KPI-012 for Corneal Ulcers

(CHASE Trial)

Recruiting at 33 trial locations

Overseen By Kala Clinical Development

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Combangio, Inc

Must not be taking: Oxervate, Doxycycline, Chemotherapy, others

Disqualifiers: Ocular infection, Corneal burns, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing KPI-012, a stem cell-based eye drop, on patients with a chronic eye condition called PCED. The treatment aims to help heal the eye surface using substances secreted by stem cells.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use certain treatments like Oxervate in the study eye within 30 days, systemic doxycycline, or chemotherapeutic agents within 7 days before the study.

What data supports the effectiveness of the treatment KPI-012 for corneal ulcers?

Research shows that components of KPI-012, like mesenchymal stem cell secretome (MSC-S), help heal corneal wounds by promoting cell growth and reducing inflammation. Studies found that MSC-S, especially its exosomes (tiny particles that carry signals between cells), improved corneal healing and reduced cloudiness in the eye. ^{1 2 3 4 5}

Is KPI-012 safe for use in humans?

Research on mesenchymal stem cell secretome (MSC-S), which is part of KPI-012, shows it has been used safely in studies for corneal wound healing. It has anti-inflammatory and healing properties, and no significant safety issues have been reported in the studies reviewed. ^{1 2 5 6 7}

How is the treatment KPI-012 different from other treatments for corneal ulcers?

KPI-012 is unique because it uses a solution derived from human mesenchymal stem cells (MSCs) to promote healing and reduce inflammation in corneal ulcers. This approach leverages the natural healing properties of MSCs, which is different from traditional treatments that may not directly use stem cell components. ^{5 8 9 10 11}

Research Team

Kristie Veasey

Principal Investigator

Kala Pharmaceuticals, Inc.

Eligibility Criteria

This trial is for individuals with PCED, a type of corneal ulcer, lasting at least 7 days due to conditions like diabetes-related eye disease or infections. Participants should not have had recent eye surgery, be using certain medications, or have severe eyelid issues. Pregnant or breastfeeding individuals are excluded.

Inclusion Criteria

PCED measurements meet study criteria.

I have had persistent corneal epithelial defects for over a week due to an eye condition.

Exclusion Criteria

I will be taking doxycycline.

I haven't had eye surgery in the last 90 days.

Use of another investigational agent within 30 days

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Safety Evaluation

Initial cohort of at least 2 participants to evaluate the safety of the high strength product

2 weeks

Treatment

Participants receive KPI-012 or vehicle for 8 weeks

8 weeks

Daily administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

Treatment Details

Interventions

• KPI-012 Ophthalmic Solution (Other)

Trial Overview The study aims to test the safety and effectiveness of KPI-012 ophthalmic solution compared to a placebo (vehicle) in treating PCED. It's designed to see if KPI-012 can help heal the cornea better than a non-active solution.

Participant Groups

Group I: Cohort 2, Arm 2 Experimental Treatment 1 Intervention

KPI-012 High Dose KPI-012 Ophthalmic Solution 3 U/mL 1 drop 4 times/day for 56 days

Group II: Cohort 2, Arm 1 Experimental Treatment 1 Intervention

KPI-012 Low Dose KPI-012 Ophthalmic Solution 1 U/mL 1 drop 4 times/day for 56 days

Group III: Cohort 1, Arm 1 Experimental Treatment 1 Intervention

KPI-012 High Dose KPI-012 Ophthalmic Solution 3 U/mL 1 drop 4 times/day for 56 days

Group IV: Cohort 2, Arm 3 Placebo Group 1 Intervention

KPI-012 Vehicle KPI-012 Ophthalmic Solution 0 U/mL 1 drop 4 times/day for 56 days

Who Is Running the Clinical Trial?

Combangio, Inc

Lead Sponsor

Trials

1

Recruited

90+

Kala Pharmaceuticals, Inc.

