Severe Trophic Corneal Ulcers Refractory to Conventional TreatmentPhase 1/2NCT01765244
Allogeneic Tissue Engineering (Nanostructured Artificial Human Cornea) in Patients With Corneal Trophic Ulcers in Advanced Stages, Refractory to Conventional (Ophthalmic) Treatment
A Phase 1/2 study testing Anterior lamellar nanostructured artificial human cornea. and Amniotic membrane transplantation in people with Severe Trophic Corneal Ulcers Refractory to Conventional Treatment and Sequelae of Previous Trophic Corneal Ulcers, run by Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud at 11 sites in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Severe Trophic Corneal Ulcers Refractory to Conventional Treatment, Sequelae of Previous Trophic Corneal Ulcers
- What is being tested?
- Anterior lamellar nanostructured artificial human cornea. and Amniotic membrane transplantation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 11 sitesSpain
- Study dates
- 17 Jan 2014to 14 Jan 2021
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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 locations and contacts
11 sites in 1 country.
11 sites in 1 country
Spain11 sites
Hospital San Juan de Dios
Bormujos
University Hospital Puerta del Mar
Cadiz, 11009
Hospital la Arruzafa
Córdoba
Hospital Universitario Reina Sofía
Córdoba
University Hospital San Cecilio
Granada, 18012
University Hospital Virgen de las Nieves
Granada, 18014
Marina Rodriguez Calvo-Mora
Málaga
Hospital Costa del Sol
Marbella
University Hospital Virgen Macarena
Seville, 41009
University Hospital Virgen de Rocío
Seville, 41013
Hospital Nuestra Señora de Valme
Seville
About this study
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
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.
Read the 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
- Being tested
- Anterior lamellar nanostructured artificial human cornea., Amniotic membrane transplantation
- Keywords
- Corneal trophic ulcers, limbal deficiency, cornea blindness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anterior lamellar nanostructured artificial human cornea.Drug
Also called Bioengineered human anterior corneal substitute
Implantation of an anterior lamellar nanostructured artificial human cornea with allogeneic cells from dead donors embedded in a fibrin-agarose scaffold
Amniotic membrane transplantationOther
Implantation of an amniotic membrane graft to cover the corneal scarring using the mixed graft/patch technique.
| Study group | Role | What they receive |
|---|---|---|
| Anterior lamellar nanostructured artificial human cornea | Experimental | Anterior lamellar nanostructured artificial human cornea with allogenic from dead donor and cultured in its inside and allogeneic corneal epithelium cultured in its surface Receives: Drug: Anterior lamellar nanostructured artificial human cornea. |
| Amniotic membrane transplantation | Active comparator | Amniotic membrane transplantation as conventional treatment of corneal trophic ulcers. Receives: Other: Amniotic membrane transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events (and serious adverse events) causally related to experimental treatment.
Measured: 24 months
Implant status (integrity, detachment and reabsorption)
Measured: 24 months
Local, regional or systemic infections related with the implant
Measured: 24 months
Induced corneal neovascularization
Measured: 24 months
Secondary outcomes (7)
Ulcer persistency or relapse and corneal stromal repair
Measured: 24 months
Visual acuity
Measured: 24 months
Corneal transparency
Measured: 24 months
Tear function (TBUT and Schirmer)
Measured: 24 months
Quality of life (EQ-5)
Measured: 24 months
Induced chronic ocular complications
Measured: 24 months
In vivo confocal microscopy (IVCM) analysis of the grafted bioengineered cornea (and AM)
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jan 2013 (estimated)
- Study start17 Jan 2014
- Primary completion14 Jan 2021
- Study completion14 Jan 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Severe Trophic Corneal Ulcers Refractory to Conventional TreatmentStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Bioengineered anterior human corneal substitute Amniotic membrane corneal graft
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud
- Sponsor type
- University, hospital or other
- Collaborators
- Iniciativa Andaluza en Terapias Avanzadas
- Responsible party
- Sponsor
- Investigators
- Santiago Medialdea, MD, PhD, Study director, Hospital U Virgen de las NievesMiguel Alaminos, MD, PhD, Study chair, Universidad de Granada
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01765244
- Sponsor's protocol ID
- CAH/Ulc/2010
- Other IDs
- 2010-024290-40
- Status last verified
- Jan 2021
- First submitted
- 9 Jan 2013
- Last updated
- 20 Jan 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 28947445
Study at a glance
From the registry record, last updated by the sponsor on 20 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01765244
- Acronym / sponsor ID
- CAH/Ulc/2010
- Conditions
- Severe Trophic Corneal Ulcers Refractory to Conventional Treatment, Sequelae of Previous Trophic Corneal Ulcers
- Keywords
- Corneal trophic ulcers, limbal deficiency, cornea blindness
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y SaludUniversity, hospital or other
- Collaborators
- Iniciativa Andaluza en Terapias Avanzadas
- Study start
- 17 Jan 2014 (actual)
- Primary completion
- 14 Jan 2021 (actual)
- Study completion
- 14 Jan 2021 (actual)
- First posted
- 10 Jan 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Bioengineered anterior human corneal substitute Amniotic membrane corneal graft
| Arm | Type | Receives |
|---|---|---|
| Anterior lamellar nanostructured artificial human cornea | Experimental | Drug: 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 |
| Amniotic membrane transplantation | Active comparator | Other: Amniotic membrane transplantationAmniotic membrane transplantation as conventional treatment of corneal trophic ulcers. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Anterior lamellar nanostructured artificial human cornea.Also: Bioengineered human anterior corneal substituteImplantation of an anterior lamellar nanostructured artificial human cornea with allogeneic cells from dead donors embedded in a fibrin-agarose scaffold | Drug | Anterior lamellar nanostructured artificial human cornea |
| Amniotic membrane transplantationImplantation of an amniotic membrane graft to cover the corneal scarring using the mixed graft/patch technique. | Other | Amniotic membrane transplantation |
Primary outcome
Adverse events (and serious adverse events) causally related to experimental treatment.
Time frame: 24 months
Implant status (integrity, detachment and reabsorption)
Time frame: 24 months
Local, regional or systemic infections related with the implant
Time frame: 24 months
Induced corneal neovascularization
Time frame: 24 months
7 secondary outcomes
Ulcer persistency or relapse and corneal stromal repair
Time frame: 24 months
Visual acuity
Time frame: 24 months
Corneal transparency
Time frame: 24 months
Tear function (TBUT and Schirmer)
Time frame: 24 months
Quality of life (EQ-5)
Time frame: 24 months
Induced chronic ocular complications
Time frame: 24 months
In vivo confocal microscopy (IVCM) analysis of the grafted bioengineered cornea (and AM)
Time frame: 24 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jan 2021.
- Background: PubMed 28947445Gonzalez-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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Santiago Medialdea, MD, PhD study director
Hospital U Virgen de las Nieves
Miguel Alaminos, MD, PhD study chair
Universidad de Granada
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Anterior lamellar nanostructured artificial human cornea. and Amniotic membrane transplantation in people with Severe Trophic Corneal Ulcers Refractory to Conventional Treatment and Sequelae of Previous Trophic Corneal Ulcers, run by Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud at 11 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse events (and serious adverse events) causally related to experimental treatment. (time frame: 24 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01765244, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jan 2021.