Back to resultsTopical Infliximab in Autoimmune Eyes With Keratoprosthesis
Primary Purpose
Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis (Lyell) Syndrome, Mucous Membrane Pemphigoid
Status
Withdrawn
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
topical infliximab
Sponsored by
About this trial
This is an interventional prevention trial for Stevens-Johnson Syndrome focused on measuring Keratoprosthesis, corneal melt, keratolysis, Tumor necrosis factor alpha, infliximab, matrix metalloproteinase
Eligibility Criteria
Inclusion Criteria:
- Age between 18 and 80 years
- Able to provide informed consent
- Underlying diagnosis of SJS, TENS, or MMP
- Implantation of a Boston KPro type I
- Able to administer eye medications or have a care giver able and willing to do same
- Negative tuberculosis screening
Exclusion Criteria:
Active or recurrent ocular or systemic infection
- Chest radiography, QuantiFERON-TB Gold or purified protein derivative (PPD) evidence of active or latent tuberculosis infection
- Indeterminate initial and repeat QuantiFERON-TB Gold results
- History of Bacille Calmette-Guerin (BCG) vaccination within twelve months of screening
- History of latent or active granulomatous infection, including histoplasmosis or coccidioidomycosis, prior to screening
- Chest radiograph within three months prior to the first administration of the study drug that shows an abnormality suggestive of a malignancy or current active infection, including tuberculosis.
- History of a nontuberculous mycobacterial infection or opportunistic infection (e.g. cytomegalovirus, pneumocystosis, aspergillosis) within six months prior to screening
- history of hepatitis B virus
- Methicillin resistant Staphylococcus aureus (MRSA) or vancomycin resistant enterococcus (VRE) infection
- Malignancy diagnosed in the last five years
- Demyelinating disease
- History or current diagnosis of diabetes mellitus (controlled and uncontrolled)
- Heart failure (New York Heart Association class III or IV)
- Pregnancy or breast-feeding
- Scheduled to receive a live vaccine at any time point during study participation
- Allergy to infliximab or any of the compounds in its topical formulation or any chemically-related medication
- Prior or current use of systemic anti-tumor necrosis alpha-α medications or currently receiving treatments of Kineret (Anakinra)
- KPro designs with less than 16 holes in the back plate (to avoid the confounder of corneal nutrition)
- Inability to comply with the instillation of additional drops
- Unable to attend postoperative visits or administer medications, or no care giver available and willing to assist with same
Sites / Locations
- Massachusetts Eye and Ear Infirmary
- Centre Hospitalier de l'Université de Montréal
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
topical infliximab
Arm Description
topical infliximab 10 mg/mL QID x 3 months followed by BID x 9 months
Outcomes
Primary Outcome Measures
Tolerability
Percentage of patients finishing 12 months of topical infliximab use
Adverse events
Number and type of adverse events
rate of corneal melting
rate of corneal melting or ulceration during infliximab prophylaxis (12 months) and after the drug is stopped (following 12 months)
KPro retention
Percentage of retained KPros at 2 years
Secondary Outcome Measures
Visual acuity
Ocular surface symptoms
Ocular surface symptoms as assessed by ocular surface disease index score
Ocular surface inflammation
Ocular surface inflammation using slit-lamp photographs and the ocular redness index (ORI)
tear matrix metalloproteinase (MMP)
Levels and activity of MMPs, myeloperoxidase and tissue inhibitor of MMP-1
graft thickness
Corneal carrier graft thickness as measured by anterior segment optical coherence tomography before, during and after treatment with infliximab
Full Information
NCT ID
NCT02126020
First Posted
April 27, 2014
Last Updated
April 5, 2017
Sponsor
James Chodosh, MD, MPH
Collaborators
Massachusetts Eye and Ear Infirmary, Fonds de recherche en ophtalmologie de l'Université de Montréal
1. Study Identification
Unique Protocol Identification Number
NCT02126020
Brief Title
Topical Infliximab in Autoimmune Eyes With Keratoprosthesis
Official Title
Topical Infliximab in Autoimmune Eyes With Keratoprosthesis
Study Type
Interventional
2. Study Status
Record Verification Date
April 2017
Overall Recruitment Status
Withdrawn
Why Stopped
No patients met eligibility criteria. The study has been closed.
Study Start Date
November 2014 (undefined)
Primary Completion Date
April 3, 2017 (Actual)
Study Completion Date
April 3, 2017 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
James Chodosh, MD, MPH
Collaborators
Massachusetts Eye and Ear Infirmary, Fonds de recherche en ophtalmologie de l'Université de Montréal
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The Boston Keratoprosthesis type I (KPro) is a prosthetic cornea used to treat several causes of corneal blindness. Some categories of patients, including those with auto-immune diseases such as Stevens-Johnson syndrome, toxic epidermal necrolysis syndrome and mucous membrane pemphigoid, have a higher risk of failure for the KPro. Because of chronic inflammation, the cornea supporting the KPro may melt, leading to a higher risk of infection, loss of the KPro and loss of the eye.
