Allogeneic Tissue Engineering (Nanostructured Artificial Human Cornea) in Patients With Corneal Trophic Ulcers in Advanced Stages, Refractory to Conventional (Ophthalmic) Treatment.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Red Andaluza De Diseno Y Traslacion De Terapias Avanzadas Fundacion Publica Andaluza Progreso Y Salud

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11]

Trial duration

5 Jul 2024 → ongoing

Decision date (initial)

2024-07-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-515481-13-00

EudraCT number

2010-024290-40

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate the safety, feasibility and evidence of clinical efficacy of a model of human artificial nanostructured lamellar corneal, in patients with severe corneal disease for which there is currently no effective therapeutic.

Secondary objectives 3

1. Generate artificial corneas nanostructured lamellar human allogeneic, from cadaver donor origin from sclero-corneal limbus and biomaterials.
2. Implement the nanostructured artificial corneas human in a group of patients randomized to the experimental group, suffering from severe corneal disease.
3. To evaluate the biosafety of nanostructured artificial corneas human implanted in patients to rule out severe and unexpected adverse reactions.

Conditions and MedDRA coding

Corneal trophic ulcers refractory to conventional treatment or sequelae of previous ulcers (such as stromal thinning or fibrosis), associated or not with limbal insufficiency of the same eye.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Patients that give their informed consent for study participation.
2. Stage 3 Mackie corneal ulcers that do not respond to conventional medical treatment, and may also be secondary to any of the following causes: Riley-Day syndrome (familial dysautonomia), Goldenhar-Gorlin syndrome, Mobius syndrome, Corneal hypoesthesia family, Diabetes, Multiple sclerosis, Leprosy, Hypovitaminosis A, Autoimmune disorders, Acoustic neuroma, Meningioma, Neuralgia, Aneurysm, Stroke, Neoplasia, Herpes simplex, Herpes zoster, Caustication, Wound, inflammation, or wearing contact lenses, Cataract surgery or keratoplasty (aggression to ciliary nerves), Abuse of topical anesthetics, Toxicity of timolol, betaxolol, diclofenac sodium or sulfacetamide, Lattice or granular, Orbital neoplasia.
3. Patients having undergone previous stage 3 Mackie corneal ulcers, currently suffering sequelae such as stromal fibrosis or corneal thinning, having no effective therapeutic alternative.
4. Stromal involvement, not reaching the Descemet membrane. Central or peripheral localization.
5. No active ocular infection.
6. Man or woman aged ≥18, with no upper age limit.
7. Minimum duration of the disease causing the corneal ulcer: 6 weeks.
8. Patients with normal laboratory parameters as defined by: Leukocytes ≥ 3000, Neutrophils ≥ 1500, Platelets ≥ 100000, AST/ALT ≤ 1.5 ULN, Creatinine ≤ 1.5 mg/dL.

Exclusion criteria 8

1. Absence of stromal involvement.
2. Good response to standard medical treatments for corneal disease in less than 3 to 5 weeks.
3. Active ocular infection.
4. Bullous keratopathy or other endothelial decompensations.
5. Positive serology to HBV, HCV, HIV or any other pathology that may interfere with correct patient follow-up. In the case of HIV, it is understood that a positive serology implies a positive value in the anti-HIV antibody. In the case of HCV, a serology is considered positive when a positive value is obtained for the anti-HCV antibody. Finally, in the case of HBV, positive serology is interpreted as a positive HBV-antigen value or a positive viral load value (HBV-NAT). The inclusion of the subject will not be ruled out if a positive anti-HBVc core antibody is present and the anti-HBVs immunization levels are high enough to guarantee adequate protection of the patient (anti-HBVs > 100 IU/L).
6. Pregnant or breast-feeding women or childbearing-age women that do not consent the use of contraceptive methods approved in the protocol. Hormonal contraceptive methods that inhibit ovulation (combining estrogens with progestogens or progestogens only) for oral, transdermal, intravaginal, injectable or implantable administration, IUD, surgical sterilization or total abstinence are described as an effective contraceptive method.
7. Medical history of active neoplasia within the past 5 years.
8. Participation in other clinical trials in 3 months previous to inclusion, or in the previous 5 years for trials with advanced therapies.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Incidence of adverse events and severe adverse events related with the IMP.
2. Graft conditions (artificial cornea): integrity, graft survival or reabsorption.
3. Local, regional or systemic infection signs.
4. Induced corneal vascularization.

Secondary endpoints 5

1. Ulcer persistence or regeneration of corneal stroma.
2. Visual acuity.
3. Corneal transparency.
4. Quality of life (EQ5, part I and II).
5. Characterization of corneal surface (impression citology & OCT mapping).

Investigational products

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

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Red Andaluza De Diseno Y Traslacion De Terapias Avanzadas Fundacion Publica Andaluza Progreso Y Salud

Sponsor organisation

Red Andaluza De Diseno Y Traslacion De Terapias Avanzadas Fundacion Publica Andaluza Progreso Y Salud

Address

Edificio S-2, Calle Americo Vespucio Nº 15, Parque Cientifico Y Tecnologico Cartuja 93 Calle Americo Vespucio Nº 15 Parque Cientifico Y Tecnologico Cartuja 93

City

Sevilla

Postcode

41092

Country

Spain

Scientific contact point

Organisation

Red Andaluza De Diseno Y Traslacion De Terapias Avanzadas Fundacion Publica Andaluza Progreso Y Salud

Contact name

Gloria Carmona Sánchez

Public contact point

Organisation

Red Andaluza De Diseno Y Traslacion De Terapias Avanzadas Fundacion Publica Andaluza Progreso Y Salud

Contact name

Blanca Quijano Ruiz

Locations

1 EU/EEA country · 11 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 5 files

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

Application history

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