CSB-001 Ophthalmic Solution for Limbal Stem Cell Deficiency

Recruiting at 5 trial locations

Overseen By Central Operations Representative

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Claris Biotherapeutics, Inc.

Must be taking: Acthar

Disqualifiers: Active ocular infection, Recent ocular surgery, others

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

Compensation: Varies

Number of Visits: Unknown

65 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new eye drop treatment called CSB-001 for individuals with limbal stem cell deficiency (LSCD), a condition affecting the cornea that can lead to vision problems. Participants will receive the eye drops in one or both eyes during two separate 8-week periods, followed by observation. The trial seeks individuals whose corneas are affected in the central area and have been diagnosed with LSCD, even after stable treatment. The researchers aim to determine if CSB-001 can improve eye health and manage LSCD symptoms. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are taking Acthar, you must have been on a stable dose for about 8 weeks and plan to continue the same dose during the trial.

Is there any evidence suggesting that CSB-001 Ophthalmic Solution is likely to be safe for humans?

Research shows that CSB-001, an eye drop solution being tested for limbal stem cell deficiency (LSCD), remains in the early stages of testing. The main goal at this point is to assess its safety for humans. Since CSB-001 is among the first to be studied in people, limited information exists about its safety.

However, because CSB-001 is in an early phase trial, researchers closely monitor it for any side effects. Early trials like this carefully check for potential problems, ensuring participants receive close monitoring to catch any issues.

If CSB-001 proves safe, it could advance to later testing stages where researchers will evaluate its effectiveness. Currently, safety is the primary focus, and the study will gather that crucial information. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard treatments for limbal stem cell deficiency, which often involve surgical procedures like limbal stem cell transplants or amniotic membrane transplantation, CSB-001 Ophthalmic Solution is an eye drop that offers a non-invasive approach. Researchers are excited about CSB-001 because it targets the eyes directly with a simple, topical application, potentially making it more accessible and less risky than surgical options. Additionally, this solution is designed to be used over a controlled, extended period, which may help in regenerating and maintaining the health of limbal stem cells more effectively. This new delivery method could provide a significant advantage in terms of patient comfort and ease of use.

What evidence suggests that CSB-001 Ophthalmic Solution might be an effective treatment for limbal stem cell deficiency?

Research shows that CSB-001, an eye drop, is being developed to treat limbal stem cell deficiency (LSCD). This condition affects the eye's surface, causing healing issues and vision problems. CSB-001 contains a modified form of a natural substance that may help repair and regenerate damaged eye cells. Early results suggest it could improve healing of the eye's surface and restore some protective functions. In this trial, participants will either receive CSB-001 four times daily or be observed without intervention initially, followed by CSB-001 treatment. Although initial findings are promising, more research is needed to confirm its effectiveness in people. ^{2 3 4 5 6}

Are You a Good Fit for This Trial?

This trial is for individuals with limbal stem cell deficiency (LSCD), a condition affecting the eyes. Participants will receive CSB-001 Ophthalmic Solution in one or both eyes if they qualify. Specific eligibility criteria are not provided, but typically include having LSCD without other major eye diseases and being able to follow the study protocol.

Inclusion Criteria

I have eye inflammation not caused by an infection that won't affect my trial participation.

Sponsor written confirmation of qualifying LSCD diagnosis

I've been on a stable Acthar dose for 8 weeks with little improvement in my condition.

Exclusion Criteria

Presence or history of any ocular or systemic disorder, condition, or procedure that might hinder the efficacy of the study treatment or its evaluation, or could interfere with the interpretation of study results, in the opinion of the investigator

I do not have any active eye infections.

I had eye surgery less than 30 days ago and my healing is not complete.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dosing Phase I

Participants receive CSB-001 ophthalmic solution four times daily for 8 weeks

8 weeks

Dosing Holiday

A period where no test article is administered

31-40 days

Dosing Phase II

Participants receive CSB-001 ophthalmic solution four times daily for another 8 weeks

8 weeks

Observation Phase

Participants are observed in a non-interventional phase

28 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• CSB-001 Ophthalmic Solution 0.1%

Trial Overview The safety and effectiveness of CSB-001 Ophthalmic Solution at 0.1% concentration are being tested on people with LSCD. The study has two main dosing phases separated by a break, followed by an observation phase to monitor long-term effects.

