Allogeneic ABCB5-positive Limbal Stem Cells for Treatment of LSCD

Limbal Stem Cell Deficiency Clinical Trial

Official title:

An Interventional, Open-label, Multicenter Phase I/IIa Clinical Trial to Investigate the Safety and Efficacy of Ascending Doses of Allogeneic ABCB5-positive Limbal Stem Cells (LSC2) for the Treatment of Limbal Stem Cell Deficiency (LSCD)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03549299
• Other study ID #: LSC2-II-01
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: July 4, 2019
• Est. completion date: September 2023

Study information

• Verified date: October 2022
• Source: RHEACELL GmbH & Co. KG
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of this clinical trial is to investigate the efficacy (by monitoring neovascularization and epithelial defects) of up to four doses of the investigational medicinal product (IMP) LSC2 topically administered on the target eye of patients with LSCD. Further, safety of the IMP during and after application will be investigated (by monitoring adverse events [AEs]).

Description:

This is an interventional, open-label, phase I/IIa clinical trial to investigate the efficacy and safety of up to four doses of the IMP topically administered on the target eye of patients with LSCD. Patients will be treated in up to four ascending dose groups. The allogeneic investigational product LSC2 contains ABCB5-positive limbal stem cells (from corneal rims of cadaveric donors, expanded ex vivo, isolated and stored in a donor cell bank). The IMP will be applied on the target eye. Prior to application, the conjunctival pannus will be removed under general or local anesthesia. Patients will be followed up for efficacy for 1 year. Efficacy of the IMP will be monitored by assessing neovascularization and epithelial defects. To assess long-term safety of LSC2 one follow-up visit at Month 24 post IMP application is included.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 16
• Est. completion date: September 2023
• Est. primary completion date: September 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

1. Male or female patients aged 18 to 85 years

2. Patients with secondary bilateral or unilateral LSCD (injury that caused LSCD at least 6 months prior to inclusion)

3. Neovascularization: Vessel penetration of at least 2 quadrants, with central cornea involved

4. Patients understand the nature of the procedure and are providing written informed consent prior to any clinical trial procedure

5. Women of childbearing potential must have a negative blood pregnancy test at Visit 1

6. Women of childbearing potential must be willing to use highly effective contraceptive methods during the course of the clinical trial

Exclusion Criteria:

1. Compromised eyelid mobility and/or symblepharon; patient can be re-screened after appropriate treatment

2. Presence of eyelid malposition; patient can be re-screened after appropriate treatment

3. Active local ocular or systemic infection and/or inflammation. Patient can be re-screened after infection and/or inflammation is resolved.

4. Tumor diseases or history of tumor disease

5. Active ocular neoplastic disease (exclusion will be based on investigator's assessment)

6. Corneal erosion or ulcer is bigger than 4 mm2; corresponding to less than 95% of continuous corneal epithelium. Patient can be re-screened after erosion or ulcer is resolved (= 4 mm2).

7. Positive for human immunodeficiency virus (HIV) 1 and/or 2 (diagnosed by serologic testing)

8. Clinically significant or unstable concurrent disease or other clinical contraindications to stem cell transplantation

9. History of glaucoma

10. Contraindications to trial related procedures/substances including

1. The surgical procedure (e.g. removing of the conjunctival pannus)

2. Contact lens complications due to contact lens use in the proposed trial (based on the Efron Grading scale for standard clinical reference for contact lens complications)

3. Tear secretion deficiency determined by Schirmer's test

4. Allergy, sensitivity or intolerance to components/excipients of the IMP/ per protocol pre-planned concomitant medications

5. Conjunctival scarring with fornix shortening

6. General anesthesia (in case general anesthesia is required) or local anesthesia

7. Immunosuppression (being mandatory concomitant therapy)

11. Intraocular pressure (IOP) of =30 mm Hg

12. History or clinical signs of stroke or transient ischemic attacks

13. Active or suspected ocular or periocular infections

14. Active or suspected intraocular inflammation

15. Further clinical contraindications to IMP application (exclusion will be based upon investigator's judgment)

16. Current or previous (within 30 days of enrollment) treatment with another IMP, or participation and/or under follow-up in another clinical trial

17. Previous participation in this clinical trial (except screening failure due to inclusion criterion 2 and/or exclusion criterion 1 and/or 2 and/or 3 and/or 6)

18. Known abuse of alcohol, drugs, or medicinal products

19. Patients unwilling or unable to comply with the requirements of the protocol

20. Lactating women

21. Evidence of any other medical conditions (such as psychiatric illness, physical examination, or laboratory findings) that may interfere with the planned treatment, affect the patient's compliance, or place the patient at high risk of complications related to the treatment

22. Employees of the sponsor, or employees or relatives of the investigator

Related Conditions & MeSH terms

• Limbal Stem Cell Deficiency

Intervention

Biological:
• LSC2
Topical application of IMP on target eye

Locations

Country	Name	City	State
Germany	Universitäts-Klinikum Heidelberg, Kopfklinik	Heidelberg
Germany	Universitäts-Klinikum Jena, Augenklinik	Jena
Germany	Universitäts-Klinikum Köln, Augenklinik	Köln
Germany	Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Augenklinik und Poliklinik	Mainz
United States	Massachusetts Eye and Ear Infirmary	Boston	Massachusetts

