SYMBOL CLINICAL : Treatment of severe ocular chemical burns by subconjunctival injection of allogeneic mesenchymal stem cells: a multicentre, single-arm, open-label phase II trial

2023-509713-37-00 Protocol SYMBOL CLINICAL Therapeutic exploratory (Phase II) Authorised, recruitment pending

Status Authorised, recruitment pending · 1 EU/EEA countries · 13 sites · Protocol SYMBOL CLINICAL

Overview

Sponsor-declared trial summary

Phase Therapeutic exploratory (Phase II)
Status Authorised, recruitment pending
Participants planned 21
Countries 1
Sites 13

Patient with severe eye chemical burns

To evaluate the efficacy of a protocol of subconjunctival injection of allogeneic BM-MSC in the acute phase of a severe chemical burn of the ocular surface (stage VI according to the Dua classification) on the preservation of the eyeball 6 months after the first injection.

Key facts

Sponsor
Hopital Fondation Adolphe De Rothschild
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Eye Diseases [C11]
Decision date (initial)
2025-12-09
Transition trial
No
Low-intervention
No
Rare-disease indication
Yes
Vulnerable population
No
Funding sources
Ministry of health and prevention

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

To evaluate the efficacy of a protocol of subconjunctival injection of allogeneic BM-MSC in the acute phase of a severe chemical burn of the ocular surface (stage VI according to the Dua classification) on the preservation of the eyeball 6 months after the first injection.

Secondary objectives 9

  1. To describe, in the acute phase of a severe chemical burn of the ocular surface (stage VI according to the Dua classification), the impact of a protocol of subconjunctival injection of allogeneic BM-MSC on : Complete epithelialisation of the cornea at 3, 6, 9 and 12 months after the first injection
  2. To describe, in the acute phase of a severe chemical burn of the ocular surface (stage VI according to the Dua classification), the impact of a protocol of subconjunctival injection of allogeneic BM-MSC on : The extent of limbal stem cell deficiency at 3, 6, 9 and 12 months after the first injection
  3. To describe, in the acute phase of a severe chemical burn of the ocular surface (stage VI according to the Dua classification), the impact of a protocol of subconjunctival injection of allogeneic BM-MSC on : Conjunctival fibrosis at 3, 6, 9 and 12 months post-injection
  4. To describe, in the acute phase of a severe chemical burn of the ocular surface (stage VI according to the Dua classification), the impact of a protocol of subconjunctival injection of allogeneic BM-MSC on : Inflammation of the ocular surface at 2, 6 and 12 months after the first injection
  5. To describe, in the acute phase of a severe chemical burn of the ocular surface (stage VI according to the Dua classification), the impact of a protocol of subconjunctival injection of allogeneic BM-MSC on : Visual acuity 12 months after the first injection
  6. To describe, in the acute phase of a severe chemical burn of the ocular surface (stage VI according to the Dua classification), the impact of a protocol of subconjunctival injection of allogeneic BM-MSC on : Corneal thickness 12 months after the first injection
  7. To describe, in the acute phase of a severe chemical burn of the ocular surface (stage VI according to the Dua classification), the impact of a protocol of subconjunctival injection of allogeneic BM-MSC on : The number of surgeries performed on the eye included in the 12 months following the first injection
  8. To describe, in the acute phase of a severe chemical burn of the ocular surface (stage VI according to the Dua classification), the impact of a protocol of subconjunctival injection of allogeneic BM-MSC on : The number of days local immunosuppressants were prescribed in the 12 months following the first injection
  9. To describe, in the acute phase of a severe chemical burn of the ocular surface (stage VI according to the Dua classification), the impact of a protocol of subconjunctival injection of allogeneic BM-MSC on : Tolerance

Conditions and MedDRA coding

Patient with severe eye chemical burns

Study design 1 period

#TitleAllocationBlindingRoles blindedArms
1 SYMBOL Treatment of severe ocular chemical burns by subconjunctival injection of allogeneic mesench
a multicentre, single-arm, open-label phase II trial
 Not Applicable None

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

  1. Age ≥ 18 years
  2. Uni or bilateral chemical burn of the ocular surface
  3. Severe ocular burn of at least one eye: stage VI of Dua severity classification (involving the entire limbus and conjunctiva)
  4. Time between burn and inclusion ≤ 15 days
  5. Patient having received informed information about the study and having signed a consent to participate in the study
  6. Affiliated or beneficiary of a social security scheme