How Is the Trial Designed?

Group I: Control Experimental Treatment 1 Intervention

Observation (non-interventional) for 20 weeks followed by one drop CSB-001 four times daily for two 8-week dosing periods in the study eye(s) separated by \>30 days and \<40 days followed by observation (non-interventional) for 52 weeks (total participation of 96 weeks)

Group II: CSB-001 QID Experimental Treatment 1 Intervention

One drop CSB-001 four times daily for two 8-week dosing periods in the study eye(s) separated by \>30 days and \<40 days followed by observation (non-interventional) for 72 weeks (total participation of 96 weeks)

Who Is Running the Clinical Trial?

Claris Biotherapeutics, Inc.

Lead Sponsor

Trials

3

Recruited

220+

Published Research Related to This Trial

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]

Freezing human retinal pigment epithelial (RPE) cells increases the level of hepatocyte growth factor (HGF) and promotes the proliferation of these cells, suggesting a potential method for enhancing RPE cell growth.

Tedelparin, a low molecular weight heparin, reduces HGF levels and suppresses the proliferation of RPE cells, indicating that it may inhibit the beneficial effects of freezing on RPE cell growth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The effect of freezing and low molecular weight heparin treatment on the production of hepatocyte growth factor of human RPE cells]. Wang, F., Song, ZY., Tao, XF., et al.[2018]

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]

A new method using fluorescence-activated cell sorting (FACS) allows for the efficient isolation of pure populations of human limbal melanocytes (LM) by targeting the CD117 (c-Kit) cell surface marker.

The isolated limbal melanocytes maintain their ability to self-renew and produce melanin, making them valuable for research in stem cell-based corneal tissue engineering.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isolation and enrichment of melanocytes from human corneal limbus using CD117 (c-Kit) as selection marker. Polisetti, N., Schlötzer-Schrehardt, U., Reinhard, T., et al.[2021]

In a study of 13 eyes from 12 patients with limbal stem cell deficiency (LSCD) following glaucoma surgery, autologous serum eye drops (AS) were found to be well tolerated with no serious adverse effects reported.

While AS treatment did not significantly improve the LSCD severity or best-corrected visual acuity over time, it stabilized the condition in 69.2% of cases, suggesting potential benefits in managing LSCD progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous Serum Eye Drops in the Management of Limbal Stem Cell Deficiency Associated With Glaucoma Surgery. Niruthisard, D., Bonnet, C., Tanasugarn, L., et al.[2023]

Hepatocyte growth factor (HGF) protects retinal pigment epithelial (RPE) cells from oxidative injury caused by glutathione depletion, as evidenced by reduced apoptosis and increased levels of mitochondrial glutathione after HGF treatment.

HGF appears to enhance the expression of antioxidant genes and counteracts the activation of caspase-3 induced by oxidative stress, suggesting a mechanism where HGF helps maintain cellular health during oxidative challenges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatocyte growth factor protects RPE cells from apoptosis induced by glutathione depletion. Jin, M., Yaung, J., Kannan, R., et al.[2013]

A new protocol was developed to efficiently isolate pure populations of limbal mesenchymal stromal cells (LMSC), limbal melanocytes (LM), and limbal epithelial progenitor cells (LEPC) from human corneal limbus tissue, enabling better study of their roles in the limbal stem cell niche.

Co-culturing LMSC and LM with LEPC led to the formation of a stratified epithelium and helped maintain the LEPC phenotype, suggesting that these niche cells play a crucial role in supporting the health and function of corneal epithelial cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficient Isolation and Functional Characterization of Niche Cells from Human Corneal Limbus. Polisetti, N., Sharaf, L., Schlötzer-Schrehardt, U., et al.[2022]

ABCB5 is identified as a crucial marker for limbal stem cells (LSCs), which are essential for maintaining corneal health and regeneration; its presence is linked to successful corneal repair and development.

