Cell Therapy in Failure Syndromes in Limbal Stem Cells
Condition: Limbal Deficiency
Study type: Interventional
Phase: Phase 2

Summary: 
      Transplantation of allogeneic or autologous limbal epithelial stem cells cultured on human
      amniotic membrane with no feeders in eyes with total limbal deficiency. Prospective
      non-comparative monocentric study.
    

Detailed description: 
      The limbal stem cell deficiency syndrome is characterized by invasion of the corneal surface
      by an epithelium with a conjunctival differentiation, and, clinically, by opacification and
      vascularization of the corneal epithelium with impaired corneal epithelial cicatrisation and
      corneal ulcers that may lead to corneal perforation. When total, the limbal deficiency
      syndrome is the cause of major disability. Vision decreases largely under the legal threshold
      of blindness. Overall, the most frequent etiology is by far the complete loss of limbal stem
      cells induced by severe ocular burns. Until a rather recent date, no treatment was possible
      in this pathology. Progress in the comprehension of the physiology of the corneal epithelium
      renewal made it possible to introduce a therapeutic approach, i.e., transplantation of
      cultured limbal stem cells retrieved from the healthy contralateral eye (autograft,
      unilateral diseases) or from a cadaveric donor eye (allograft, bilateral diseases or unique
      eye). Techniques of cell therapy were first described in Italy, Asia and in the USA with
      positive clinical results. They have all different processes for preparing the cell product
      to be transplanted and none answers the safety criteria required by the French legislation.
      The investigators developed a process for preparing a cell therapy product which was accepted
      by the French regulation agency (AFSSaPS) for a clinical trial (TC181) which began in 2007.
      The aims of the study are (1) evaluation of the clinical results of this technique in terms
      of improvement of visual function, reduction in the handicap, improvement of the anatomical
      condition of the ocular surface and restitution of the physiological function of the limbal
      epithelium and (2) evaluation of its possible side effects. It is a biphasic monocentric
      non-comparative prospective study including, according to the clinical responses observed
      during the first phase (plane of Gehan, ß = 10%), from 15 to 50 voluntary patients with
      unilateral or bilateral total limbal deficiency. Patient follow-up is 3 years. The expected
      minimal success rate is 20% for allografts and 40% for the autografts. Monitoring is ensured
      by URC-Est. The grafts are prepared by culture of autologous or allogeneic limbal epithelial
      cells from limbal explants on human amniotic membrane. The medical safety requirements
      relating to transplantation of tissues and cells are reached and the cell therapy products
      are secured at each stage of their preparation by conventional bacteriological and fungal
      tests and viral and bacterial PCR. The graft quality is controlled before transplantation.
      The main outcome measure is survival of the grafted epithelium (Kaplan-Meier method) defined
      by absence of recurrence of the clinical signs of limbal deficiency (opacification of the
      corneal epithelium, irregularity of the corneal epithelium, surface corneal vascularization)
      in the central cornea. The expected repercussions are (1) restitution of a limbal epithelial
      function allowing a clear corneal epithelium to be obtained, with no superficial
      vascularization nor chronic epithelial defects, (2) improvement of vision in blind patients,
      and (3) obtaining a vision higher than the legal threshold of blindness after cell therapy or
      after subsequent corneal transplantation. If the clinical trial makes it possible to show the
      effectiveness of this cell therapy technique, a request for authorization of process will be
      made at AFSSaPS for routine use.
    

Intervention name(s): epithelial stem cells cultured; transplantation of cultured cells
Intervention type(s): Biological; Procedure
Intervention description(s): transplantation of allogeneic or autologous limbal epithelial stem cells cultured on human amniotic membrane with no feeders; transplantation of allogeneic or autologous limbal epithelial stem cells cultured on human amniotic membrane with no feeders
Intervention model: Single Group Assignment
Intervention model description: Prospective Phase II Interventional Clinical Trial (Transplantation of Allogeneic or Autologous Limbal Epithelial Stem Cells Cultured on Human Amniotic Membrane with no Feeders)
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Cell therapy; Limbal deficiency; Limbal stem cell; Transplantation