KPI-012 for Corneal Ulcers

(CHASE Trial)

No longer recruiting at 41 trial locations

Overseen By Kala Clinical Development

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Combangio, Inc

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

Disqualifiers: Ocular infection, Corneal burns, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new eye drop treatment called KPI-012 for individuals with persistent corneal epithelial defects (PCED), a condition where the eye's surface fails to heal properly due to severe dry eye or post-surgery complications. The trial aims to determine the safety and effectiveness of KPI-012 compared to a placebo. Participants will receive either a low dose, high dose, or placebo for 56 days. This trial may suit those who have experienced PCED for at least a week due to conditions like diabetic eye issues or previous eye surgery. As a Phase 2 trial, the 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 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.

Is there any evidence suggesting that KPI-012 Ophthalmic Solution is likely to be safe for humans?

Research has shown that KPI-012, an eye drop treatment, is safe. It is well-tolerated, with no harmful reactions reported. In one study, participants using a similar treatment experienced no major side effects. This suggests KPI-012 might be safe for those considering joining the trial. The treatment aims to help heal corneal ulcers, which are open sores on the eye. Overall, KPI-012 appears to have a good safety record, making it a promising option for people with this eye condition. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for corneal ulcers?

Researchers are excited about KPI-012 for corneal ulcers because it offers a new approach with a unique mechanism of action. Unlike traditional treatments that primarily focus on reducing inflammation or infection, KPI-012 uses a novel ophthalmic solution that may promote healing by targeting the underlying cellular processes. It comes in two different doses, allowing flexibility in treatment and the potential for optimizing effectiveness. This innovative method could lead to better healing outcomes and faster recovery times for patients with corneal ulcers.

What evidence suggests that KPI-012 might be an effective treatment for corneal ulcers?

Research has shown that KPI-012, a treatment derived from mesenchymal stem cells, holds promise for healing corneal ulcers. In an earlier study, 75% of participants experienced complete healing of their eye lesions during the treatment. Another study found that the treatment helped all corneal ulcers heal within four weeks, with most healing in just over a week. KPI-012 promotes healing and reduces swelling in the eye. This trial will evaluate different dosages of KPI-012, including low and high doses, alongside a placebo comparator. KPI-012 presents a hopeful option for individuals with persistent corneal epithelial defects (PCED). ^{2 5 6 7 8}

Who Is on the Research Team?

Kristie Veasey

Principal Investigator

Kala Pharmaceuticals, Inc.

Are You a Good Fit for This Trial?

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.

Use of another investigational agent within 30 days

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• KPI-012 Ophthalmic Solution

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

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sciencedirect.com

sciencedirect.com/science/article/pii/S0011393X25000244

Safety and Efficacy of a Mesenchymal Stem Cell ...

In the efficacy cohort (n = 9), 6 of 8 participants (75%) demonstrated complete healing of the lesion during the treatment period, with 4 of 8 (50%) achieving ...

2.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40538945/

Safety and Efficacy of a Mesenchymal Stem Cell ...

KPI-012 is a topical mesenchymal stem cell secretome therapy under investigation for PCED management. Objective: To assess the safety, ...

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clinicaltrials.gov

clinicaltrials.gov/study/NCT05727878

Trial to Evaluate Safety and Efficacy of KPI-012 Ophthalmic ...

The primary objective of the study is to investigate the safety and efficacy of KPI-012 compared to vehicle in participants who have a documented clinical ...

4.

sciencedirect.com

sciencedirect.com/science/article/pii/S0034528825000335

The therapeutic potential of mesenchymal stromal cell ...

Our results showed that secretome therapy facilitated complete healing of all corneal ulcers within 4 weeks, with an average healing time of 1.2 weeks. Notably, ...

5.

withpower.com

withpower.com/trial/phase-2-persistent-corneal-epithelial-defects-1-2023-9d199

KPI-012 for Corneal Ulcers (CHASE Trial)

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 ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12177151/

Safety and Efficacy of a Mesenchymal Stem Cell Secretome ...

Twice daily KPI-012 therapy exhibits a favorable safety profile-efficacy profile and may promote rapid wound healing.

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subspecialtyday.ascrs.org

subspecialtyday.ascrs.org/-/media/all-annual-meetings/am-2022/am-22-files/poster-winners/86697.pdf

Safety and Efficacy of a Novel Mesenchymal Stem Cell ...

➢ KPI-012 is an ophthalmic solution of human bone marrow- derived mesenchymal stem cell (MSC) secretome which contains numerous biofactors ...

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investors.kalarx.com

investors.kalarx.com/news-releases/news-release-details/kala-pharmaceuticals-announces-positive-safety-update-cohort-1

release details - Investors - KALA BIO, Inc.

KPI-012 is currently in clinical development for the treatment of persistent corneal epithelial defect (PCED), a rare disease of impaired ...