Back to resultsInfliximab to Improve Retention of the Boston Keratoprosthesis in Patients After Stevens Johnson Syndrome/ Toxic Epidermal Necrolysis (SJS/TENS)
Primary Purpose
Stevens-Johnson Syndrome, Corneal Blindness
Status
Withdrawn
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Infliximab
Sponsored by
About this trial
This is an interventional treatment trial for Stevens-Johnson Syndrome focused on measuring KPro, Keratoprosthesis, Stevens-Johnson Syndrome, Infliximab, Corneal Blindness
Eligibility Criteria
Inclusion Criteria:
- History of biopsy proven SJS/TENS with corneal opacity and neovascularization
- Bilateral legal blindness (<20/200 in better eye)
- 18 years of age or older
- Able to provide informed consent
- Sufficiently healthy to undergo infliximab infusions, surgery, and a vigorous postoperative follow-up course
- Able to administer eye medications or have a care giver able and willing to do same
Are considered eligible according to the following tuberculosis (TB) screening criteria:
- Have no history of latent or active TB prior to screening.
- Have no signs or symptoms suggestive of active TB upon medical history and/or physical examination.
- Have had no recent close contact with a person with active TB.
- Within 6 weeks prior to the first administration of study agent, have a negative QuantiFERON-TB Gold test result (see Attachment A). Indeterminate results should be handled as outlined in the Screening Visit Section. A negative tuberculin skin test is considered acceptable if the QuantiFERON- TB Gold test is not acceptable in that country.
- Have a chest radiograph (posterior-anterior view) taken within 3 months prior to the first administration of study agent and read by a qualified radiologist, with no evidence of current, active TB or old, inactive TB.
Exclusion Criteria:
- Visual acuity >20/200 in better eye
- Corneal blindness not due to effects of SJS/TENS
- Hypersensitivity to infliximab or chemically related medication
- Pregnant or lactating
- Have a history of latent or active granulomatous infection, including histoplasmosis or coccidioidomycosis, prior to screening. Refer to inclusion criteria for information regarding eligibility with a history of latent TB.
- Have had a Bacille Calmette-Guérin (BCG) vaccination within 12 months of screening.
- Have a chest radiograph within 3 months prior to the first administration of study agent that shows an abnormality suggestive of a malignancy or current active infection, including TB.
- Have had a nontuberculous mycobacterial infection or opportunistic infection (eg, cytomegalovirus, pneumocystosis, aspergillosis) within 6 months prior to screening.
- Have indeterminate initial and repeat QuantiFERON-TB Gold test results.
- History or current diagnosis of diabetes mellitus
- History of immune system problem other than Stevens Johnson Syndrome
- History of recurrent infections
- History or current diagnosis of cancer
- Active psoriasis
- History of heart failure
- History of hepatitis B virus
- MRSA or VRE infection
- Nervous system disorders such as multiple sclerosis or Guillain-Barre syndrome
- Scheduled to receive a live vaccine at any time point during study participation
- Currently receiving treatments of Kineret (Anakinra)
- 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
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
Infliximab
Arm Description
Every patient enrolled in the study will receive monthly infusions of Infliximab throughout the term of the study. Infliximab will be administered intravenously.
Outcomes
Primary Outcome Measures
Occurrence of corneal ulceration
Secondary Outcome Measures
Occurrence of systemic adverse events
Period Of Prosthesis Retention
Vision Recovery
Full Information
NCT ID
NCT01256489
First Posted
November 19, 2010
Last Updated
November 3, 2015
Sponsor
Massachusetts Eye and Ear Infirmary
1. Study Identification
Unique Protocol Identification Number
NCT01256489
Brief Title
Infliximab to Improve Retention of the Boston Keratoprosthesis in Patients After Stevens Johnson Syndrome/ Toxic Epidermal Necrolysis (SJS/TENS)
Official Title
Infliximab Therapy to Improve Retention of the Boston Keratoprosthesis in Patients After Stevens Johnson Syndrome/ Toxic Epidermal Necrolysis
Study Type
Interventional
2. Study Status
Record Verification Date
January 2015
Overall Recruitment Status
Withdrawn
Why Stopped
Steven Johnson's Syndrome (SJS) and Toxic Epidermal Necrolysis Syndrome (TENS) are rare (~3 in 1 million). No eligible subjects have been identified.
Study Start Date
December 2010 (undefined)
Primary Completion Date
January 2015 (Actual)
Study Completion Date
January 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Massachusetts Eye and Ear Infirmary
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The proposed study is intended to test the idea, based upon current knowledge of the biology and physiology of corneal ulceration in SJS/TENS patients who receive a keratoprosthesis, and on the known effects of infliximab on matrix metalloproteinases, that infliximab therapy for such patients may reduce the likelihood of corneal ulceration, and hence extend the period of prosthesis retention and vision recovery.
Detailed Description
The closely related disorders, Stevens Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis Syndrome (TENS), represent rare but severe hypersensitivity responses to a systemic medication, and cause severe sloughing of the skin and mucous membranes. Approximately half of affected patients experience ocular involvement, which can lead to corneal opacity and vascularization, and in some patients, blindness. Corneal transplantation (corneal allograft) is typically unsuccessful in SJS/TENS, because of chronic inflammation at the ocular surface, leading to corneal neovascularization and opacity, tissue melt, ulceration, and perforation.
