]

10. England pubmed.ncbi.nlm.nih.gov

A New Treatment for Recalcitrant Neurotrophic Keratopathy of Ocular Graft-Versus-Host Disease with Virus Infection. [2023]