Allogeneic ABCB5-positive Limbal Stem Cells for Treatment of LSCD
- Conditions
- Limbal Stem Cell Deficiency
- Interventions
- Biological: LSC2
- Registration Number
- NCT03549299
- Lead Sponsor
- RHEACELL GmbH & Co. KG
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 16
- 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
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Compromised eyelid mobility and/or symblepharon; patient can be re-screened after appropriate treatment
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Presence of eyelid malposition; patient can be re-screened after appropriate treatment
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Active local ocular or systemic infection and/or inflammation. Patient can be re-screened after infection and/or inflammation is resolved.
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Tumor diseases or history of tumor disease
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Active ocular neoplastic disease (exclusion will be based on investigator's assessment)
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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).
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Positive for human immunodeficiency virus (HIV) 1 and/or 2 (diagnosed by serologic testing)
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Clinically significant or unstable concurrent disease or other clinical contraindications to stem cell transplantation
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History of glaucoma
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Contraindications to trial related procedures/substances including
- The surgical procedure (e.g. removing of the conjunctival pannus)
- 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)
- Tear secretion deficiency determined by Schirmer's test
- Allergy, sensitivity or intolerance to components/excipients of the IMP/ per protocol pre-planned concomitant medications
- Conjunctival scarring with fornix shortening
- General anesthesia (in case general anesthesia is required) or local anesthesia
- Immunosuppression (being mandatory concomitant therapy)
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Intraocular pressure (IOP) of ≥30 mm Hg
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History or clinical signs of stroke or transient ischemic attacks
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Active or suspected ocular or periocular infections
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Active or suspected intraocular inflammation
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Further clinical contraindications to IMP application (exclusion will be based upon investigator's judgment)
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Current or previous (within 30 days of enrollment) treatment with another IMP, or participation and/or under follow-up in another clinical trial
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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)
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Known abuse of alcohol, drugs, or medicinal products
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Patients unwilling or unable to comply with the requirements of the protocol
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Lactating women
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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
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Employees of the sponsor, or employees or relatives of the investigator
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description LSC2; 7.5 x 10^4 cells LSC2 Single dose of LSC2, 7.5 x 10\^4 cells per patient LSC2; 3.0 x 10^5 cells LSC2 Single dose of LSC2, 3.0 x 10\^5 cells per patient LSC2; 8.0 x 10^5 cells LSC2 Single dose of LSC2, 8.0 x 10\^5 cells per patient LSC2; 1.2 x 10^6 cells LSC2 Single dose of LSC2, 1.2 x 10\^6 cells per patient
- Primary Outcome Measures
Name Time Method Assessment of adverse event (AE) occurrence 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 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 Outcome Measures
Name Time Method Quality of life assessment Baseline, week 12, month 12 Quality of life (visual function questionnaire-25 \[VFQ-25\]) questionnaire to be answered.
Vital signs: Blood pressure at Baseline, week 12, month 12 Baseline, week 12, month 12 Blood pressure at Baseline, week 12 and month 12 will be evaluated.
Vital signs: Heart rate at Baseline, week 12, month 12 Baseline, week 12, month 12 Heart rate at Baseline, week 12 and month 12 will be evaluated.
Neovascularization Baseline, week 1, 2, 3, 4, 5, 6, 7, 12, month 6 and 12 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).
Epithelial defects Baseline, week 2, 4, 6, month 3, 6 and 12 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.
Ocular symptoms of pain, photophobia, burning Baseline, week 2, 4, 6, 12, month 6 and 12 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).Response rate at 3 months after IMP application Month 3 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)Ocular inflammation Baseline, week 2, 4, 6, 12, month 6 and 12 The assessment of inflammation will be categorized as present (yes) or nonexistent (no).
Vital signs: Body temperature at Baseline, week 12, month 12 Baseline, week 12, month 12 Body temperature at Baseline, week 12 and month 12 will be evaluated.
Physical examination Baseline, week 12, month 12 A full physical examination will be performed at week 12 and abnormal physical examination results will be evaluated and reported as AEs.
Corneal opacity Baseline, week 2, 4, 6, 12, month 6 and 12 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)Visual acuity Baseline, week 2, 4, 6, 12, month 6 and 12 Clarity of vision.
Tonometry Baseline,week 1, 3, 7 and 12
Trial Locations
- Locations (5)
Massachusetts Eye and Ear Infirmary
🇺🇸Boston, Massachusetts, United States
Universitäts-Klinikum Köln, Augenklinik
🇩🇪Köln, Germany
Universitäts-Klinikum Jena, Augenklinik
🇩🇪Jena, Germany
Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Augenklinik und Poliklinik
🇩🇪Mainz, Germany
Universitäts-Klinikum Heidelberg, Kopfklinik
🇩🇪Heidelberg, Germany