Exclusion criteria 15

  1. Impending corneal perforation (loss of corneal tissue > 2/3 of corneal thickness)
  2. Ocular infection
  3. Loss of palpebral substance with permanent corneal exposure
  4. Known allergy (hypersensitivity) to human albumin preparations
  5. Known history of total or partial limbic insufficiency
  6. Uncontrolled glaucoma prior to ocular burns
  7. Recipient of an organ or cell transplant
  8. Previous cancer ≤ 5 years
  9. Current treatment with immunosuppressive drugs (systemic corticosteroids, TNFα antagonists, azathioprine, methotrexate, mycophenolate mofetil, etc.)
  10. Adults subject to a legal protection measure (L1121-8) Persons deprived of their liberty by judicial or administrative decision, persons subject to psychiatric care under articles L3212-1 and L3123-1 and persons admitted to a health or social establishment for purposes other than research (L1121-6).
  11. Pregnant or breast-feeding women
  12. Participation in other interventional research (RIPH 1, clinical drug trials, clinical investigations) for the duration of their follow-up.
  13. Secondary exclusion criteria : Grade VI of the Dua classification not confirmed by the expert ophthalmologist at the Hôpital Fondation A. de Rothschild
  14. Secondary exclusion criteria : Patient did not receive subconjunctival injection of allogeneic BM-MSCs
  15. Secondary exclusion criteria : Positive pregnancy test before the first subconjunctival injection of allogeneic BM-MSCs.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Absence of corneal perforation as assessed by the clinician

Secondary endpoints 9

  1. All criteria refer to the eye receiving treatment in the study: Assessed by the clinician using a fluorescein test at the slit lamp examination.
  2. All criteria refer to the eye receiving treatment in the study: Classification by the LSCD international working group
  3. All criteria refer to the eye receiving treatment in the study: Tauber and Foster classification
  4. All criteria refer to the eye receiving treatment in the study: Percentage of HLA-DR positive cells on conjunctival impression cytology
  5. All criteria refer to the eye receiving treatment in the study: Snellen scale
  6. All criteria refer to the eye receiving treatment in the study: OCT of the anterior segment (Optical Coherence Tomography)
  7. All criteria refer to the eye receiving treatment in the study: Collected from the patient's medical file
  8. All criteria refer to the eye receiving treatment in the study: Collected from the patient's medical file
  9. All criteria refer to the eye receiving treatment in the study: Incidence rate, type and severity of adverse events

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Bone marrow-derived Mesenchymal Stromal Cells cryopreserved at passage P2, thawed, washed and syringe-conditioned in 0.9% NaCl - 0.5% human serum albumin injection solution at a dose of 5.10^6 Mesenchymal Stromal Cells

PRD12668956 · Product

Active substance
Allogeneic Bone Marrow-Derived Mesenchymal Stromal Cells
Pharmaceutical form
SUSPENSION FOR INJECTION
Route of administration
SUBCONJUNCTIVAL USE
Max daily dose
5 million organisms/ml million organisms/millilitre
Max total dose
10 million organisms/ml million organisms/millilitre
Max treatment duration
2 Day(s)
Authorisation status
Not Authorised
ATC code
S01XA — OTHER OPHTHALMOLOGICALS
MA holder
ROTHSCHILD FOUNDATION HOSPITAL
Paediatric formulation
No
Orphan designation
No

Auxiliary 11

CHLORHYDRATE D’OXYBUPROCAINE THEA 1,6 mg/0,4 ml, collyre en récipient unidose

PRD316987 · Product

Active substance
Oxybuprocaine Hydrochloride
Pharmaceutical form
EYE DROPS, SOLUTION
Route of administration
OCULAR USE
Max daily dose
1.6 mg milligram(s)
Max total dose
3.2 mg milligram(s)
Max treatment duration
2 Day(s)
Authorisation status
Authorised
ATC code
S01HA02 — OXYBUPROCAINE
Marketing authorisation
365 769-2
MA holder
LABORATOIRES THEA
MA country
France
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

IBUPROFENE ARROW 400 mg, comprimé pelliculé

PRD1751745 · Product

Active substance
Ibuprofen
Substance synonyms
(RS)-2-(4-isobutylphenyl)propionic acid, 2-(4-isobutylphenyl)propionic acid
Pharmaceutical form
FILM-COATED TABLET
Route of administration
ORAL USE
Max daily dose
1200 mg milligram(s)
Max total dose
2400 mg milligram(s)
Max treatment duration
2 Day(s)
Authorisation status
Authorised
ATC code
N02B — OTHER ANALGESICS AND ANTIPYRETICS
Marketing authorisation
67539962
MA holder
ARROW GENERIQUES
MA country
France
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

