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

Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud

Status and phase: Completed; Phase 2; Phase 1

Conditions: Sequelae of Previous Trophic Corneal Ulcers; Severe Trophic Corneal Ulcers Refractory to Conventional Treatment

Treatments: Drug: Anterior lamellar nanostructured artificial human cornea.; Other: Amniotic membrane transplantation

Study type: Interventional

Funder types: Other

Identifiers

NCT01765244

2010-024290-40 (EudraCT Number)

CAH/Ulc/2010

Details and patient eligibility

About

This is a prospective, phase I-II, randomised, open-label clinical trial that will evaluate the safety and feasibility, as well as clinical efficacy evidence, of a bioengineered anterior corneal substitute in adults with severe trophic corneal ulcers. This model of human anterior allogeneic cornea will provide an alternative approach in cases where human donor keratoplasty is not an option.

Full description

This is a phase I-II, randomised, controlled, open-label clinical trial, currently ongoing in eleven Spanish hospitals, to evaluate the safety and feasibility, as well as clinical efficacy evidence, of a bioengineered human anterior corneal substitute in adults with severe trophic corneal ulcers refractory to conventional treatment, or with sequelae of previous ulcers. In the initial phase of the trial (n=5), patients were sequentially recruited, with a safety period of 45 days, receiving the bioengineered corneal graft. In the second phase of the trial (currently ongoing), subjects are block randomised (2:1) to receive either the corneal graft (n=10), or amniotic membrane (n=5), as the control treatment. Adverse events, implant status, infection signs and induced neovascularization are evaluated as determinants of safety and feasibility of the bioengineered graft (main outcomes). Study endpoints are measured along a follow-up period of 24 months, including 27 post-implant assessment visits according to a decreasing frequency. Intention to treat, and per protocol, and safety analysis will be performed.

Enrollment: 16 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Man or woman aged≥18, with no upper age limit.
• Patients that give their informed consent for study participation.
• Stage 3 Mackie corneal ulcers that do not respond to conventional medical treatment, or patients having undergone previous stage 3 Mackie corneal ulcers,33 currently suffering sequelae such as stromal fibrosis or corneal thinning, having no effective therapeutic alternative.
• Stromal involvement, not reaching the Descemet membrane. Central or peripheral localization.
• Minimum duration of the disease causing the corneal ulcer: 6 weeks.
• No active ocular infection.
• Patients with normal laboratory parameters as defined by: Leukocytes≥3000 cells/µL; Neutrophils≥1500 cells/µL; Platelets≥100 billion/L; AST/ALT≤1.5 ULN; Creatinine≤1.5 mg/dL.

Exclusion criteria

• Absence of stromal involvement.
• Good response to standard medical treatments for corneal disease in less than 3 to 5 weeks.
• Bullous keratopathy or other endothelial decompensations.
• Active ocular infection.
• Positive serology to HBV, HCV, HIV or any other pathology that may interfere with correct patient follow-up.
• Pregnant or breast-feeding women or childbearing-age women that do not consent the use of contraceptive methods approved in the protocol.
• Medical history of active neoplasia within the past 5 years. Participation in other clinical trials in 3 months previous to inclusion, or in the previous 5 years for trials with advanced therapies.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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16 participants in 2 patient groups

Anterior lamellar nanostructured artificial human cornea

Experimental group

Description:

Anterior lamellar nanostructured artificial human cornea with allogenic from dead donor and cultured in its inside and allogeneic corneal epithelium cultured in its surface

Treatment:

Drug: Anterior lamellar nanostructured artificial human cornea.

Amniotic membrane transplantation

Active Comparator group

Description:

Amniotic membrane transplantation as conventional treatment of corneal trophic ulcers.

Treatment:

Other: Amniotic membrane transplantation