Clinical trial NCT01765244: Allogeneic Tissue Engineering (Nanostructured Artificial Human Cornea) in Patients With Corneal Trophic Ulcers in Advanced Stages, Refractory to Conventional (Ophthalmic) Treatment
Official title: Multicenter Clinical Trial to Evaluate the Safety and Feasibility of an Allogeneic Tissue Engineered Drug (Nanostructured Artificial Human Cornea) in Patients With Corneal Trophic Ulcers Refractory to Conventional Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Severe Trophic Corneal Ulcers Refractory to Conventional Treatment
Sequelae of Previous Trophic Corneal Ulcers
Keywords: Corneal trophic ulcers, limbal deficiency, cornea blindness
Lead sponsor: Andalusian Network for Design and Translation of Advanced Therapies
Sponsor class: OTHER
Collaborators: name: Iniciativa Andaluza en Terapias Avanzadas
First posted: 2013-01-10
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Bioengineered anterior human corneal substitute Amniotic membrane corneal graft
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Adverse events (and serious adverse events) causally related to experimental treatment.
timeFrame: 24 months
measure: Implant status (integrity, detachment and reabsorption)
timeFrame: 24 months
measure: Local, regional or systemic infections related with the implant
timeFrame: 24 months
measure: Induced corneal neovascularization
timeFrame: 24 months
Secondary outcomes:
measure: Ulcer persistency or relapse and corneal stromal repair
timeFrame: 24 months
measure: Visual acuity
timeFrame: 24 months
measure: Corneal transparency
timeFrame: 24 months
measure: Tear function (TBUT and Schirmer)
timeFrame: 24 months
measure: Quality of life (EQ-5)
timeFrame: 24 months
measure: Induced chronic ocular complications
timeFrame: 24 months
measure: In vivo confocal microscopy (IVCM) analysis of the grafted bioengineered cornea (and AM)
timeFrame: 24 months
Other outcomes:
Locations:
city: Bormujos
country: Spain
facility: Hospital San Juan de Dios
city: Cádiz
country: Spain
facility: University Hospital Puerta del Mar
city: Córdoba
country: Spain
facility: Hospital la Arruzafa
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofía
city: Granada
country: Spain
facility: University Hospital San Cecilio
city: Granada
country: Spain
facility: University Hospital Virgen de las Nieves
city: Marbella
country: Spain
facility: Hospital Costa del Sol
city: Málaga
country: Spain
facility: Marina Rodriguez Calvo-Mora
city: Sevilla
country: Spain
facility: University Hospital Virgen Macarena
city: Sevilla
country: Spain
facility: University Hospital Virgen de Rocío
city: Sevilla
country: Spain
facility: Hospital Nuestra Señora de Valme
Study officials:
affiliation: Hospital U Virgen de las Nieves
name: Santiago Medialdea, MD, PhD
role: STUDY_DIRECTOR
affiliation: Universidad de Granada
name: Miguel Alaminos, MD, PhD
role: STUDY_CHAIR
References:
citation: 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.