Clinical trial NCT03549299: Allogeneic ABCB5-positive Limbal Stem Cells for Treatment of LSCD
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)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Limbal Stem Cell Deficiency
Keywords: limbal stem cell deficiency
ABCB5
Limbal stem cells
LSCs
LSC
allogeneic
tissue engineered product
phase I/IIa
Lead sponsor: RHEACELL GmbH & Co. KG
Sponsor class: INDUSTRY
Collaborators: name: FGK Clinical Research GmbH
name: Ticeba GmbH
name: Granzer Regulatory Consulting & Services
First posted: 2018-06-08
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients will be treated in up to four ascending dose groups. After the first treated patient of the first dose group (Group A) was followed for 2 weeks, a safety and tolerability assessment of the applied IMP dose will be conducted by an internal committee. The same approach applies to the second subject.

Dose escalation and recruitment of additional patients into the second dose group (Group B) will depend on the safety and tolerability of the IMP in Group A. A safety and tolerability assessment will be conducted after the last treated patient of the first dose group (Group A) was followed for 12 weeks.

The same approach applies to Group C and D.
Primary purpose: TREATMENT

Brief 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 \[AEs\]).

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Response rate at 12 months after IMP application
timeFrame: Month 12
measure: Assessment of adverse event (AE) occurrence
timeFrame: Up to 24 months.
Secondary outcomes:
measure: Response rate at 3 months after IMP application
timeFrame: Month 3
measure: Neovascularization
timeFrame: Baseline, week 1, 2, 3, 4, 5, 6, 7, 12, month 6 and 12
measure: Epithelial defects
timeFrame: Baseline, week 2, 4, 6, month 3, 6 and 12
measure: Ocular symptoms of pain, photophobia, burning
timeFrame: Baseline, week 2, 4, 6, 12, month 6 and 12
measure: Ocular inflammation
timeFrame: Baseline, week 2, 4, 6, 12, month 6 and 12
measure: Corneal opacity
timeFrame: Baseline, week 2, 4, 6, 12, month 6 and 12
measure: Visual acuity
timeFrame: Baseline, week 2, 4, 6, 12, month 6 and 12
measure: Quality of life assessment
timeFrame: Baseline, week 12, month 12
measure: Physical examination
timeFrame: Baseline, week 12, month 12
measure: Tonometry
timeFrame: Baseline,week 1, 3, 7 and 12
measure: Vital signs: Body temperature at Baseline, week 12, month 12
timeFrame: Baseline, week 12, month 12
measure: Vital signs: Blood pressure at Baseline, week 12, month 12
timeFrame: Baseline, week 12, month 12
measure: Vital signs: Heart rate at Baseline, week 12, month 12
timeFrame: Baseline, week 12, month 12
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts Eye and Ear Infirmary
state: Massachusetts
city: Heidelberg
country: Germany
facility: Universitäts-Klinikum Heidelberg, Kopfklinik
city: Jena
country: Germany
facility: Universitäts-Klinikum Jena, Augenklinik
city: Köln
country: Germany
facility: Universitäts-Klinikum Köln, Augenklinik
city: Mainz
country: Germany
facility: Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Augenklinik und Poliklinik
Study officials:
affiliation: Universitäts-Klinikum Heidelberg, Kopfklinik, Heidelberg, Germany
name: Gerd U. Auffarth, Prof.Dr.med.
role: PRINCIPAL_INVESTIGATOR
References: