Total Bilateral Limbal Cell DeficiencyPhase 1/2FEMJANCT03949881
Cultured Autologous Oral Mucosa Epithelial Sheet for the Treatment of Bilateral Limbal Stem Cell Deficiency
A Phase 1/2 study testing FEMJA transplatation in people with Total Bilateral Limbal Cell Deficiency, run by Hospices Civils de Lyon at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Total Bilateral Limbal Cell Deficiency
- What is being tested?
- FEMJA transplatation
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteFrance
- Study dates
- 13 Nov 2020to 13 May 2031
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 26Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
Ophthalmology department, Edouard Herriot hospital, Hospices Civils de Lyon
Lyon, 69003
Carole BURILLON, MD, 472.11.62.17 ext. +33, carole.burillon@chu-lyon.fr
Carole BURILLON, MD
About this study
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 "
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.
Read more
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.
- Conditions
- Total Bilateral Limbal Cell Deficiency
- Being tested
- FEMJA transplatation
- Keywords
- FEMJA transplantation, Epithelial jugal mucosa sheet, Limbal Stem-Cell Deficiency
- Medical subject headings
- Limbal Stem Cell Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FEMJA transplatationBiological
Also called Cultivated oral mucosal epithelium transplantation
The cultivated oral mucosal epithelium will be directly grafted onto the corneal stroma. The sheet is grafted without suture onto the exposed stromal bed after removal of the conjunctiva and fibrosis from the cornea. The grafted corneal surface is then covered with a soft permanent contact lens for protection during healing (between 3 to 15 days, according to tolerance) If the stroma appears opaque because of deep stromal scars a corneal allograft will be performed 12 months after FEMJA transplantation.
| Study group | Role | What they receive |
|---|---|---|
| FEMJA transplatation | Experimental | FEMJA epithelium is obtained by culturing oral mucosal epithelial cells without any need of support substrates, or carriers, and the transparent fabricated sheets show strong, rapid adhesion on corneal stroma in vivo, without any need for suturing.
The cultivated oral mucosal epithelium will be directly grafted onto the corneal stroma. The sheet is grafted without suture onto the exposed stromal bed after removal of the conjunctiva and fibrosis from the cornea. The grafted corneal surface is then covered with a soft permanent contact lens for protection during healing (between 3 to 15 days, according to tolerance) If the stroma appears opaque because of deep stromal scars a corneal allograft will be performed 12 months after FEMJA transplantation. Receives: Biological: FEMJA transplatation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with any improvement in visual acuity
Visual acuity measured at baseline (preoperative status) and 24 months after a jugal mucosa epithelial cell sheet transplantation (FEMJA transplantation), according to the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. ETDRS LogMAR tests allow measurement of very low visual acuity.
Measured: 24 months after FEMJA transplantation
Secondary outcomes (7)
Number of successful FEMJA transplantations
A success is defined by obtaining at least one FEMJA sheet that could be grafted without perforating it
Measured: During 1 day of transplantation
Number of adverse events related to the procedure
Adverse events related to the procedure; especially expected adverse events: inflammation, infection, and perforation.
Measured: Up to 24 months after FEMJA transplantation
Improvement in physical signs
Any improvement from inclusion in physical signs measured with a slit lamp, in terms of: persistant epithelial defect; superficial punctate epithelial keratitis; and conjunctival epithelium on cornea.
Measured: 6 months, 12 months, 18 months and 24 months after FEMJA transplantation
Improvement in neovascularization
Number of patients with a decrease in the number of vascular pediculus near the limbus and their activity, compared to inclusion.
Measured: 6 months, 12 months, 18 months and 24 months after FEMJA transplantation
Improvement in symptoms, i.e. functional signs
Number of patients with an improvement in functional signs measured with Likert scales by self-reporting from the patient, in terms of: photophobia, eye dryness, and pain, compared to inclusion.
Measured: 6 months, 12 months, 18 months and 24 months after FEMJA transplantation
Corneal graft rejection
Among patients with secondary corneal graft, number of patients with graft rejection defined by intraocular pression (≥ 22mmHg) and significant increase in the thickness of the stroma of the cornea compared to the measured value just post graft on corneal topography.
