Clinical Trial to evaluate the efficacy and safety of cell therapy for dry eye disease in Graft-versus-Host Disease (GvHD) context.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacion De Investigacion Biomedica De Salamanca

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11]

Decision date (initial)

2025-07-16

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Instituto de Salud Carlos III (ISCIII)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To assess the efficacy and safety of subconjunctival ASC injection in patients with cGVHD and ocular involvement (severe Dry eye disease), by assessing the clinically and statistically significant improvement in disease-specific signs and symptoms.

Secondary objectives 5

1. To analyse and study adverse events related to the application of subconjunctival ASC injection in patients with cGVHD and ocular involvement (severe DES) to confirm the safety of subconjunctival administration of ASC in patients affected by ocular cGVHD.
2. To establish new biomarkers that can be used to objectively assess the evolution of patients affected by cGVHD and with ocular involvement (severe ADD).
3. To study the relationship of the expression of markers on the ocular surface by ASCs with their clinical efficacy, as well as the variation in the expression of these markers in relation to cell preservation methods
4. To assess the quality of life of patients treated with the two doses of MSC using the NEI VFQ-25 questionnaire (25-item National Eye Institute Visual Function Questionnaire).
5. To assess impact of cell dose on clinical improvement.

Conditions and MedDRA coding

Dry eye disease in patients with Graft versus Host disease patients

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Patients over 18 years of age who understand and sign the informed consent.
2. 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).
3. 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);
4. 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.
5. 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
6. 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.
7. 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.
8. 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 8

1. Uncontrolled systemic disease or any disease that, in medical judgment, could put the patient at risk or the interpretation of the results.
2. Uncontrolled systemic cGvHD
3. Active eye infection.
4. Eye surgery within the last 3 months.
5. Initiation of topical therapies for dry eye disease indicated in the inclusion criteria after 3 months prior to inclusion.
6. Initiation of topical corticosteroid use during the 4 weeks prior to inclusion.
7. Cognitive alterations that may interfere with the fulfillment of the study.
8. Pregnant or breastfeeding women.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 6

1. 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.
2. Significant increase in tear production values evaluated with the Schirmer test under topical anesthesia by at least 2 mm.
3. Significant decrease in the degree of conjunctival hyperemia by at least one point (Efron scale, 0-4).
4. Significant improvement, in at least one point, of the parameters related to the Meibomian glands (Efron scale, 0-4).
5. 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).
6. 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.

Secondary endpoints 5

1. Rate of adverse events related to the application of subconjunctival injection of ASC.
2. 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.
3. 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.
4. Search for new biomarkers that can be used to objectively assess the evolution of patients affected by cRHD and with ocular involvement.
5. Percentage of clinical improvement of the lower dose (6.25 millions of ASCs) compared to the higher dose (12.5 millions of ASCs).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacion De Investigacion Biomedica De Salamanca

Sponsor organisation

Fundacion De Investigacion Biomedica De Salamanca

Address

Paseo De San Vicente 58-182

City

Salamanca

Postcode

37007

Country

Spain

Scientific contact point

Organisation

Fundacion Instituto De Estudios De Ciencias De La Salud De Castilla Y Leon

Contact name

CT Project manager

Public contact point

Organisation

Fundacion Instituto De Estudios De Ciencias De La Salud De Castilla Y Leon

Contact name

CT Project manager

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications