Clinical Trial to Evaluate Safety and Efficacy of Cell Therapy in Patients With Cicatricial Conjuntivitis.

Study Overview
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Brief Summary
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A phase IIa, open label, non controlled clinical trial to assess the feasibility and safety of allogeneic adipose-derived mesenchymal stem cells (ASC) in the treatment of cicatricial conjunctivitis associated with Lyell's syndrome, Stevens-Johnson's syndrome and mucous membrane pemphigoid with ocular involvement

Detailed Description
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A multicentre, nationwide clinical trial will be performed. 20 patients fulfilling eligibility criteria will be included in two different dose level cohorts: the first 10 patients included will receive a single cell application and the remainder 10 will be administered 2 cell applications separated by 15 days. The investigational drug consists of locally administered, expanded, allogeneic adipose-derived adult mesenchymal stem cells (ASCs), at a dose of 5 million cells per ml (0,5 ml to be infused per quadrant) Study cronogram: recruitment is estimated to take 8 months, and follow-up period will be 12 months.

Official Title
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Phase IIa Multicenter Clinical Trial to Determine the Feasibility and Safety of the Use of Adipose-derived Mesenchymal Stem Cells (ASC) in the Treatment of Patients With Cicatricial Conjunctivitis Associated With Lyell's Syndrome, Stevens-Johnson Syndrome and Pemphigoid of the Mucous Membranes With Ocular Involvement.

Conditions
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Chronic Conjunctivitis, Stevens-Johnson Syndrome, Lyell Syndrome, Pemphigoid

Intervention / Treatment
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* Drug: Single Dose
* Drug: Double Dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women over 18 years of age. Diagnosis of ocular pemphigoid in Foster stages I-IIcIIIb (2) or diagnosis of recurrent chronic or episodic inflammation accompanied by cicatricial conjunctivitis of the mucous membranes with ocular involvement after the acute phase of Stevens-Johnson Syndrome or Lyell Syndrome with insufficient disease control or inaceptable toxicity or impossibility to administer usual care treatments (according to physician or patient criteria) In the case of women of childbearing age, who are willing to use an effective contraceptive method during the period of participation in the study Consent to participate and signature of the informed consent Exclusion Criteria: Signs of active infection on the ocular surface. History of neoplasms in the last 5 years. except for epithelial basal or squamous cell carcinoma Allergy to local anesthetics Patients who have participated in another clinical trial with medication during the 90 days prior to signing the IC Medical or psychiatric illness of any kind that, in the opinion of the investigator, may be a reason for exclusion from the study. Congenital or acquired immunodeficiencies. Major surgery or serious trauma of the subject in the semester prior to signing the IC. Pregnant or lactating women. Impossibility or refusal to carry out the follow-up required in the study by the patient

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: 2 consecutive cohorts will be included in order of recruitment. the first 10 patients will receive 1 single dose and the second 10 patients will receive 2 doses separated by 15 days
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single dose Allogenic Adiposse derived mesenchimal stem cells<br>Allogenic Adiposse derived mesenchimal stem cells (MSC) Dose: 12,5 million cells | Drug: Single Dose<br>* Single Dose: Administration of 12,5 million allogeneic mesenchymal stem cells derived from adipose tissue by subcnjunctival injection and topical conjunctival injection.<br>|
| Experimental: Double dose Allogenic Adiposse derived mesenchimal stem cells<br>Allogenic Adiposse derived mesenchimal stem cells (MSC) Dose: 12,5 million cells at day 0 and 12,5 million cells at day 14 | Drug: Double Dose<br>* Repetead Dose: Administration of 2 doses, separated by 14 days, of 12,5 million allogeneic mesenchymal stem cells derived from adipose tissue by subcnjunctival injection and topical conjunctival injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of complications | Percentage of complications related to anesthesia, administration of investigational medicinal product and postoperative period. | Through study completion, an average of 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Signs improvement | Changes from baseline in scarring conjunctivitis rating scale | At 7 days (and 21 days in the 2-dose group), 4 weeks, 12 weeks, 24 weeks and 52 weeks | 
| Symptom improvement | Changes from baseline in Ocular Surface Disease Index (OSDI) questionnaire (0-48). The lower the rate obtained in the score, better the outcome. | At 7 days (and 21 days in the 2-dose group), 4 weeks, 12 weeks, 24 weeks and 52 weeks | 
| Visual acuity improvement | Changes from baseline in Early Treatment Diabetic Retinopathy Study (ETDRS) (0-1,2). The higher the rate obtained in the score, better the outcome. | At 7 days (and 21 days in the 2-dose group), 4 weeks, 12 weeks, 24 weeks and 52 weeks | 
| changes in quality of life | Changes from baseline using the specific National Eye Institute-Visual Function Questionnaire 25 (NEI-VFQ-25) (0-100). The value of 0 is the lowest and 100 the best possible | At 7 days (and 21 days in the 2-dose group), 4 weeks, 12 weeks, 24 weeks and 52 weeks | 
| evolution of the conjunctival flora | variation in the number and type of microorganisms in the conjunctival exudates, performing cultures and PCR herpes viridae | At 7 days (and 21 days in the 2-dose group), 4 weeks, 12 weeks, 24 weeks and 52 weeks |