E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Limbal stem cell deficiency (LSCD) |
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E.1.1.1 | Medical condition in easily understood language |
Complete or partial loss of vision due to secondary injuries |
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E.1.1.2 | Therapeutic area | Diseases [C] - Eye Diseases [C11] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10072138 |
E.1.2 | Term | Limbal stem cell deficiency |
E.1.2 | System Organ Class | 10015919 - Eye disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 and the safety (by monitoring adverse events [AEs]) of the IMP during and after application. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
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E.4 | Principal 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 tumour 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 a. The surgical procedure (e.g. removing of the conjunctival pannus) b. 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) c. Tear secretion deficiency determined by Schirmer’s test d. Allergy, sensitivity or intolerance to components/excipients of the IMP/ per protocol pre-planned concomitant medications e. Conjunctival scarring with fornix shortening f. General anesthesia (in case general anesthesia is required) or local anesthesia g. 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Primary efficacy endpoint: Response rate at 12 months after IMP application (V16), 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) 2. Primary safety endpoint: - adverse events |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Month 12 after IMP application 2. During all patient visits except screening |
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E.5.2 | Secondary end point(s) |
Secondary efficacy endpoints: 1. response rate at 3 months after IMP application 2. neovascularization measured at V1, V6, V7, V8, V9, V10, V11, V12, V13, V14, V16 3. epithelial defects measured at V1, V7, V9, V11, V13, V14, V16 4. ocular symptoms of pain, photophobia, burning measured at V1, V7, V9, V11, V13, V14, V16 5. ocular inflammation measured at V1, V7, V9, V11, V13, V14, V16 6. corneal opacity measured at V1, V7, V9, V11, V13, V14, V16 7. visual acuity measured at V1, V7, V9, V11, V13, V14, V16 8. quality of life (visual function questionnaire-25 [VFQ-25]) questionnaire (investigator’s version) at V1, V13, V16
Secondary safety endpoint: 9. physical examination performed at V1, V13, V16 10. vital signs measured at V1, V13, V16 11. tonometry measured at V1, V6, V8, V12, V13
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Efficacy: 1. 3 M after IMP application 2. 14 to 9 D before; 1, 2, 3, 4, 5, 6, 7, 12 W, 6, 12 M after IMP application 3. 14 to 9 D before; 2, 4, 6, 12 W, 6, 12 M after IMP application 4. 14 to 9 D before; 2, 4, 6, 12 W, 6, 12 M after IMP application 5. 14 to 9 D before; 2, 4, 6, 12 W, 6, 12 M after IMP application 6. 14 to 9 D before; 2, 4, 12 W, 6, 12 M after IMP application 7. 14 to 9 D before; 2, 4, 6, 12 W, 6, 12 M after IMP application 8. 14 to 9 D before; 12 W, 12 M after IMP application
Safety: 9. 14 to 9 D before IMP application; 12 W, 12 M after IMP application 10. 14 to 9 D before IMP application; 12 W, 12 M after IMP application 11. 14 to 9 D before IMP application; 1, 3, 7, 12 W after IMP application
D: Days W: Weeks M: Months
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Safety and efficacy in patients |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Staggered dosing; Up to four different doses of the IMP |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
No comparator is used in this study; |
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E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |