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)
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Limbal Stem Cell Deficiency
- Sponsor
- RHEACELL GmbH & Co. KG
- Enrollment
- 16
- Locations
- 5
- Primary Endpoint
- Assessment of adverse event (AE) occurrence
- Status
- Active, Not Recruiting
- Last Updated
- 3 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female patients aged 18 to 85 years
- •Patients with secondary bilateral or unilateral LSCD (injury that caused LSCD at least 6 months prior to inclusion)
- •Neovascularization: Vessel penetration of at least 2 quadrants, with central cornea involved
- •Patients understand the nature of the procedure and are providing written informed consent prior to any clinical trial procedure
- •Women of childbearing potential must have a negative blood pregnancy test at Visit 1
- •Women of childbearing potential must be willing to use highly effective contraceptive methods during the course of the clinical trial
Exclusion Criteria
- •Compromised eyelid mobility and/or symblepharon; patient can be re-screened after appropriate treatment
- •Presence of eyelid malposition; patient can be re-screened after appropriate treatment
- •Active local ocular or systemic infection and/or inflammation. Patient can be re-screened after infection and/or inflammation is resolved.
- •Tumor diseases or history of tumor disease
- •Active ocular neoplastic disease (exclusion will be based on investigator's assessment)
- •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).
- •Positive for human immunodeficiency virus (HIV) 1 and/or 2 (diagnosed by serologic testing)
- •Clinically significant or unstable concurrent disease or other clinical contraindications to stem cell transplantation
- •History of glaucoma
- •Contraindications to trial related procedures/substances including
Outcomes
Primary Outcomes
Assessment of adverse event (AE) occurrence
Time Frame: Up to 24 months.
All AEs occurring during the clinical trial will be registered, documented and evaluated.
Response rate at 12 months after IMP application
Time Frame: Month 12
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)
Secondary Outcomes
- Quality of life assessment(Baseline, week 12, month 12)
- Vital signs: Blood pressure at Baseline, week 12, month 12(Baseline, week 12, month 12)
- Vital signs: Heart rate at Baseline, week 12, month 12(Baseline, week 12, month 12)
- Neovascularization(Baseline, week 1, 2, 3, 4, 5, 6, 7, 12, month 6 and 12)
- Epithelial defects(Baseline, week 2, 4, 6, month 3, 6 and 12)
- Ocular symptoms of pain, photophobia, burning(Baseline, week 2, 4, 6, 12, month 6 and 12)
- Response rate at 3 months after IMP application(Month 3)
- Ocular inflammation(Baseline, week 2, 4, 6, 12, month 6 and 12)
- Vital signs: Body temperature at Baseline, week 12, month 12(Baseline, week 12, month 12)
- Physical examination(Baseline, week 12, month 12)
- Corneal opacity(Baseline, week 2, 4, 6, 12, month 6 and 12)
- Visual acuity(Baseline, week 2, 4, 6, 12, month 6 and 12)
- Tonometry(Baseline,week 1, 3, 7 and 12)