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

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.

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

Study Overview

• Status: Active, not recruiting
• Conditions: Stevens-Johnson Syndrome; Lyell Syndrome; Pemphigoid; Chronic Conjunctivitis
• Intervention / Treatment: Drug: Single Dose; Drug: Double Dose

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Lucia Llanos; Phone Number: 3245 91 5504800; Email: lucia.llanos@quironsalud.es
• Study Contact Backup: Name: Eva Cerezo; Phone Number: 3214 91 5504800; Email: eva.cerezo@quironsalud.es

Study Locations

• Spain
  • Córdoba, Spain, 14012
    • Hospital La Arruzafa
  • Madrid, Spain, 28040
    • Hospital Universitario Fundacion Jimenez Diaz
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Maranon
  • Valladolid, Spain, 47003
    • Hospital Clínico Universitario de Valladolid
  • Asturias
    • Oviedo, Asturias, Spain, 33012
      • Instituto Oftalmológico Fernández - Vega
  • Bizkaia
    • Barakaldo, Bizkaia, Spain, 48903
      • Hospital Universitario de Cruces
  • Ciudad Real
    • Alcázar De San Juan, Ciudad Real, Spain, 13600
      • Hospital General La Mancha Centro

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Men and women over 18 years of age.
2. 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)
3. 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
4. Consent to participate and signature of the informed consent

Exclusion Criteria:

1. Signs of active infection on the ocular surface.
2. History of neoplasms in the last 5 years. except for epithelial basal or squamous cell carcinoma
3. Allergy to local anesthetics
4. Patients who have participated in another clinical trial with medication during the 90 days prior to signing the IC
5. Medical or psychiatric illness of any kind that, in the opinion of the investigator, may be a reason for exclusion from the study.
6. Congenital or acquired immunodeficiencies.
7. Major surgery or serious trauma of the subject in the semester prior to signing the IC.
8. Pregnant or lactating women.
9. Impossibility or refusal to carry out the follow-up required in the study by the patient

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single dose Allogenic Adiposse derived mesenchimal stem cells; Allogenic Adiposse derived mesenchimal stem cells (MSC) Dose: 12,5 million cells	Drug: Single Dose; Single Dose: Administration of 12,5 million allogeneic mesenchymal stem cells derived from adipose tissue by subcnjunctival injection and topical conjunctival injection.
Experimental: Double dose Allogenic Adiposse derived mesenchimal stem cells; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz
• Collaborators: Effice Servicios Para la Investigacion S.L.
• Investigators: Principal Investigator: Nicolás Alejandre Alba, Hospital Fundación Jiménez Díaz

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2022
• Primary Completion (Estimated): February 1, 2024
• Study Completion (Estimated): February 1, 2024

Study Registration Dates

• First Submitted: August 22, 2022
• First Submitted That Met QC Criteria: August 26, 2022
• First Posted (Actual): August 29, 2022

Study Record Updates

• Last Update Posted (Actual): November 14, 2023
• Last Update Submitted That Met QC Criteria: November 13, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Pathologic Processes; Skin Diseases; Immune System Diseases; Autoimmune Diseases; Eye Diseases; Disease; Stomatognathic Diseases; Mouth Diseases; Hypersensitivity; Erythema; Skin Diseases, Vesiculobullous; Conjunctival Diseases; Dermatitis; Drug-Related Side Effects and Adverse Reactions; Hypersensitivity, Delayed; Stomatitis; Drug Eruptions; Erythema Multiforme; Drug Hypersensitivity; Syndrome; Pemphigoid, Bullous; Stevens-Johnson Syndrome; Conjunctivitis
• Other Study ID Numbers: CELOPHIN

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No