CSB-001 Ophthalmic Solution for Limbal Stem Cell Deficiency

Recruiting in Palo Alto (17 mi)

+5 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Claris Biotherapeutics, Inc.

Must be taking: Acthar

Disqualifiers: Active ocular infection, Recent ocular surgery, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This study will enroll subjects with qualifying limbal stem cell deficiency (LSCD). All subjects will receive CSB-001 investigational drug in either one or both study eyes. The study is comprised of two identical phases (Dosing Phase I and II) of test article dosing separated by a 31- to 40-day period, the Dosing Holiday, where no test article is administered. Dosing Phase II is followed by an observational, noninterventional phase (Observation Phase).

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.

What data supports the effectiveness of the drug CSB-001 Ophthalmic Solution 0.1% for Limbal Stem Cell Deficiency?

Research shows that hepatocyte growth factor (HGF), a component of the drug, can promote the growth of certain eye cells, which suggests it might help in conditions like Limbal Stem Cell Deficiency by encouraging cell repair and growth. ^{1 2 3 4 5}

Is CSB-001 Ophthalmic Solution safe for humans?

There is no specific safety data available for CSB-001 Ophthalmic Solution, but a related treatment using an anti-hepatocyte growth factor antibody (YYB101) has shown safety in early human trials for other conditions. ^{1 2 5 6 7}

How does the drug CSB-001 Ophthalmic Solution differ from other treatments for limbal stem cell deficiency?

CSB-001 Ophthalmic Solution is unique because it uses a human recombinant form of hepatocyte growth factor, which may promote healing and regeneration of the corneal surface by stimulating cell growth and repair, unlike traditional treatments that often rely on transplantation of stem cells. ^{8 9 10 11 12}

Research Team

Eligibility Criteria

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

Sponsor written confirmation of qualifying LSCD diagnosis

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

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.

Trial Timeline

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

Treatment Details

Interventions

• CSB-001 Ophthalmic Solution 0.1% (Stem Cell Therapy)

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.

Participant Groups

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 for 8 weeks (total participation of 48 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 28 weeks (total participation of 48 weeks)

Who Is Running the Clinical Trial?

Claris Biotherapeutics, Inc.

Lead Sponsor

Trials

3

Recruited

220+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

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

Hepatocyte growth factor promotes the proliferation of human embryonic stem cell derived retinal pigment epithelial cells. [2020]

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

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

3. China 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]. [2018]

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

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

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

Hepatocyte growth factor protects RPE cells from apoptosis induced by glutathione depletion. [2013]

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

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

7. England pubmed.ncbi.nlm.nih.gov

First-in-human phase I trial of anti-hepatocyte growth factor antibody (YYB101) in refractory solid tumor patients. [2022]

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

Isolation and enrichment of melanocytes from human corneal limbus using CD117 (c-Kit) as selection marker. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Efficient Isolation and Functional Characterization of Niche Cells from Human Corneal Limbus. [2022]

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

Autologous Serum Eye Drops in the Management of Limbal Stem Cell Deficiency Associated With Glaucoma Surgery. [2023]

11. England pubmed.ncbi.nlm.nih.gov

ABCB5 is a limbal stem cell gene required for corneal development and repair. [2022]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Cotransplantation of Limbal Epithelial and Stromal Cells for Ocular Surface Reconstruction. [2022]