Measured: 24 months after FEMJA transplantation
Correlation between biological FEMJA characteristics and changes in visual acuity
FEMJA characteristics (extraction yield, percentage of proliferative epithelial cells) will be compared according to the clinical response for changes in visual acuity.
Measured: 24 months after FEMJA transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2019
- Study start13 Nov 2020
- Primary completion13 May 2031 (estimated)
- Study completion13 May 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Total Bilateral Limbal Cell DeficiencyStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03949881
- Sponsor's protocol ID
- 69HCL19_0032
- Acronym
- FEMJA
- Status last verified
- Dec 2025
- First submitted
- 13 May 2019
- Last updated
- 16 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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 "
- ClinicalTrials.gov ID
- NCT03949881
- Acronym / sponsor ID
- FEMJA / 69HCL19_0032
- Conditions
- Total Bilateral Limbal Cell Deficiency
- Keywords
- FEMJA transplantation, Epithelial jugal mucosa sheet, Limbal Stem-Cell Deficiency
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- 13 Nov 2020 (actual)
- Primary completion
- 13 May 2031 (estimated)
- Study completion
- 13 May 2031 (estimated)
- First posted
- 14 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| FEMJA transplatation | Experimental | Biological: FEMJA transplatationFEMJA epithelium is obtained by culturing oral mucosal epithelial cells without any need of support substrates, or carriers, and the transparent fabricated sheets show strong, rapid adhesion on corneal stroma in vivo, without any need for suturing. The cultivated oral mucosal epithelium will be directly grafted onto the corneal stroma. The sheet is grafted without suture onto the exposed stromal bed after removal of the conjunctiva and fibrosis from the cornea. The grafted corneal surface is then covered with a soft permanent contact lens for protection during healing (between 3 to 15 days, according to tolerance) If the stroma appears opaque because of deep stromal scars a corneal allograft will be performed 12 months after FEMJA transplantation. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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)
Key exclusion criteria (26 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FEMJA transplatationAlso: Cultivated oral mucosal epithelium transplantationThe cultivated oral mucosal epithelium will be directly grafted onto the corneal stroma. The sheet is grafted without suture onto the exposed stromal bed after removal of the conjunctiva and fibrosis from the cornea. The grafted corneal surface is then covered with a soft permanent contact lens for protection during healing (between 3 to 15 days, according to tolerance) If the stroma appears opaque because of deep stromal scars a corneal allograft will be performed 12 months after FEMJA transplantation. | Biological | FEMJA transplatation |
Primary outcome
Number of patients with any improvement in visual acuity
Time frame: 24 months after FEMJA transplantation
Visual acuity measured at baseline (preoperative status) and 24 months after a jugal mucosa epithelial cell sheet transplantation (FEMJA transplantation), according to the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. ETDRS LogMAR tests allow measurement of very low visual acuity.
7 secondary outcomes
Number of successful FEMJA transplantations
Time frame: During 1 day of transplantation
Number of adverse events related to the procedure
Time frame: Up to 24 months after FEMJA transplantation
Improvement in physical signs
Time frame: 6 months, 12 months, 18 months and 24 months after FEMJA transplantation
Improvement in neovascularization
Time frame: 6 months, 12 months, 18 months and 24 months after FEMJA transplantation
Improvement in symptoms, i.e. functional signs
Time frame: 6 months, 12 months, 18 months and 24 months after FEMJA transplantation
Corneal graft rejection
Time frame: 24 months after FEMJA transplantation
Correlation between biological FEMJA characteristics and changes in visual acuity
Time frame: 24 months after FEMJA transplantation
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Dec 2025.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing FEMJA transplatation in people with Total Bilateral Limbal Cell Deficiency, run by Hospices Civils de Lyon at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 16 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Carole BURILLON, MD (472.11.62.17 ext. +33, carole.burillon@chu-lyon.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of patients with any improvement in visual acuity (time frame: 24 months after FEMJA transplantation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Dec 2025.