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

NCT ID: NCT01765244

Last Updated: 2021-01-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-17
• Study Completion Date: 2021-01-14

Brief Summary

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.

Detailed 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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Anterior lamellar nanostructured artificial human cornea

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

Group Type: EXPERIMENTAL

Anterior lamellar nanostructured artificial human cornea.

Intervention Type: DRUG

Implantation of an anterior lamellar nanostructured artificial human cornea with allogeneic cells from dead donors embedded in a fibrin-agarose scaffold

Amniotic membrane transplantation

Amniotic membrane transplantation as conventional treatment of corneal trophic ulcers.

Group Type: ACTIVE_COMPARATOR

Amniotic membrane transplantation

Intervention Type: OTHER

Implantation of an amniotic membrane graft to cover the corneal scarring using the mixed graft/patch technique.

Interventions

Anterior lamellar nanostructured artificial human cornea.

Implantation of an anterior lamellar nanostructured artificial human cornea with allogeneic cells from dead donors embedded in a fibrin-agarose scaffold

Intervention Type: DRUG

Amniotic membrane transplantation

Implantation of an amniotic membrane graft to cover the corneal scarring using the mixed graft/patch technique.

Intervention Type: OTHER

Other Intervention Names

Bioengineered human anterior corneal substitute

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Iniciativa Andaluza en Terapias Avanzadas

OTHER

Sponsor Role: collaborator

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

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Santiago Medialdea, MD, PhD

Role: STUDY_DIRECTOR

Hospital U Virgen de las Nieves

Miguel Alaminos, MD, PhD

Role: STUDY_CHAIR

Universidad de Granada

Locations

Hospital San Juan de Dios

Bormujos, , Spain

University Hospital Puerta del Mar

Cadiz, , Spain

Hospital la Arruzafa

Córdoba, , Spain

Hospital Universitario Reina Sofía

Córdoba, , Spain

University Hospital San Cecilio

Granada, , Spain

University Hospital Virgen de las Nieves

Granada, , Spain

Hospital Costa del Sol

Marbella, , Spain

Marina Rodriguez Calvo-Mora

Málaga, , Spain

University Hospital Virgen Macarena

Seville, , Spain

University Hospital Virgen de Rocío

Seville, , Spain

Hospital Nuestra Señora de Valme

Seville, , Spain

Countries

Spain

References

Gonzalez-Andrades M, Mata R, Gonzalez-Gallardo MDC, Medialdea S, Arias-Santiago S, Martinez-Atienza J, Ruiz-Garcia A, Perez-Fajardo L, Lizana-Moreno A, Garzon I, Campos A, Alaminos M, Carmona G, Cuende N. A study protocol for a multicentre randomised clinical trial evaluating the safety and feasibility of a bioengineered human allogeneic nanostructured anterior cornea in patients with advanced corneal trophic ulcers refractory to conventional treatment. BMJ Open. 2017 Sep 24;7(9):e016487. doi: 10.1136/bmjopen-2017-016487.

Reference Type: BACKGROUND

PMID: 28947445 (View on PubMed)

Other Identifiers

2010-024290-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CAH/Ulc/2010

Identifier Type: -

Identifier Source: org_study_id