Industry Sponsor

Trials

11

Recruited

4,200+

Findings from Research

The study found that the secretome from human bone-marrow-derived mesenchymal stromal/stem cells (MSC-S) significantly promotes corneal wound healing, with extracellular vesicles (EVs) being the key active components responsible for this effect.

MSC-S showed optimal efficacy in a dose-dependent manner, with higher concentrations and longer incubation periods enhancing healing, while the secretome remained stable for up to 4 weeks under standard storage conditions, indicating its potential for clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Wound-Healing Effects of Mesenchymal Stromal Cell Secretome in the Cornea and the Role of Exosomes. An, S., Anwar, K., Ashraf, M., et al.[2023]

Subconjunctival injection of human mesenchymal stromal cells (hMSCs) significantly reduced corneal inflammation and squamous metaplasia in mice with graft versus host disease (GVHD), indicating its therapeutic efficacy.

The treatment effectively prevented immune cell infiltration (CD3+ cells) in the cornea and normalized tear osmolarity, suggesting that hMSCs can help restore corneal health in ocular GVHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subconjunctival injection of mesenchymal stromal cells protects the cornea in an experimental model of GVHD. Martínez-Carrasco, R., Sánchez-Abarca, LI., Nieto-Gómez, C., et al.[2020]

Both intrastromal and subconjunctival injections of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) effectively healed corneal epithelial injuries in a study involving 24 mice, but the intrastromal method was found to be significantly more effective.

The intrastromal injection not only reduced the area of epithelial defects more than the subconjunctival injection but also led to better outcomes in terms of corneal opacity and neovascularization, indicating it may be the preferred method for treating corneal injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intrastromal versus subconjunctival injection of mesenchymal stem/stromal cells for promoting corneal repair. Soleimani, M., Mirshahi, R., Cheraqpour, K., et al.[2023]

Human umbilical cord MSC-derived small extracellular vesicles (HUMSC-sEVs) significantly enhance corneal epithelial cell proliferation and migration, promoting faster wound healing in corneal injuries, as demonstrated in both in vitro and in vivo models.

The healing effects of HUMSC-sEVs are linked to the transfer of miR-21, which reduces PTEN levels and activates the PI3K/Akt signaling pathway, suggesting a specific mechanism of action that could be harnessed for therapeutic purposes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Umbilical Cord Mesenchymal Stem Cell-Derived Small Extracellular Vesicles Deliver miR-21 to Promote Corneal Epithelial Wound Healing through PTEN/PI3K/Akt Pathway. Liu, X., Li, X., Wu, G., et al.[2022]

Human corneal mesenchymal stromal cell (cMSC)-derived exosomes significantly enhance corneal epithelial wound healing, showing a 30.1% remaining wound area in vitro compared to 72.9% in controls after 16 hours.

In vivo studies demonstrated that cMSC exosome treatment resulted in 77.5% wound healing after 72 hours, compared to only 41.6% in the control group, indicating their potential as a therapeutic option for ocular surface injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Human Corneal Mesenchymal Stromal Cell-derived Exosomes on Corneal Epithelial Wound Healing. Samaeekia, R., Rabiee, B., Putra, I., et al.[2022]

Mesenchymal stem cells (MSCs) show promise in treating ocular surface disorders by promoting corneal epithelial repair and influencing various healing pathways through their secretion of trophic factors and cytokines.

Current research is focused on optimizing the dosages and delivery methods of MSCs for conditions like corneal epitheliopathies, but further clinical trials are necessary to establish effective treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Applications of mesenchymal stem cells in ocular surface diseases: sources and routes of delivery. Soleimani, M., Masoumi, A., Momenaei, B., et al.[2023]

Delivering lyophilized mesenchymal stem cell secretome (MSC-S) within a hyaluronic acid and chondroitin sulfate gel significantly enhances corneal wound healing and reduces complications like scarring and neovascularization after injuries, based on a study of corneal injuries.

