Evaluation of Allogenic Mesenchymal Stem Cell (MSC) Injec... | NCT06905834

NCT06905834

ID	Type	Description	Link
2024-519772-10-00	EU Trial (CTIS) Number

Status Module

Name	Class
Spanish Clinical Research Network - SCReN	NETWORK
Instituto Universitario de Oftalmobiología Aplicada (Institute of Applied Ophthalmobiology) - IOBA	OTHER

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
6.25 million ASCs / 2,5ml of Ringer Lactato + 1% of HSA.	Experimental	6.25 million mesenchymal cells will be injected subconjunctivally into each subject in the group. These cells will be in a 2.5 mL suspension of Lactated Ringer's solution, to which 1% HSA will have been added beforehand.	Drug: Subconjuntival injection of expanded allogenic adult adipose tissue-derived mesenchymal stem cells (ASC
12.5 million ASCs / 2,5 ml of Ringer Lactato + 1% of HSA.	Experimental	12.5 million mesenchymal cells will be injected subconjunctivally into each subject in the group. These cells will be in a 2.5 mL suspension of Lactated Ringer's solution, to which 1% HSA will have been added beforehand.	Drug: Subconjuntival injection of expanded allogenic adult adipose tissue-derived mesenchymal stem cells (ASC

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Subconjuntival injection of expanded allogenic adult adipose tissue-derived mesenchymal stem cells (ASC	Drug	Subconjunctival injection is a widely used technique in ophthalmology due to its effectiveness, minimal invasiveness, and ease of administration. In a subconjunctival injection the cells adult adipose tissue-derived mesenchimal cells are delivered into the subconjunctival space, the area between the conjunctiva and sclera.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change in the integrity of the ocular surface	Significant improvement in the integrity of the ocular surface, measured by corneal staining with fluorescein. 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). If an epithelial defect is present, a reduction of at least ¾ of its initial size is required. The Oxford scale is a grading system used to assess ocular surface damage based on corneal and conjunctival staining with fluorescein or lissamine green dyes. It is commonly used to evaluate conditions like dry eye disease and superficial punctate keratitis (SPK). The scale ranges from 0 to 5, where 0 represents no staining (healthy eye) and 5 indicates severe staining and damage.	six and twelve months from start of treatment
Change in tear production	Significant increase in tear production, evaluated using the Schirmer test with topical anesthesia, by at least 2 mm. The Schirmer test is a diagnostic test used to measure tear production and assess dry eye syndrome. It evaluates whether the eyes produce enough tears to keep them properly lubricated. Results are as follows: Normal: ≥10 mm of wetting after 5 minutes Mild to moderate dry eye: 5-10 mm Severe dry eye: ≤5 mm	six and twelve months from start of treatment
Change in the degree of conjunctival hyperemia	Significant reduction in the degree of conjunctival hyperemia by at least one point (Efron scale, 0-4). The Efron Scale is a clinical grading scale used by eye care professionals to assess the severity of contact lens complications and ocular surface conditions. It provides a standardized way to evaluate changes in the cornea and conjunctiva. The scale ranges from 0 to 4, where: Grade 0 = Normal (No signs of damage) Grade 1 = Trace (Mild changes, barely noticeable) Grade 2 = Mild (Early signs of irritation or damage) Grade 3 = Moderate (Significant changes, requires attention) Grade 4 = Severe (Serious complications, may need treatment)	six and twelve months from start of treatment

Secondary Outcomes

Measure	Description	Time Frame
Rate of adverse events related to the administration of subconjunctival ASC injection.	The investigator will record in the eCRF and communicate to the sponsor or to the person assuming the tasks delegated by the sponsor, the adverse events (AEs) that are considered of special interest occurring during the study as soon as possible, and no later than 15 days after becoming aware of them. The AEs considered of special interest are: Immunogenicity reactions and their consequences. Adverse events possibly due to unexpected reactions such as hypersensitivity, immunological, toxic reactions, and migration of cells from the application site. Adverse events related to product failure that may be associated with the production process or with the quality of the investigational product.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Patients over 18 years of age who understand and sign the informed consent form.
Diagnosis of severe GVHD (graft versus host disease) according to NIH criteria (revised by Lee SJ in 2017) with ocular involvement in the form of severe SOD (severe ocular disease) in both eyes for more than 3 months, objectively defined as superficial punctate keratitis >2 on the Oxford scale (range 0-5) and/or the presence of epithelial defect, and subjectively as severe symptoms, >33 points on the OSDI questionnaire (0-100).
Patients must have previously been treated for at least three months with blood derivatives and/or insulin eye drops and topical cyclosporine or tacrolimus (unless any of these treatments were not tolerated and had to be discontinued).
Patients must be using ocular lubricants at least 4 times a day and, despite this, still meet the criteria for severe SOD as outlined in point 2.
Patients on low doses of topical corticosteroids for maintenance should have a stable dose for at least one month prior to inclusion.
The dose and frequency of all topical medications the patient begins the trial with must remain unchanged throughout the duration of the trial, unless otherwise judged by the investigator.
The chronic GVHD systemic treatment should be stable regarding the use of systemic immunosuppressors for at least one month prior to patient inclusion or before starting treatment.
Negative result in the urine pregnancy test at the baseline visit for women of childbearing age. Subjects must be advised to use contraceptive methods during their participation in the clinical trial and undergo a new pregnancy test at the treatment visit if more than 28 days have passed since the baseline visit.

Exclusion Criteria:

Uncontrolled systemic disease or any condition that, in the medical judgment, could put the patient at risk or affect the interpretation of the results.
Uncontrolled systemic GVHD.
Active ocular infection.
Ocular surgery within the last 3 months.
Initiation of topical therapies for SOD indicated in the inclusion criteria less than 3 months prior to inclusion.
Start of topical corticosteroid use within 4 weeks prior to inclusion.
Cognitive impairments that could interfere with study compliance.
Pregnant women or women during the lactation period.

Name	Role	Phone	Extension	Email
Esperanza Lopez Franco PhD, PhD in Molecular Biology	Contact	+34923291200	55779	uicec.coordinacion@ibsal.es
Fátima Macho Sánchez-Simón, PhD in Neuroscience	Contact	+34923291200	55145	uicec-admon@ibsal.es

Name	Affiliation	Role
Fermín Sánchez-Guijo Martín MD, PhD, Medical Degree in Haematology	Centro Asistencial Universitario de Salamanca (CAUSA)	Study Director
Lourdes Vázquez López MD, PhD, Medical Degree in Haematology	Centro Asistencial Universitario de Salamanca (CAUSA)

IPD Sharing Statement Module

ID	Term
D015352	Dry Eye Syndromes
D006086	Graft vs Host Disease

ID	Term
D007766	Lacrimal Apparatus Diseases
D005128	Eye Diseases
D007154	Immune System Diseases