Topical Infliximab in Autoimmune Eyes With Keratoprosthesis

Brief Title

Topical Infliximab in Autoimmune Eyes With Keratoprosthesis

Official Title

Topical Infliximab in Autoimmune Eyes With Keratoprosthesis

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.
    

Study Phase

Phase 1/Phase 2

Study Type

Interventional

Primary Outcome

Tolerability

Secondary Outcome

 Visual acuity

Condition

Stevens-Johnson Syndrome

Intervention

topical infliximab

Study Arms / Comparison Groups

 topical infliximab

Description:  topical infliximab 10 mg/mL QID x 3 months followed by BID x 9 months

Publications

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

Recruitment Status

Drug

Estimated Enrollment

0

Start Date

November 2014

Completion Date

April 3, 2017

Primary Completion Date

April 3, 2017

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
      

Gender

All

Ages

18 Years - 80 Years

Accepts Healthy Volunteers

No

Contacts

James Chodosh, MD, MPH, , 

Location Countries

Canada

Location Countries

Canada

NCT ID

NCT02126020

Organization ID

MEEI 13-110H

Secondary IDs

IND 122719

Responsible Party

Sponsor-Investigator

Study Sponsor

James Chodosh, MD, MPH

Collaborators

 Massachusetts Eye and Ear Infirmary

Study Sponsor

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

Verification Date

April 2017