Clinical trial NCT03949881: Cultured Autologous Oral Mucosa Epithelial Sheet for the Treatment of Bilateral Limbal Stem Cell Deficiency
Official title: Cultured Autologous Oral Mucosa Epithelial Sheet for the Treatment of Bilateral Limbal Stem Cell Deficiency FEMJA for " Feuillet Epithélial de Muqueuse Jugale Autologue "
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Total Bilateral Limbal Cell Deficiency
Keywords: FEMJA transplantation
Epithelial jugal mucosa sheet
Limbal Stem-Cell Deficiency
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2019-05-14
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Some severe ocular burns or other rare ocular pathologies can be associated with a total loss of corneal epithelial stem cells (i.e. Limbal Stem Cell Deficiency - LSCD), which leads to cornea invasion by the conjunctiva and a subsequent opacification. When LSCD is total and bilateral, both eyes are affected leading to full blindness and a poor quality of life, with a paradoxical photophobia that may be painful. Fewer than 100 patients bear this rare condition in France.

When patients suffer from total and bilateral LSCD, no treatment has been proven to provide clinical benefits: contralateral limbus is unavailable for autologous limbus graft or autologous limbal stem cells culture; allogeneic limbus graft requires immunosuppressive treatment leading to too important serious adverse effects compared to the expected benefit, and does not last long (\< 2 years); and allogenic cornea transplantation is impossible since always rejected due to neovascularization.

A new way to treat these patients is to cultivate autologous corneal-like epithelium, and to graft it in order to restore transparency and to allow, if needed, a complementary corneal graft. Such an epithelium can be produced from autologous jugal mucosa cells. Epithelial jugal mucosa sheets transplantation has been assessed in a phase I/II clinical trial on 26 patients which showed that it is well-tolerated and effective but the culture technology used in this clinical trial is no longer available. A new enzymatic detachment process has been developed by the Hospices Civils de Lyon. Proof of concept was obtained from both in vitro and ex vivo studies: detachment with Collagenase at 0.5 mg/mL doesn't damage basement membrane proteins, so collagenase 0.5mg/mL-detached FEMJA were found to adhere, continue to ensure renewal of the differentiated epithelium 15 days after grafting onto an ex vivo porcine de-epitheliazed stroma model.

Considering these results, we aim to perform a clinical trial in order to evaluate tolerance and efficacy of the autologous jugal mucosa cell sheet (Feuillets Epithéliaux de Muqueuse Jugale Autologue - FEMJA) cultured with this innovative process.


Eligibility criteria: Inclusion Criteria:

* Male or female aged ≥ 18 years
* Signed and dated informed consent for participation in the study
* Total bilateral limbal stem-cell deficiency
* Caused by thermal or chemical burn, cornea transplantation, and other bilateral disorders of the ocular surface
* Severe loss of vision (\<2/10 on decimal scale or/and EDTRS)
* The subject must be covered by a social security system

Exclusion Criteria

* Eye inflammation
* Strictly unilateral ocular affliction
* Acute systemic infection, objectified during consultation by the investigator and on the following paraclinical parameter: C Reactive Protein rate
* History of acute phase of ocular inflammation in the previous year
* History of neoplasic disease
* Glaucoma defined as intra ocular pressure (air tonometer and applanation tonometer) ≥ 22mmHg
* Total symblepharon (comprising eyelid aperture): impossibility to open the 2 eyes
* History of hyper sensibility or allergy to antibiotics or serum
* Women who are or may be pregnant or breastfeading
* Patients with any active infectious disease (HBV, HCV, HIV, HTLV-1 and syphilis)
* Patients who are otherwise ineligible for participation in the study in the opinion of the investigator.
* Delay of less than one year after chemical or thermal burns
* Person under judicial protection
* Contraindication related to anesthesia
* Contraindication to fluoresceine
* Oral mucosa tumor, pharynx or larynx tumor
* Fungal or viral infection of the ENT area
* Bacteria infection of the oral mucosa, pharynx or larynx.
* Hypersensitivity to ofloxacin (or other quinolone drugs), fluorometholone or betamethasone.
* Hypersensitivity to one of the excipients of the eye drops used: Monosodium phosphate, anhydrous disodium phosphate, polysorbate 80, sodium chloride, sodium edetate, polyvinyl alcohol, benzalkonium chloride, hydroxypropylmethylcellulose, hydrochloric acid, sodium hydroxide, lactose, cellulose, crospovidone, aspartam, magnesium stearate,
* Phenylketonuria
* Psychotic states not yet controlled by treatment;
* Vaccination with a live vaccine
* Bacterial, fungal, myco-bacterial infection of eye structures.
* Some evolving viral infections (including hepatitis, herpes, chickenpox, shingles) or other viral infections of the cornea or conjunctiva (except for a keratitis to Herpes zoster).
* Patients treated with Class IA or III antiarrhythmics, tricyclic antidepressants, macrolides and antipsychotics

Primary outcomes:
measure: Number of patients with any improvement in visual acuity
timeFrame: 24 months after FEMJA transplantation
Secondary outcomes:
measure: Number of successful FEMJA transplantations
timeFrame: During 1 day of transplantation
measure: Number of adverse events related to the procedure
timeFrame: Up to 24 months after FEMJA transplantation
measure: Improvement in physical signs
timeFrame: 6 months, 12 months, 18 months and 24 months after FEMJA transplantation
measure: Improvement in neovascularization
timeFrame: 6 months, 12 months, 18 months and 24 months after FEMJA transplantation
measure: Improvement in symptoms, i.e. functional signs
timeFrame: 6 months, 12 months, 18 months and 24 months after FEMJA transplantation
measure: Corneal graft rejection
timeFrame: 24 months after FEMJA transplantation
measure: Correlation between biological FEMJA characteristics and changes in visual acuity
timeFrame: 24 months after FEMJA transplantation
Other outcomes:
Locations:
city: Lyon
country: France
facility: Ophthalmology department, Edouard Herriot hospital, Hospices Civils de Lyon
Study officials:
References: