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

Primary Purpose

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

Status
Completed
Phase
Phase 1
Locations
Spain
Study Type
Interventional
Intervention
Anterior lamellar nanostructured artificial human cornea.
Amniotic membrane transplantation
Sponsored by
Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Severe Trophic Corneal Ulcers Refractory to Conventional Treatment focused on measuring Corneal trophic ulcers, limbal deficiency, cornea blindness

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • Hospital San Juan de Dios
  • University Hospital Puerta del Mar
  • Hospital la Arruzafa
  • Hospital Universitario Reina Sofía
  • University Hospital San Cecilio
  • University Hospital Virgen de las Nieves
  • Hospital Costa del Sol
  • Marina Rodriguez Calvo-Mora
  • University Hospital Virgen Macarena
  • University Hospital Virgen de Rocío
  • Hospital Nuestra Señora de Valme

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Anterior lamellar nanostructured artificial human cornea

Amniotic membrane transplantation

Arm 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

Amniotic membrane transplantation as conventional treatment of corneal trophic ulcers.

Outcomes

Primary Outcome Measures

Adverse events (and serious adverse events) causally related to experimental treatment.
Implant status (integrity, detachment and reabsorption)
Local, regional or systemic infections related with the implant
Induced corneal neovascularization

Secondary Outcome Measures

Ulcer persistency or relapse and corneal stromal repair
Visual acuity
Corneal transparency
Tear function (TBUT and Schirmer)
Quality of life (EQ-5)
Induced chronic ocular complications
In vivo confocal microscopy (IVCM) analysis of the grafted bioengineered cornea (and AM)

Full Information

First Posted
January 9, 2013
Last Updated
January 19, 2021
Sponsor
Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud
Collaborators
Iniciativa Andaluza en Terapias Avanzadas
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1. Study Identification

Unique Protocol Identification Number
NCT01765244
Brief Title
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

2. Study Status

Record Verification Date
January 2021
Overall Recruitment Status
Completed
Study Start Date
January 17, 2014 (Actual)
Primary Completion Date
January 14, 2021 (Actual)
Study Completion Date
January 14, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud
Collaborators
Iniciativa Andaluza en Terapias Avanzadas

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Severe Trophic Corneal Ulcers Refractory to Conventional Treatment, Sequelae of Previous Trophic Corneal Ulcers
Keywords
Corneal trophic ulcers, limbal deficiency, cornea blindness

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Bioengineered anterior human corneal substitute Amniotic membrane corneal graft
Masking
None (Open Label)
Allocation
Randomized
Enrollment
16 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Anterior lamellar nanostructured artificial human cornea
Arm Type
Experimental
Arm 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
Arm Title
Amniotic membrane transplantation
Arm Type
Active Comparator
Arm Description
Amniotic membrane transplantation as conventional treatment of corneal trophic ulcers.
Intervention Type
Drug
Intervention Name(s)
Anterior lamellar nanostructured artificial human cornea.
Other Intervention Name(s)
Bioengineered human anterior corneal substitute
Intervention Description
Implantation of an anterior lamellar nanostructured artificial human cornea with allogeneic cells from dead donors embedded in a fibrin-agarose scaffold
Intervention Type
Other
Intervention Name(s)
Amniotic membrane transplantation
Intervention Description
Implantation of an amniotic membrane graft to cover the corneal scarring using the mixed graft/patch technique.
Primary Outcome Measure Information:
Title
Adverse events (and serious adverse events) causally related to experimental treatment.
Time Frame
24 months
Title
Implant status (integrity, detachment and reabsorption)
Time Frame
24 months
Title
Local, regional or systemic infections related with the implant
Time Frame
24 months
Title
Induced corneal neovascularization
Time Frame
24 months
Secondary Outcome Measure Information:
Title
Ulcer persistency or relapse and corneal stromal repair
Time Frame
24 months
Title
Visual acuity
Time Frame
24 months
Title
Corneal transparency
Time Frame
24 months
Title
Tear function (TBUT and Schirmer)
Time Frame
24 months
Title
Quality of life (EQ-5)
Time Frame
24 months
Title
Induced chronic ocular complications
Time Frame
24 months
Title
In vivo confocal microscopy (IVCM) analysis of the grafted bioengineered cornea (and AM)
Time Frame
24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Santiago Medialdea, MD, PhD
Organizational Affiliation
Hospital U Virgen de las Nieves
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Miguel Alaminos, MD, PhD
Organizational Affiliation
Universidad de Granada
Official's Role
Study Chair
Facility Information:
Facility Name
Hospital San Juan de Dios
City
Bormujos
Country
Spain
Facility Name
University Hospital Puerta del Mar
City
Cádiz
ZIP/Postal Code
11009
Country
Spain
Facility Name
Hospital la Arruzafa
City
Córdoba
Country
Spain
Facility Name
Hospital Universitario Reina Sofía
City
Córdoba
Country
Spain
Facility Name
University Hospital San Cecilio
City
Granada
ZIP/Postal Code
18012
Country
Spain
Facility Name
University Hospital Virgen de las Nieves
City
Granada
ZIP/Postal Code
18014
Country
Spain
Facility Name
Hospital Costa del Sol
City
Marbella
Country
Spain
Facility Name
Marina Rodriguez Calvo-Mora
City
Málaga
Country
Spain
Facility Name
University Hospital Virgen Macarena
City
Sevilla
ZIP/Postal Code
41009
Country
Spain
Facility Name
University Hospital Virgen de Rocío
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Facility Name
Hospital Nuestra Señora de Valme
City
Sevilla
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
28947445
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.
Results Reference
background
Links:
URL
http://www.juntadeandalucia.es/terapiasavanzadas/
Description
Andalusian Initiative for Advanced Therapies

Learn more about this trial

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

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