Stevens-Johnson SyndromePhase 1/2NCT01256489
Infliximab to Improve Retention of the Boston Keratoprosthesis in Patients After Stevens Johnson Syndrome/ Toxic Epidermal Necrolysis (SJS/TENS)
A Phase 1/2 study testing Infliximab in people with Stevens-Johnson Syndrome and Corneal Blindness, run by Massachusetts Eye and Ear Infirmary at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stevens-Johnson Syndrome, Corneal Blindness
- What is being tested?
- Infliximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2010to Jan 2015
- 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
- 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
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- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts Eye and Ear Infirmary
Boston, Massachusetts, 02114
About this study
Official title: Infliximab Therapy to Improve Retention of the Boston Keratoprosthesis in Patients After Stevens Johnson Syndrome/ Toxic Epidermal Necrolysis
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.
Read the 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.
- Conditions
- Stevens-Johnson Syndrome, Corneal Blindness
- Being tested
- Infliximab
- Keywords
- KPro, Keratoprosthesis, Stevens-Johnson Syndrome, Infliximab, Corneal Blindness
- Medical subject headings
- Stevens-Johnson Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
InfliximabDrug
Also called Remicade
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.
| Study group | Role | What they receive |
|---|---|---|
| Infliximab | Other | Every patient enrolled in the study will receive monthly infusions of Infliximab throughout the term of the study. Infliximab will be administered intravenously. Receives: Drug: Infliximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurrence of corneal ulceration
Measured: Assessed monthly for up to 2 years following surgery
Secondary outcomes (3)
Occurrence of systemic adverse events
Measured: Assessed monthly for up to 2 years following first infusion
Period Of Prosthesis Retention
Measured: Assessed monthly for up to 2 years following surgery
Vision Recovery
Measured: Assessed monthly for up to 2 years following surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2010 (estimated)
- Study startDec 2010
- Primary completionJan 2015
- Study completionJan 2015
Why it stopped: Steven Johnson's Syndrome (SJS) and Toxic Epidermal Necrolysis Syndrome (TENS) are rare (\~3 in 1 million). No eligible subjects have been identified.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Stevens-Johnson SyndromeStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts Eye and Ear Infirmary
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- James Chodosh, MD, MPH, Principal investigator, Massachusetts Eye and Ear Infirmary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01256489
- Sponsor's protocol ID
- 10-02-010
- Other IDs
- 196405
- Status last verified
- Jan 2015
- First submitted
- 19 Nov 2010
- Last updated
- 4 Nov 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Infliximab Therapy to Improve Retention of the Boston Keratoprosthesis in Patients After Stevens Johnson Syndrome/ Toxic Epidermal Necrolysis
- ClinicalTrials.gov ID
- NCT01256489
- Acronym / sponsor ID
- 10-02-010
- Conditions
- Stevens-Johnson Syndrome, Corneal Blindness
- Keywords
- KPro, Keratoprosthesis, Stevens-Johnson Syndrome, Infliximab, Corneal Blindness
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Steven Johnson's Syndrome (SJS) and Toxic Epidermal Necrolysis Syndrome (TENS) are rare (\~3 in 1 million). No eligible subjects have been identified.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Massachusetts Eye and Ear InfirmaryUniversity, hospital or other
- Study start
- Dec 2010
- Primary completion
- Jan 2015 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 8 Dec 2010 (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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Infliximab | Other | Drug: InfliximabEvery patient enrolled in the study will receive monthly infusions of Infliximab throughout the term of the study. Infliximab will be administered intravenously. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (21 listed)
- 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.
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 |
|---|---|---|
| InfliximabAlso: RemicadeThe 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. | Drug | Infliximab |
Primary outcome
Occurrence of corneal ulceration
Time frame: Assessed monthly for up to 2 years following surgery
3 secondary outcomes
Occurrence of systemic adverse events
Time frame: Assessed monthly for up to 2 years following first infusion
Period Of Prosthesis Retention
Time frame: Assessed monthly for up to 2 years following surgery
Vision Recovery
Time frame: Assessed monthly for up to 2 years following surgery
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2015.
Related trials for Stevens-Johnson Syndrome
Active, not recruitingPhase 2
Autologous Serum Obtained by a Closed-Circuit Collection Device
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Subconjunctival Humira for Boston Keratoprosthesis
Penetrating Keratoplasty, Multiple Graft Failure
Not yet recruitingPhase 4
HLA-B*58:01-Guided Therapy for Gout: Effectiveness, Safety, and Cost-Effectiveness
Gout Initiating Urate-loweringUrate-lowering Therapy, Gout Arthritis
Not yet recruitingPhase 1/2
New Therapeutic Target for Toxic Epidermal Necrolysis (TEN) Using Anti-CD38+ Monoclonal Antibodies.
Toxic Epidermal Necrolysis, Immunotherapy
RecruitingPhase 1/2
LYell SYndrome MEsenchymal Stromal Cells Treatment
Epidermal Necrolysis, Lyell Syndrome
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.
James Chodosh, MD, MPH principal investigator
Massachusetts Eye and Ear Infirmary
1 site 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 Infliximab in people with Stevens-Johnson Syndrome and Corneal Blindness, run by Massachusetts Eye and Ear Infirmary at 1 site in United States.
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 12 inclusion and 21 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: withdrawn, as of the sponsor's last update on 4 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 was withdrawn before enrolling participants, so there are no results.
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?
Occurrence of corneal ulceration (time frame: Assessed monthly for up to 2 years following surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Nov 2015.