ACCE Transplant for Limbal Stem Cell Deficiency

(CECA Trial)

Recruiting at 3 trial locations

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: CHU de Quebec-Universite Laval

Disqualifiers: Pregnancy, Breast-feeding, Allergy, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Immediate post-surgery

54 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment Autologous Cultured Corneal Epithelium (CECA) for Limbal Stem Cell Deficiency?

Research shows that using cultured autologous corneal epithelium (CACE) for treating limbal stem cell deficiency (LSCD) is promising, with 87% of patients achieving clearer corneas and improved vision. This suggests that CECA, a similar treatment, could also be effective for LSCD. ^{1 2 3 4 5}

Is the ACCE Transplant for Limbal Stem Cell Deficiency safe for humans?

Research shows that using cultured autologous corneal epithelium (CACE) for treating limbal stem cell deficiency is generally safe, with no major adverse events reported in studies involving patients. Other similar treatments, like cultivated autologous limbal epithelial cells (CALEC), also showed no primary safety issues in early trials. ^{1 2 3 6 7}

How is the ACCE Transplant treatment for Limbal Stem Cell Deficiency different from other treatments?

The ACCE Transplant treatment uses Autologous Cultured Corneal Epithelium (CECA), which involves grafting stem cell-containing cultured corneal epithelium to avoid the risk of damaging the donor eye, unlike other treatments that may cause limbal stem cell deficiency in the donor eye. This approach is unique because it uses a small biopsy from the patient's own eye to create a graft that can restore the corneal surface and improve vision. ^{1 2 3 8 9}

What is the purpose of this trial?

The study " Autologous cultured corneal epithelium (CECA) for the treatment of corneal lesions associated with limbal stem cell deficiency" is the first clinical trial of this product manufactured at the LOEX laboratory. The culture of corneal epithelium strives to produce a reconstructed tissue with the therapeutical aim of treatment of limbal stem cell deficiency. The study is a phase I/phase II study with the goal to evaluate safety and efficacy of the CECA graft for the treatment of human patients suffering from limbal stem cell deficiency. The trial is open to all genders. The inclusion of 5 minors is planned.

Research Team

Ralph Kyrillos, MD FRCS (C)

Principal Investigator

CHU de Quebec

Eligibility Criteria

This trial is for individuals with Limbal Stem Cell Deficiency (LSCD) in one or both eyes. Participants can be adults of any gender, including minors, but must have a small area of healthy limbus tissue for biopsy. Those who are pregnant, breastfeeding, unable to consent, or allergic to certain medications like Trasylol(R) cannot join.

Inclusion Criteria

I am under 18 years old.

I have limbal stem cell deficiency in one or both eyes but enough healthy tissue for a safe biopsy.

My gender does not affect my eligibility.

Exclusion Criteria

The donor eye is not healthy enough for a safe small biopsy.

You are currently breastfeeding a child.

known allergy to aprotinine (Trasylol (R))

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Surgical transplantation of Autologous Cultured Corneal Epithelium (ACCE) graft for the treatment of corneal lesions

Immediate post-surgery

Follow-up

Participants are monitored for safety and effectiveness after treatment, including anatomic assessment, visual acuity, pain level, and quality of life measurements

1 year

Treatment Details

Interventions

• Autologous Cultured Corneal Epithelium (CECA)

Trial Overview The study tests the safety and effectiveness of transplanting Autologous Cultured Corneal Epithelium (CECA), grown in a lab from the patient's own cells, as a treatment for LSCD. This Phase I/II trial aims to repair corneal lesions by replacing damaged tissue.

Participant Groups

Group I: ACCE (Autologous Cultured Corneal Epithlium) graft for the treatment of corneal lesions Experimental Treatment 1 Intervention

Surgical transplantation of Autologous Cultured Corneal Epithelium

Autologous Cultured Corneal Epithelium (CECA) is already approved in Japan for the following indications:

Approved in Japan as Nepic for:

• Limbal stem cell deficiency

Who Is Running the Clinical Trial?

CHU de Quebec-Universite Laval

Lead Sponsor

Trials

177

Recruited

110,000+

Findings from Research

Transplantation of autologous conjunctival epithelial cells cultivated ex vivo (EVCAU) in 12 eyes of 10 patients with total limbal stem cell deficiency (LSCD) showed an 83.3% improvement in clinical parameters over an average follow-up of 18.5 months.

The cultivated cells formed multiple layers and exhibited positive markers for healthy corneal epithelium, indicating that EVCAU transplantation can effectively reconstruct the corneal surface in LSCD patients, although further long-term studies are needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transplantation of conjunctival epithelial cells cultivated ex vivo in patients with total limbal stem cell deficiency. Ricardo, JR., Cristovam, PC., Filho, PA., et al.[2022]

The study involved 15 patients who received cultured autologous corneal epithelium (CACE) grafts, demonstrating a low occurrence of major adverse events, indicating the safety of this treatment for limbal stem cell deficiency (LSCD).

After one year, 53% of patients showed functional success in improving their best corrected visual acuity (BCVA), and by the last follow-up, 87% achieved corneal clarity, suggesting promising efficacy of CACE in restoring corneal surface structures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cultured Autologous Corneal Epithelia for the Treatment of Unilateral Limbal Stem Cell Deficiency: A Case Series of 15 Patients. Guérin, LP., Larouche, D., Morcos, MW., et al.[2022]

In a study of nine patients with limbal stem cell deficiency (LSCD), 55.6% experienced improvements in symptoms or corneal health after receiving autologous limbal epithelial cell transplants expanded in a completely animal product-free medium.

