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

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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

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.
    

Study Phase

Phase 1/Phase 2

Study Type

Interventional


Primary Outcome

Occurrence of corneal ulceration

Secondary Outcome

 Occurrence of systemic adverse events

Condition

Stevens-Johnson Syndrome

Intervention

Infliximab

Study Arms / Comparison Groups

 Infliximab
Description:  Every patient enrolled in the study will receive monthly infusions of Infliximab throughout the term of the study. Infliximab will be administered intravenously.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

0

Start Date

December 2010

Completion Date

January 2015

Primary Completion Date

January 2015

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
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

James Chodosh, MD, MPH, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT01256489

Organization ID

10-02-010

Secondary IDs

196405

Responsible Party

Sponsor

Study Sponsor

Massachusetts Eye and Ear Infirmary


Study Sponsor

James Chodosh, MD, MPH, Principal Investigator, Massachusetts Eye and Ear Infirmary


Verification Date

January 2015