Transplanting ABCB5-positive LSCs can fully restore corneal function in LSC-deficient mice, highlighting the potential for targeted therapies in treating corneal blindness caused by LSC deficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ABCB5 is a limbal stem cell gene required for corneal development and repair. Ksander, BR., Kolovou, PE., Wilson, BJ., et al.[2022]

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]

Cotransplantation of limbal stem cells (LSCs) and limbal stromal stem cells (LSSCs) significantly improved corneal healing in a rabbit model of limbal stem cell deficiency (LSCD), with graft survival rates of 87.5% compared to 37.5% for LSCs alone.

LSSCs not only supported the repair process by differentiating into keratocytes but also produced factors that enhanced epithelial growth and reduced inflammation, indicating their crucial role in corneal regeneration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cotransplantation of Limbal Epithelial and Stromal Cells for Ocular Surface Reconstruction. Zhu, L., Zhang, W., Zhu, J., et al.[2022]

In a first-in-human trial involving 39 refractory cancer patients, the monoclonal antibody YYB101 demonstrated a favorable safety profile, with no dose-limiting toxicities observed and manageable side effects such as generalized edema and fatigue.

YYB101 showed preliminary efficacy, with 2.5% of patients achieving a partial response and 43.5% maintaining stable disease, leading to plans for further studies combining YYB101 with irinotecan for metastatic colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-human phase I trial of anti-hepatocyte growth factor antibody (YYB101) in refractory solid tumor patients. Kim, ST., Hong, JY., Park, SH., et al.[2022]

Hepatocyte growth factor (HGF) promotes the proliferation of human embryonic stem cell-derived retinal pigment epithelial (hESC-RPE) cells, indicating its potential role in enhancing cell therapy for retinal diseases.

Blocking HGF signaling with a receptor inhibitor negatively impacts the proliferation of hESC-RPE cells and disrupts eye development in chicken embryos, suggesting that HGF is crucial for RPE development and could be beneficial in increasing hESC-RPE cell numbers for future therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatocyte growth factor promotes the proliferation of human embryonic stem cell derived retinal pigment epithelial cells. Karamali, F., Esfahani, MN., Hajian, M., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06452316?spons=Claris%20Biotherapeutics,%20Inc&rank=1

Study to Evaluate the Safety and Efficacy of CSB-001 ... Study to Evaluate the Safety and Efficacy of CSB-001 Ophthalmic Solution 0.1% in Subjects With Limbal Stem Cell Deficiency. ClinicalTrials.gov ID NCT06452316.

2. pharmaceutical-technology.com pharmaceutical-technology.com/data-insights/csb-001-claris-biotherapeutics-limbal-stem-cell-deficiency-lscd-likelihood-of-approval/

CSB-001 by Claris Biotherapeutics for Limbal Stem Cell ... CSB-001 is a under development for the treatment of stage 2 and 3 neurotrophic keratitis, limbal stem cell deficiency and corneal scars.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12097425/

Limbal stem cell deficiency approaches and limbal niche ... CSB-001 (NCT06452316), Phase I, Topical ophthalmic solution 0.1% human recombinant dHGF (5-amino acid deleted hepatocyte growth factor). MSC, Phase II ...

4. globaldata.com globaldata.com/store/report/csb-001-in-limbal-stem-cell-deficiency-lscd-loa-innovation-and-trend-analysis/

CSB-001 in Limbal Stem Cell Deficiency (LSCD ... - GlobalData CSB-001 is a under development for the treatment of stage 2 and 3 neurotrophic keratitis, limbal stem cell deficiency and corneal scars. It is ...

5. synapse.patsnap.com synapse.patsnap.com/drug/99eaa71699a144d6815e5fbe3854032c

CSB-001 - Drug Targets, Indications, Patents This leads to impaired corneal healing through a loss of protective mechanisms such as blinking. The cornea becomes vulnerable to persistent epithelial defects, ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06452316

Study to Evaluate the Safety and Efficacy of CSB-001 ... Study to Evaluate the Safety and Efficacy of CSB-001 Ophthalmic Solution 0.1% in Subjects With Limbal Stem Cell Deficiency. ClinicalTrials.gov ID NCT06452316.