Sponsors (4)

Lead Sponsor	Collaborator
RHEACELL GmbH & Co. KG	FGK Clinical Research GmbH, Granzer Regulatory Consulting & Services, Ticeba GmbH

Countries where clinical trial is conducted

United States,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response rate at 12 months after IMP application	Response rate at 12 months after IMP application, where response is defined as: no or mild corneal neovascularization (no vessel penetration or vessel penetration up to 1 quadrant, without central cornea) AND; no or mild epithelial defects (no corneal erosion or ulcer are present (corneal wounds are closed) or minimal superficial staining)	Month 12
Primary	Assessment of adverse event (AE) occurrence	All AEs occurring during the clinical trial will be registered, documented and evaluated.	Up to 24 months.
Secondary	Response rate at 3 months after IMP application	Response rate at 3 months after IMP application, where response is defined as: no or mild corneal neovascularization (no vessel penetration or vessel penetration up to 1 quadrant, without central cornea) AND; no or mild epithelial defects (no corneal erosion or ulcer are present (corneal wounds are closed) or minimal superficial staining)	Month 3
Secondary	Neovascularization	Corneal neovascularization will be assessed as "none" (no blood vessel penetration), "mild" (blood vessel penetration of 1 quadrant, without central cornea involvement), "moderate" (blood vessel penetration of 1 quadrant, with central cornea involvement or blood vessel penetration of 2 or 3 quadrants, with or without central cornea involvement) or "strong" (blood vessel penetration of all quadrants, with or without central cornea involvement).	Baseline, week 1, 2, 3, 4, 5, 6, 7, 12, month 6 and 12
Secondary	Epithelial defects	Epithelial defects will be assessed as "none" (no corneal erosion or ulcer are present (corneal wounds are closed)) or "mild" (minimal superficial staining) or "moderate" (dense coalescent staining up to 2 mm in diameter) or "strong" (dense coalescent staining greater than 2 mm in diameter) by means of fluorescein staining.	Baseline, week 2, 4, 6, month 3, 6 and 12
Secondary	Ocular symptoms of pain, photophobia, burning	Photophobia and burning will be assessed as "no complaint" (grade 0), "mild" (grade 1), "moderate" (grade 2) or "severe" (grade 3).; Pain assessment will be done by the patient using a 11-point numerical rating scale ranging between no pain (zero) and worst imaginable pain (ten).	Baseline, week 2, 4, 6, 12, month 6 and 12
Secondary	Ocular inflammation	The assessment of inflammation will be categorized as present (yes) or nonexistent (no).	Baseline, week 2, 4, 6, 12, month 6 and 12
Secondary	Corneal opacity	Corneal opacification will be assessed as "none" (no corneal opacification), "mild" (corneal opacification in up to 1 quadrant, without central cornea involvement), "moderate" (corneal opacification in 1 quadrant, with central cornea involvement or corneal opacification in 2 or 3 quadrants, with or without central cornea involvement) or "strong" (corneal opacification in all quadrants, with or without central cornea involvement).; Additional densitometric Pentacam® measurements are optional. Opacity values of the following ring-shaped corneal segments will be record: 0 - 2 mm, 2 - 6 mm, 6 - 10 mm, 10 - 12 mm (anterior, central and posterior corneal layer for each segment); 0 - 2 mm, 2 - 6 mm, 6 - 10 mm, 10 - 12 mm (full thickness average for each segment); Anterior layer of the complete cornea (0 - 12 mm); Central layer of the complete cornea (0 - 12 mm); Posterior of the complete cornea (0 - 12 mm); Overall cornea (0 - 12 mm, full thickness)	Baseline, week 2, 4, 6, 12, month 6 and 12
Secondary	Visual acuity	Clarity of vision.	Baseline, week 2, 4, 6, 12, month 6 and 12
Secondary	Quality of life assessment	Quality of life (visual function questionnaire-25 [VFQ-25]) questionnaire to be answered.	Baseline, week 12, month 12
Secondary	Physical examination	A full physical examination will be performed at week 12 and abnormal physical examination results will be evaluated and reported as AEs.	Baseline, week 12, month 12
Secondary	Tonometry		Baseline,week 1, 3, 7 and 12
Secondary	Vital signs: Body temperature at Baseline, week 12, month 12	Body temperature at Baseline, week 12 and month 12 will be evaluated.	Baseline, week 12, month 12
Secondary	Vital signs: Blood pressure at Baseline, week 12, month 12	Blood pressure at Baseline, week 12 and month 12 will be evaluated.	Baseline, week 12, month 12
Secondary	Vital signs: Heart rate at Baseline, week 12, month 12	Heart rate at Baseline, week 12 and month 12 will be evaluated.	Baseline, week 12, month 12