PROPOFOL FRESENIUS 10 mg/ml, émulsion injectable ou pour perfusion

PRD3276624 · Product

Active substance
Propofol
Pharmaceutical form
EMULSION FOR INJECTION/INFUSION
Route of administration
INTRAVENOUS ADMINISTRATION
Max daily dose
30 mg milligram(s)
Max total dose
60 mg milligram(s)
Max treatment duration
2 Day(s)
Authorisation status
Authorised
ATC code
N01AX10 — PROPOFOL
Marketing authorisation
34009 561 001 6 3
MA holder
FRESENIUS KABI FRANCE S.A.S.
MA country
France
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

REMIFENTANIL VIATRIS 2 mg, poudre pour solution injectable ou pour perfusion

PRD11572053 · Product

Active substance
Remifentanil Hydrochloride
Pharmaceutical form
POWDER FOR SOLUTION FOR INJECTION/INFUSION
Route of administration
INTRAVENOUS ADMINISTRATION
Max daily dose
18 mg milligram(s)
Max total dose
36 mg milligram(s)
Max treatment duration
2 Day(s)
Authorisation status
Authorised
ATC code
N01AH06 — REMIFENTANIL
Marketing authorisation
34009 577 289 4 6
MA holder
VIATRIS SANTE
MA country
France
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

DOLIPRANE 500 mg, gélule

PRD429934 · Product

Active substance
Paracetamol
Substance synonyms
ACETAMINOPHEN
Pharmaceutical form
CAPSULE, HARD
Route of administration
ORAL USE
Max daily dose
4 g gram(s)
Max total dose
360 g gram(s)
Max treatment duration
3 Month(s)
Authorisation status
Authorised
ATC code
N02BE01 — PARACETAMOL
Marketing authorisation
34009 560 826 1 2
MA holder
OPELLA HEALTHCARE FRANCE SAS
MA country
France
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

FLUORESCEINE FAURE 0,5 POUR CENT, collyre en solution en récipient unidose

PRD1924320 · Product

Active substance
Fluorescein Sodium
Pharmaceutical form
EYE DROPS, SOLUTION
Route of administration
OCULAR USE
Max daily dose
2 mg milligram(s)
Max total dose
28 mg milligram(s)
Max treatment duration
14 Day(s)
Authorisation status
Authorised
ATC code
S01JA01 — FLUORESCEIN
Marketing authorisation
325 754-4
MA holder
SERB SA
MA country
France
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

BETADINE 5 POUR CENT, solution pour irrigation oculaire en récipient unidose

PRD537151 · Product

Active substance
Povidone, Iodinated
Substance synonyms
Poly(1-(2-oxo-1-pyrrolidinyl)ethylene)iodine complex, POVIDONE IODINE, IODINATED POVIDONE, PVP-IODINE, POVIDONE-IODINE, POLYVIDONE-IODINE, POLYVINYLPYRROLIDONE-IODINE COMPLEX
Pharmaceutical form
SOLVENT FOR SOLUTION FOR INTRAOCULAR IRRIGATION
Route of administration
OCULAR USE
Max daily dose
5 ml millilitre(s)
Max total dose
10 ml millilitre(s)
Max treatment duration
2 Day(s)
Authorisation status
Authorised
ATC code
S01AX18 — POVIDONE-IODINE
Marketing authorisation
34009 562 309 4 5
MA holder
MEDA PHARMA
MA country
France
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

MIDAZOLAM VIATRIS 5 mg/ml, solution injectable ou rectale

PRD11840253 · Product

Active substance
Midazolam
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
INTRAVENOUS ADMINISTRATION
Max daily dose
1 mg milligram(s)
Max total dose
2 mg milligram(s)
Max treatment duration
2 Day(s)
Authorisation status
Authorised
ATC code
N05CD08 — MIDAZOLAM
Marketing authorisation
34009 302 064 7 8
MA holder
VIATRIS SANTE
MA country
France
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

ALBUTEIN 50 g/L, solution pour perfusion

PRD11127876 · Product

Active substance
Human Serum Albumin
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
SUBCONJUNCTIVAL USE
Max daily dose
5 mg milligram(s)
Max total dose
10 mg milligram(s)
Max treatment duration
2 Day(s)
Authorisation status
Authorised
ATC code
B05AA01 — ALBUMIN
Marketing authorisation
34009 550 994 4 4
MA holder
INSTITUTO GRIFOLS, S.A.
MA country
France
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