The use of autologous serum as the sole growth supplement in the culture system minimizes risks associated with animal-derived products, such as disease transmission and immune reactions, making this approach safer for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical transplantation of ex vivo expanded autologous limbal epithelial cells using a culture medium with human serum as single supplement: a retrospective case series. Pathak, M., Cholidis, S., Haug, K., et al.[2013]

Transplanting autologous conjunctival epithelium is an effective method for treating bilateral corneal limbal stem cell deficiency, showing positive outcomes without complications like symblepharon or severe keratinization.

A new feeder-free and serum-free culture system for limbal epithelium was developed, which can also be used for culturing conjunctival epithelia, enhancing the practicality of this treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ocular Surface Reconstruction with the Autologous Conjunctival Epithelium and Establishment of a Feeder-Free and Serum-Free Culture System. Yamagami, S., Yokoo, S., Sakimoto, T.[2018]

Limbal stem cell deficiency (LSCD) can lead to serious complications like corneal vascularization and vision loss, often resulting from extensive damage due to injury or disease.

Various transplantation techniques, including whole limbal grafts and ex vivo-expanded limbal cells, can effectively restore the limbus and treat LSCD, highlighting the importance of tailored treatment approaches based on the severity and cause of the deficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Corneal Epithelial Stem Cells-Physiology, Pathophysiology and Therapeutic Options. Ruan, Y., Jiang, S., Musayeva, A., et al.[2021]

The study developed a new method for creating cultivated autologous limbal epithelial cells (CALEC) for treating unilateral limbal stem cell deficiency, using a safe, serum-free, and antibiotic-free process, which maintained the cells' stemness and viability.

In a phase 1 clinical trial with five patients, four received CALEC transplants with no primary safety events reported, indicating preliminary feasibility and paving the way for further trials to assess long-term safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cultivated autologous limbal epithelial cell (CALEC) transplantation: Development of manufacturing process and clinical evaluation of feasibility and safety. Jurkunas, UV., Yin, J., Johns, LK., et al.[2023]

A novel technique using FDA-approved contact lenses to transfer autologous stem cells has shown promising results in restoring a healthy corneal epithelium in three patients with limbal stem cell deficiency (LSCD), with follow-up periods of 8-13 months.

All patients experienced significant improvements, including increased best-corrected visual acuity and no recurrence of complications like conjunctivalization or corneal vascularization, indicating both safety and efficacy of this method.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A contact lens-based technique for expansion and transplantation of autologous epithelial progenitors for ocular surface reconstruction. Di Girolamo, N., Bosch, M., Zamora, K., et al.[2022]

In a study of 30 patients who underwent autologous simple limbal epithelial transplantation (SLET) after failed cultivated limbal epithelial transplantation (CLET), 80% of the eyes maintained a successful outcome over a mean follow-up of 2.3 years, indicating SLET's effectiveness in treating recurrent limbal stem cell deficiency (LSCD).

SLET showed a significantly higher success rate (80%) compared to repeat CLET (53.5%), and it also resulted in notable improvements in visual acuity and other ocular health indicators, making it a preferable and cost-effective option for patients with LSCD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simple limbal epithelial transplantation (SLET) in failed cultivated limbal epithelial transplantation (CLET) for unilateral chronic ocular burns. Basu, S., Mohan, S., Bhalekar, S., et al.[2019]

This study successfully generated multilayered oral mucosa epithelium (OME) using a completely animal product-free method, which reduces the risk of pathogen transmission and graft rejection.

Transplantation of the autologous OME in two patients with bilateral limbal stem cell deficiency resulted in successful restoration of ocular surface function for up to 24 months, demonstrating the efficacy of this innovative approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful application of ex vivo expanded human autologous oral mucosal epithelium for the treatment of total bilateral limbal stem cell deficiency. Kolli, S., Ahmad, S., Mudhar, HS., et al.[2022]

References

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

Transplantation of conjunctival epithelial cells cultivated ex vivo in patients with total limbal stem cell deficiency. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Cultured Autologous Corneal Epithelia for the Treatment of Unilateral Limbal Stem Cell Deficiency: A Case Series of 15 Patients. [2022]

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

Clinical transplantation of ex vivo expanded autologous limbal epithelial cells using a culture medium with human serum as single supplement: a retrospective case series. [2013]

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

Ocular Surface Reconstruction with the Autologous Conjunctival Epithelium and Establishment of a Feeder-Free and Serum-Free Culture System. [2018]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Corneal Epithelial Stem Cells-Physiology, Pathophysiology and Therapeutic Options. [2021]

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

Cultivated autologous limbal epithelial cell (CALEC) transplantation: Development of manufacturing process and clinical evaluation of feasibility and safety. [2023]

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

A contact lens-based technique for expansion and transplantation of autologous epithelial progenitors for ocular surface reconstruction. [2022]

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

Simple limbal epithelial transplantation (SLET) in failed cultivated limbal epithelial transplantation (CLET) for unilateral chronic ocular burns. [2019]

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

Successful application of ex vivo expanded human autologous oral mucosal epithelium for the treatment of total bilateral limbal stem cell deficiency. [2022]