Allogeneic adipose-derived adult mesenchymal stem cells expanded for Dry eye disease | Graft-versus-host disease

Inclusion criteria

• {"criterion_text":"- Patients over 18 years of age who understand and sign the informed consent.\n- Diagnosis of severe cGVHD according to NIH criteria (reviewed by Lee SJ. in 2017) with ocular involvement in the form of severe dry eye disease in both eyes of more than 3 months' duration and objectively defined as superficial punctate keratitis >2 on the Oxford scale (range, 0-5) and/or presence of epithelial defect and, in addition, subjectively as a serious symptomatology, > 33 points in the OSDI questionnaire (0-100).\n- Patients must have been previously treated, for at least three months, with blood derivatives and/or insulin eye drops and topical cyclosporine or tacrolimus (unless any of them has not been tolerated and has had to be discontinued for this reason);\n- Patients should be using ocular lubricants at least 4 times a day and still have the criteria for severe dry eye disease in point 2.\n- Patients in treatment with low doses of maintenance topical corticosteroids should have been on a stable dose for at least one month prior to inclusion\n- The doses and frequency of application of all topical medicines with which the patient initiates the trial should be able to remain unchanged for the duration of the trial, unless otherwise judged by the investigator at a particular time.\n- Systemic treatment of chronic GVHD should be stable in terms of the use of systemic immunosuppressants at least in the last month before patient inclusion or before treatment application.\n- Negative urine pregnancy test result at baseline for women of childbearing potential. Subjects should be instructed to use contraception during their participation in the clinical trial and to take a new pregnancy test at the treatment visit if more than 28 days have passed since the baseline visit."}

Exclusion criteria

• {"criterion_text":"- Uncontrolled systemic disease or any disease that, in medical judgment, could put the patient at risk or the interpretation of the results.\n- Uncontrolled systemic cGvHD\n- Active eye infection.\n- Eye surgery within the last 3 months.\n- Initiation of topical therapies for dry eye disease indicated in the inclusion criteria after 3 months prior to inclusion.\n- Initiation of topical corticosteroid use during the 4 weeks prior to inclusion.\n- Cognitive alterations that may interfere with the fulfillment of the study.\n- Pregnant or breastfeeding women."}

Primary endpoints

• {"endpoint_text":"- Significant improvement in ocular surface integrity as measured by fluorescein corneal staining. A clinically significant improvement is defined as an improvement in superficial punctate keratitis (SPK) of at least one unit compared to baseline, according to the Oxford scale (range 0-5) and, if there is an epithelial defect, a decrease of at least 3/4 of its initial size.","definition_or_measurement_approach":"Measured by fluorescein corneal staining; clinically significant improvement = ≥1 unit improvement in SPK on Oxford scale (0-5) or, if epithelial defect present, decrease of at least 3/4 of initial size."}
• {"endpoint_text":"- Significant increase in tear production values evaluated with the Schirmer test under topical anesthesia by at least 2 mm.","definition_or_measurement_approach":"Measured by Schirmer test with topical anesthesia; significant increase defined as ≥2 mm increase."}
• {"endpoint_text":"- Significant decrease in the degree of conjunctival hyperemia by at least one point (Efron scale, 0-4).","definition_or_measurement_approach":"Assessed by Efron scale (0-4); significant decrease = at least 1 point."}
• {"endpoint_text":"- Significant improvement, in at least one point, of the parameters related to the Meibomian glands (Efron scale, 0-4).","definition_or_measurement_approach":"Measured by Efron scale (0-4) for Meibomian gland parameters; improvement = ≥1 point."}
• {"endpoint_text":"- Significant improvement of any of the findings in the central cornea, assessed by in vivo confocal microscopy: (a) improvement of at least one grade (3 grades: corneal, mixed, conjunctival) in epithelial phenotype. b) significant decrease in the density of dendritic cells in the corneal stroma; c) improvement in the characteristics of the sub-basal corneal nerve plexus (number of nerves, density, length, tortuosity and nerve branching).","definition_or_measurement_approach":"Assessed by in vivo confocal microscopy; endpoints include (a) ≥1 grade improvement in epithelial phenotype, (b) decrease in dendritic cell density in corneal stroma, (c) improvements in sub-basal nerve plexus metrics (number, density, length, tortuosity, branching)."}
• {"endpoint_text":"- Clinical improvement of symptoms, evaluated with clinical questionnaires (OSDI, mSIDEQ, NRS, WFPRS and CDES-Q). Clinical improvement with at least one of the questionnaires will be considered sufficient.","definition_or_measurement_approach":"Patient-reported outcome questionnaires (OSDI, mSIDEQ, NRS, WFPRS, CDES-Q); improvement on at least one questionnaire considered sufficient."}

Secondary endpoints

• {"endpoint_text":"- Rate of adverse events related to the application of subconjunctival injection of ASC.","definition_or_measurement_approach":"Frequency/rate of adverse events attributed to subconjunctival ASC injection."}
• {"endpoint_text":"- Analysis of ocular marker expression in the administered ASCs. To analyze the effect of freezing ASCs in relation to these markers and to establish, if possible, a correlation between the expression of these markers in the applied cells and clinical outcomes.","definition_or_measurement_approach":"Laboratory analysis of marker expression in administered ASCs; comparison of fresh vs frozen cells and correlation with clinical outcomes."}
• {"endpoint_text":"- Analysis of the presence and concentration of 48 inflammation-related molecules in tear and serum samples and see their effect on the clinical improvement of patients.","definition_or_measurement_approach":"Quantification of 48 inflammation-related molecules in tear and serum samples and analysis of association with clinical improvement."}
• {"endpoint_text":"- Search for new biomarkers that can be used to objectively assess the evolution of patients affected by cRHD and with ocular involvement.","definition_or_measurement_approach":"Exploratory biomarker discovery analyses on clinical samples to identify objective markers of disease evolution."}
• {"endpoint_text":"- Percentage of clinical improvement of the lower dose (6.25 millions of ASCs) compared to the higher dose (12.5 millions of ASCs).","definition_or_measurement_approach":"Comparative analysis of clinical improvement rates between 6.25 million ASC dose and 12.5 million ASC dose."}

Spain

Earliest CTIS Part Ii Submission Date

14-03-2025

Latest Decision Or Authorization Date

20-11-2025

Processing Time Days

251

Number Of Sites

2

Number Of Participants

30

Primary sponsor

Full Name

Fundacion De Investigacion Biomedica De Salamanca

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

Spain