STERDEX, pommade ophtalmique en récipient unidose

PRD318895 · Product

Active substance
Dexamethasone
Substance synonyms
DEXAMETASONE, DEXAMETHASONUM
Pharmaceutical form
EYE OINTMENT
Route of administration
OCULAR USE
Max daily dose
0.27 mg milligram(s)
Max total dose
0.53 mg milligram(s)
Max treatment duration
2 Day(s)
Authorisation status
Authorised
ATC code
S01CA01 — DEXAMETHASONE AND ANTIINFECTIVES
Marketing authorisation
34009 313 841 4 4
MA holder
LABORATOIRES THEA
MA country
France
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

PARACETAMOL AGUETTANT 10 mg/ml, solution pour perfusion

PRD10481956 · Product

Active substance
Paracetamol
Substance synonyms
ACETAMINOPHEN
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS ADMINISTRATION
Max daily dose
1 g gram(s)
Max total dose
1 g gram(s)
Max treatment duration
2 Day(s)
Authorisation status
Authorised
ATC code
N02BE01 — PARACETAMOL
Marketing authorisation
3400957691073
MA holder
LABORATOIRE AGUETTANT
MA country
France
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Hopital Fondation Adolphe De Rothschild

7 Total trials 5 Recruiting 1 Ended
Academic / Non-commercial
Sponsor organisation
Hopital Fondation Adolphe De Rothschild
Address
25 Rue Manin
City
Paris
Postcode
75019
Country
France

Scientific contact point

Organisation
Hopital Fondation Adolphe De Rothschild
Contact name
Clinical research department

Public contact point

Organisation
Hopital Fondation Adolphe De Rothschild
Contact name
Clinical research department

Locations

1 EU/EEA country · 13 investigational sites

By country

CountryMS statusPlanned subjectsSites
France Authorised, recruitment pending 21 13
Rest of world — 0 —

Investigational sites

France

13 sites · Authorised, recruitment pending
Centre Hospitalier National d'Ophtalmologie des Quize-Vingts
Ophtalmology, 28 Rue De Charenton, 75012, Paris
Centre Hospitalier National d'Ophtalmologie des Quize-Vingts
Ophtalmology, 28 Rue De Charenton, 75012, Paris
Centre Hospitalier Regional De Marseille
Ophtalmology, 144 Rue Saint Pierre, 13005, Marseille
Pellegrin Hospital
Ophtalmology, Place Amelie Raba Leon, 33000, Bordeaux
Assistance Publique Hopitaux De Paris
Ophtalmology, 78 Rue Du General Leclerc, 94270, Le Kremlin-Bicetre
Hospices Civils De Lyon
Ophtalmology, 5 Place D Arsonval, 69437, Lyon Cedex 03
Centre Hospitalier Regional Et Universitaire De Brest
Ophtalmology, 2 Avenue Marechal Foch, 29200, Brest
Fondation A De Rothschild
Ophtalmology, 29 Rue Manin, 75019, Paris
Assistance Publique Hopitaux De Paris
Ophtalmology, 27 Rue Du Faubourg Saint Jacques, 75014, Paris
Centre Hospitalier Universitaire De Dijon
Ophtalmology, 14 Rue Paul Gaffarel, 21000, Dijon
Centre Hospitalier Universitaire De Saint Etienne
Ophtalmology, Avenue Albert Raimond, 42270, Saint Priest En Jarez
Centre Hospitalier Regional Universitaire De Tours
Ophtalmology, 2 Boulevard Tonnelle, 37000, Tours
Les Hopitaux Universitaires De Strasbourg
Ophtalmology, 1 Place De L Hopital, Cs 80426, Strasbourg Cedex

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) D1_Protocol_2023-509713-37-00 1.2
Protocol (for publication) D1_Protocol_2023-509713-37-00_Modifications-apparentes 1.2
Protocol (for publication) D1_Protocol_2023-509713-37-00_Redacted 1.2
Recruitment arrangements (for publication) K1_Recruitment arrangements_French_2023-509713-37-00 1
Subject information and informed consent form (for publication) L1_SIS and ICF adults 1.3
Subject information and informed consent form (for publication) L1_SIS and ICF adults version_Modifications-apparentes 1.3
Subject information and informed consent form (for publication) L1_SIS and ICF adults_Redacted 1.3
Synopsis of the protocol (for publication) D1_Protocol-synopsis_France_2023-509713-37-00 1.2
Synopsis of the protocol (for publication) D1_Protocol-synopsis_France_2023-509713-37-00_Modifications-apparentes 1.2
Synopsis of the protocol (for publication) D1_Protocol-synopsis_France_2023-509713-37-00_Redacted 1.2

Application history

1 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2025-07-31 France Acceptable
2025-12-07
 2025-12-09

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