Infliximab is an antibody against tumor necrosis factor alpha and is used intravenously to control inflammation in several diseases. It has been used in some cases of corneal melting with significant success.
This study's hypothesis is that infliximab can be successfully used as an eye drop (instead of the usual administration through veins) and that its regular use may prevent melt in eyes with a Boston Keratoprosthesis type I and underlying auto-immune disease.
Detailed Description
This is an unmasked, prospective, multicenter clinical trial of four patients that are candidates for a Boston Keratoprosthesis or have had prior KPro surgery and have a diagnosis of Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis syndrome (TENS) or mucous membrane pemphigoid (MMP). Only one eye per patient will be considered for inclusion.
This is a phase I/II study to evaluate the safety and tolerance of topical infliximab 10 mg/mL eye drops. Research subjects will be required to administer infliximab eye drops four times per day for three months followed by twice daily administration for nine months. The subjects will be monitored while on the study medication as well as for one year following discontinuation of the drug. The total study duration for each patient will be two years.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis (Lyell) Syndrome, Mucous Membrane Pemphigoid
Keywords
Keratoprosthesis, corneal melt, keratolysis, Tumor necrosis factor alpha, infliximab, matrix metalloproteinase
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
topical infliximab
Arm Type
Experimental
Arm Description
topical infliximab 10 mg/mL QID x 3 months followed by BID x 9 months
Intervention Type
Drug
Intervention Name(s)
topical infliximab
Other Intervention Name(s)
Remicade
Intervention Description
topical infliximab administered QID for 3 months followed by BID for 9 months
Primary Outcome Measure Information:
Title
Tolerability
Description
Percentage of patients finishing 12 months of topical infliximab use
Time Frame
1 year
Title
Adverse events
Description
Number and type of adverse events
Time Frame
2 years
Title
rate of corneal melting
Description
rate of corneal melting or ulceration during infliximab prophylaxis (12 months) and after the drug is stopped (following 12 months)
Time Frame
2 years
Title
KPro retention
Description
Percentage of retained KPros at 2 years
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Visual acuity
Time Frame
2 years
Title
Ocular surface symptoms
Description
Ocular surface symptoms as assessed by ocular surface disease index score
Time Frame
2 years
Title
Ocular surface inflammation
Description
Ocular surface inflammation using slit-lamp photographs and the ocular redness index (ORI)
Time Frame
2 years
Title
tear matrix metalloproteinase (MMP)
Description
Levels and activity of MMPs, myeloperoxidase and tissue inhibitor of MMP-1
Time Frame
2 years
Title
graft thickness
Description
Corneal carrier graft thickness as measured by anterior segment optical coherence tomography before, during and after treatment with infliximab
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age between 18 and 80 years
Able to provide informed consent
Underlying diagnosis of SJS, TENS, or MMP
Implantation of a Boston KPro type I
Able to administer eye medications or have a care giver able and willing to do same
Negative tuberculosis screening
Exclusion Criteria:
Active or recurrent ocular or systemic infection
Chest radiography, QuantiFERON-TB Gold or purified protein derivative (PPD) evidence of active or latent tuberculosis infection
Indeterminate initial and repeat QuantiFERON-TB Gold results
History of Bacille Calmette-Guerin (BCG) vaccination within twelve months of screening
History of latent or active granulomatous infection, including histoplasmosis or coccidioidomycosis, prior to screening
Chest radiograph within three months prior to the first administration of the study drug that shows an abnormality suggestive of a malignancy or current active infection, including tuberculosis.
History of a nontuberculous mycobacterial infection or opportunistic infection (e.g. cytomegalovirus, pneumocystosis, aspergillosis) within six months prior to screening
history of hepatitis B virus
Methicillin resistant Staphylococcus aureus (MRSA) or vancomycin resistant enterococcus (VRE) infection
Malignancy diagnosed in the last five years
Demyelinating disease
History or current diagnosis of diabetes mellitus (controlled and uncontrolled)
Heart failure (New York Heart Association class III or IV)
Pregnancy or breast-feeding
Scheduled to receive a live vaccine at any time point during study participation
Allergy to infliximab or any of the compounds in its topical formulation or any chemically-related medication
Prior or current use of systemic anti-tumor necrosis alpha-α medications or currently receiving treatments of Kineret (Anakinra)
KPro designs with less than 16 holes in the back plate (to avoid the confounder of corneal nutrition)
Inability to comply with the instillation of additional drops
Unable to attend postoperative visits or administer medications, or no care giver available and willing to assist with same
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
James Chodosh, MD, MPH
Organizational Affiliation
Massachusetts Eye and Ear Infirmary
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Claes H Dohlman, MD, PhD
Organizational Affiliation
Massachusetts Eye and Ear Infirmary
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Mona Harissi-Dagher, MD
Organizational Affiliation
Centre hospitalier de l'Université de Montréal (CHUM)
Official's Role
Study Chair
Facility Information:
Facility Name
Massachusetts Eye and Ear Infirmary
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Centre Hospitalier de l'Université de Montréal
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H2L 4M1
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
No
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Topical Infliximab in Autoimmune Eyes With Keratoprosthesis
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