The Boston keratoprosthesis, an artificial cornea developed at the Massachusetts Eye and Ear Infirmary (MEEI) over the last 40 years, is an FDA approved device for patients with corneal blindness not amenable to corneal transplantation, and has restored the sight of thousands of such patients, but in SJS/TENS patients remains associated with tissue melts (tissue ulceration), perforation, and ultimately in some, loss of the eye. K-Pro surgery is currently the best option for patients with SJS or TENS and corneal blindness, but these patients also have the worst prognosis after surgery. While the outcomes of these surgeries for patients with SJS or TENS have improved dramatically in the past ten years, they are still unsatisfactory. Remicade® has been used in a small group of patients with SJS or TENS undergoing K-Pro surgery, with one remarkable success. The purpose of this study is to explore this treatment more fully.
For a case report detailing the use of infliximab in one patient, see the following article: Dohlman JG, Foster CS, Dohlman CH. "Boston Keratoprosthesis in Stevens-Johnson Syndrome: A case of using infliximab to prevent tissue necrosis." Digital Journal of Ophthalmology. 2009, Volume 15, Number 1.
Recently developed biologics have dramatically improved functional outcomes and quality of life in patients with autoimmune diseases. One such agent, infliximab, acts by blocking TNF alpha, a protein associated with tissue melting in the cornea, and is increasingly being used for autoimmune eye conditions, in addition to its FDA approved indication for recalcitrant rheumatoid arthritis.
The proposed study will determine the feasibility of combining infliximab with keratoprosthesis surgery, and will closely monitor patients for episodes of corneal melting: the primary outcome of the study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stevens-Johnson Syndrome, Corneal Blindness
Keywords
KPro, Keratoprosthesis, Stevens-Johnson Syndrome, Infliximab, Corneal Blindness
7. Study Design
Primary Purpose
Treatment
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
Infliximab
Arm Type
Other
Arm Description
Every patient enrolled in the study will receive monthly infusions of Infliximab throughout the term of the study. Infliximab will be administered intravenously.
Intervention Type
Drug
Intervention Name(s)
Infliximab
Other Intervention Name(s)
Remicade
Intervention Description
The drug will be administered intravenously every month for 110 weeks (duration of the study). The initial dose of infliximab will be 5mg/kg of body weight. The dose may be adjusted up to a maximal dosing of 10mg/kg depending upon disease activity, as judged by the investigators.
Primary Outcome Measure Information:
Title
Occurrence of corneal ulceration
Time Frame
Assessed monthly for up to 2 years following surgery
Secondary Outcome Measure Information:
Title
Occurrence of systemic adverse events
Time Frame
Assessed monthly for up to 2 years following first infusion
Title
Period Of Prosthesis Retention
Time Frame
Assessed monthly for up to 2 years following surgery
Title
Vision Recovery
Time Frame
Assessed monthly for up to 2 years following surgery
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
History of biopsy proven SJS/TENS with corneal opacity and neovascularization
Bilateral legal blindness (<20/200 in better eye)
18 years of age or older
Able to provide informed consent
Sufficiently healthy to undergo infliximab infusions, surgery, and a vigorous postoperative follow-up course
Able to administer eye medications or have a care giver able and willing to do same
Are considered eligible according to the following tuberculosis (TB) screening criteria:
Have no history of latent or active TB prior to screening.
Have no signs or symptoms suggestive of active TB upon medical history and/or physical examination.
Have had no recent close contact with a person with active TB.
Within 6 weeks prior to the first administration of study agent, have a negative QuantiFERON-TB Gold test result (see Attachment A). Indeterminate results should be handled as outlined in the Screening Visit Section. A negative tuberculin skin test is considered acceptable if the QuantiFERON- TB Gold test is not acceptable in that country.
Have a chest radiograph (posterior-anterior view) taken within 3 months prior to the first administration of study agent and read by a qualified radiologist, with no evidence of current, active TB or old, inactive TB.
Exclusion Criteria:
Visual acuity >20/200 in better eye
Corneal blindness not due to effects of SJS/TENS
Hypersensitivity to infliximab or chemically related medication
Pregnant or lactating
Have a history of latent or active granulomatous infection, including histoplasmosis or coccidioidomycosis, prior to screening. Refer to inclusion criteria for information regarding eligibility with a history of latent TB.
Have had a Bacille Calmette-Guérin (BCG) vaccination within 12 months of screening.
Have a chest radiograph within 3 months prior to the first administration of study agent that shows an abnormality suggestive of a malignancy or current active infection, including TB.
Have had a nontuberculous mycobacterial infection or opportunistic infection (eg, cytomegalovirus, pneumocystosis, aspergillosis) within 6 months prior to screening.
Have indeterminate initial and repeat QuantiFERON-TB Gold test results.
History or current diagnosis of diabetes mellitus
History of immune system problem other than Stevens Johnson Syndrome
History of recurrent infections
History or current diagnosis of cancer
Active psoriasis
History of heart failure
History of hepatitis B virus
MRSA or VRE infection
Nervous system disorders such as multiple sclerosis or Guillain-Barre syndrome
Scheduled to receive a live vaccine at any time point during study participation
Currently receiving treatments of Kineret (Anakinra)
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
Facility Information:
Facility Name
Massachusetts Eye and Ear Infirmary
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Infliximab to Improve Retention of the Boston Keratoprosthesis in Patients After Stevens Johnson Syndrome/ Toxic Epidermal Necrolysis (SJS/TENS)
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