The combination of MSC-S and the gel increases the expression of CD44 receptors, suggesting that the therapeutic effects are partly due to the activation of these receptors by hyaluronic acid, indicating a novel mechanism of action for improving corneal repair.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Corneal Wound Healing Effects of Mesenchymal Stem Cell Secretome Delivered Within a Viscoelastic Gel Carrier. Fernandes-Cunha, GM., Na, KS., Putra, I., et al.[2022]

Human limbal mesenchymal stromal cells (L-MSCs) exhibit strong immunosuppressive properties, capable of suppressing T-cell proliferation by up to 75%, making them a promising candidate for allogeneic therapies in corneal repair.

Both human and rabbit L-MSCs not only show immunosuppressive qualities but also enhance the growth of limbal epithelial cells, indicating their potential utility in treating corneal disorders and supporting the use of rabbits as a pre-clinical model.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunosuppressive properties of mesenchymal stromal cell cultures derived from the limbus of human and rabbit corneas. Bray, LJ., Heazlewood, CF., Munster, DJ., et al.[2022]

Limbal mesenchymal stem cells (LMSCs) isolated from human corneoscleral rings showed the ability to differentiate into multiple cell types, indicating their potential for regenerative therapies.

These LMSCs maintained important limbal stem cell markers and demonstrated effective growth on amniotic membrane, suggesting they could be useful in corneal repair and transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human limbal mesenchymal stem cells express ABCB5 and can grow on amniotic membrane. Shaharuddin, B., Osei-Bempong, C., Ahmad, S., et al.[2019]

Topical application of bone marrow (BM) cells and CD117-positive hematopoietic stem cells significantly accelerated the healing of alkali-induced corneal ulcers in a study involving 89 eyes of syngenic mice.

The positive effects on corneal wound healing were likely due to soluble factors released by the BM and CD117(+) cells, as these cells were not found integrated into the regenerated corneal epithelium.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bone marrow cells and CD117-positive haematopoietic stem cells promote corneal wound healing. Sel, S., Schilling, UM., Nass, N., et al.[2013]

Corneal endothelial cell substitutes (CECSi) derived from induced pluripotent stem cells (iPSCs) were successfully created using a xeno-free protocol, showing characteristics similar to natural corneal endothelial cells, which is crucial for treating corneal edema.

In a monkey model of corneal edema, transplantation of CECSi cells significantly reduced corneal swelling compared to controls, indicating their potential efficacy in restoring vision for patients with bullous keratopathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transplantation of iPSC-derived corneal endothelial substitutes in a monkey corneal edema model. Hatou, S., Sayano, T., Higa, K., et al.[2021]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Wound-Healing Effects of Mesenchymal Stromal Cell Secretome in the Cornea and the Role of Exosomes. [2023]

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

Subconjunctival injection of mesenchymal stromal cells protects the cornea in an experimental model of GVHD. [2020]

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

Intrastromal versus subconjunctival injection of mesenchymal stem/stromal cells for promoting corneal repair. [2023]

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

Umbilical Cord Mesenchymal Stem Cell-Derived Small Extracellular Vesicles Deliver miR-21 to Promote Corneal Epithelial Wound Healing through PTEN/PI3K/Akt Pathway. [2022]

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

Effect of Human Corneal Mesenchymal Stromal Cell-derived Exosomes on Corneal Epithelial Wound Healing. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Applications of mesenchymal stem cells in ocular surface diseases: sources and routes of delivery. [2023]

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

Corneal Wound Healing Effects of Mesenchymal Stem Cell Secretome Delivered Within a Viscoelastic Gel Carrier. [2022]

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

Immunosuppressive properties of mesenchymal stromal cell cultures derived from the limbus of human and rabbit corneas. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Human limbal mesenchymal stem cells express ABCB5 and can grow on amniotic membrane. [2019]

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

Bone marrow cells and CD117-positive haematopoietic stem cells promote corneal wound healing. [2013]

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

Transplantation of iPSC-derived corneal endothelial substitutes in a monkey corneal edema model. [2021]