Infliximab to Improve Retention of the Boston Keratoprosthesis in Patients After Stevens Johnson Syndrome/ Toxic Epidermal Necrolysis (SJS/TENS)

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2012 by Massachusetts Eye and Ear Infirmary
Sponsor:
Information provided by (Responsible Party):
Massachusetts Eye and Ear Infirmary
ClinicalTrials.gov Identifier:
NCT01256489
First received: November 19, 2010
Last updated: December 18, 2012
Last verified: December 2012
  Purpose

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.


Condition Intervention Phase
Stevens-Johnson Syndrome
Corneal Blindness
Drug: Infliximab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Infliximab Therapy to Improve Retention of the Boston Keratoprosthesis in Patients After Stevens Johnson Syndrome/ Toxic Epidermal Necrolysis

Resource links provided by NLM:


Further study details as provided by Massachusetts Eye and Ear Infirmary:

Primary Outcome Measures:
  • Occurrence of corneal ulceration [ Time Frame: Assessed monthly for up to 2 years following surgery ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Occurrence of systemic adverse events [ Time Frame: Assessed monthly for up to 2 years following first infusion ] [ Designated as safety issue: Yes ]
  • Period Of Prosthesis Retention [ Time Frame: Assessed monthly for up to 2 years following surgery ] [ Designated as safety issue: No ]
  • Vision Recovery [ Time Frame: Assessed monthly for up to 2 years following surgery ] [ Designated as safety issue: No ]

Estimated Enrollment: 4
Study Start Date: December 2010
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Infliximab
Every patient enrolled in the study will receive monthly infusions of Infliximab throughout the term of the study. Infliximab will be administered intravenously.
Drug: Infliximab
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.
Other Name: Remicade

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01256489

Contacts
Contact: Nicholas Simms 617-573-3173 Nicholas_Simms@meei.harvard.edu

Locations
United States, Massachusetts
Massachusetts Eye and Ear Infirmary Recruiting
Boston, Massachusetts, United States, 02114
Contact: Cornea Research Office    617-573-3313    cornea_research@meei.harvard.edu   
Contact: Nicholas Simms    617-573-3173    Nicholas_Simms@meei.harvard.edu   
Principal Investigator: James Chodosh, MD, MPH         
Sponsors and Collaborators
Massachusetts Eye and Ear Infirmary
Investigators
Principal Investigator: James Chodosh, MD, MPH Massachusetts Eye and Ear Infirmary
  More Information

No publications provided

Responsible Party: Massachusetts Eye and Ear Infirmary
ClinicalTrials.gov Identifier: NCT01256489     History of Changes
Other Study ID Numbers: 10-02-010, 196405
Study First Received: November 19, 2010
Last Updated: December 18, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Massachusetts Eye and Ear Infirmary:
KPro
Keratoprosthesis
Stevens-Johnson Syndrome
Infliximab
Corneal Blindness

Additional relevant MeSH terms:
Staphylococcal Skin Infections
Skin Diseases, Infectious
Staphylococcal Scalded Skin Syndrome
Stevens-Johnson Syndrome
Blindness
Staphylococcal Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Skin Diseases, Bacterial
Infection
Skin Diseases
Stomatitis
Mouth Diseases
Stomatognathic Diseases
Drug Eruptions
Dermatitis
Erythema Multiforme
Erythema
Skin Diseases, Vesiculobullous
Drug Hypersensitivity
Hypersensitivity
Immune System Diseases
Drug-Related Side Effects and Adverse Reactions
Chemically-Induced Disorders
Vision Disorders
Sensation Disorders
Neurologic Manifestations
Nervous System Diseases
Eye Diseases
Signs and Symptoms

ClinicalTrials.gov processed this record on August 21, 2014