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Topical Infliximab in Autoimmune Eyes With Keratoprosthesis

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ClinicalTrials.gov Identifier: NCT02126020
Recruitment Status : Withdrawn (No patients met eligibility criteria. The study has been closed.)
First Posted : April 29, 2014
Last Update Posted : April 7, 2017
Massachusetts Eye and Ear Infirmary
Fonds de recherche en ophtalmologie de l'Université de Montréal (FROUM)
Information provided by (Responsible Party):
James Chodosh, MD, MPH, Massachusetts Eye and Ear Infirmary

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.

Condition or disease Intervention/treatment Phase
Stevens-Johnson Syndrome Toxic Epidermal Necrolysis (Lyell) Syndrome Mucous Membrane Pemphigoid Drug: topical infliximab Phase 1 Phase 2

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 Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Topical Infliximab in Autoimmune Eyes With Keratoprosthesis
Study Start Date : November 2014
Primary Completion Date : April 3, 2017
Estimated Study Completion Date : April 3, 2017

Arm Intervention/treatment
Experimental: topical infliximab
topical infliximab 10 mg/mL QID x 3 months followed by BID x 9 months
Drug: topical infliximab
topical infliximab administered QID for 3 months followed by BID for 9 months
Other Name: Remicade

Primary Outcome Measures :
  1. Tolerability [ Time Frame: 1 year ]
    Percentage of patients finishing 12 months of topical infliximab use

  2. Adverse events [ Time Frame: 2 years ]
    Number and type of adverse events

  3. rate of corneal melting [ Time Frame: 2 years ]
    rate of corneal melting or ulceration during infliximab prophylaxis (12 months) and after the drug is stopped (following 12 months)

  4. KPro retention [ Time Frame: 2 years ]
    Percentage of retained KPros at 2 years

Secondary Outcome Measures :
  1. Visual acuity [ Time Frame: 2 years ]
  2. Ocular surface symptoms [ Time Frame: 2 years ]
    Ocular surface symptoms as assessed by ocular surface disease index score

  3. Ocular surface inflammation [ Time Frame: 2 years ]
    Ocular surface inflammation using slit-lamp photographs and the ocular redness index (ORI)

  4. tear matrix metalloproteinase (MMP) [ Time Frame: 2 years ]
    Levels and activity of MMPs, myeloperoxidase and tissue inhibitor of MMP-1

  5. graft thickness [ Time Frame: 2 years ]
    Corneal carrier graft thickness as measured by anterior segment optical coherence tomography before, during and after treatment with infliximab

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02126020

United States, Massachusetts
Massachusetts Eye and Ear Infirmary
Boston, Massachusetts, United States, 02114
Canada, Quebec
Centre Hospitalier de l'Université de Montréal
Montréal, Quebec, Canada, H2L 4M1
Sponsors and Collaborators
James Chodosh, MD, MPH
Massachusetts Eye and Ear Infirmary
Fonds de recherche en ophtalmologie de l'Université de Montréal (FROUM)
Principal Investigator: James Chodosh, MD, MPH Massachusetts Eye and Ear Infirmary
Study Chair: Claes H Dohlman, MD, PhD Massachusetts Eye and Ear Infirmary
Study Chair: Mona Harissi-Dagher, MD Centre hospitalier de l'Université de Montréal (CHUM)

Responsible Party: James Chodosh, MD, MPH, Associate Director of the Cornea and Refractive Surgery Service, Director of Boston Keratoprosthesis Clinical Programs, Massachusetts Eye and Ear Infirmary
ClinicalTrials.gov Identifier: NCT02126020     History of Changes
Other Study ID Numbers: MEEI 13-110H
IND 122719 ( Other Identifier: FDA )
First Posted: April 29, 2014    Key Record Dates
Last Update Posted: April 7, 2017
Last Verified: April 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by James Chodosh, MD, MPH, Massachusetts Eye and Ear Infirmary:
corneal melt
Tumor necrosis factor alpha
matrix metalloproteinase

Additional relevant MeSH terms:
Pemphigoid, Bullous
Stevens-Johnson Syndrome
Pemphigoid, Benign Mucous Membrane
Pathologic Processes
Skin Diseases, Vesiculobullous
Skin Diseases
Autoimmune Diseases
Immune System Diseases
Mouth Diseases
Stomatognathic Diseases
Drug Eruptions
Erythema Multiforme
Drug Hypersensitivity
Drug-Related Side Effects and Adverse Reactions
Chemically-Induced Disorders
Conjunctival Diseases
Eye Diseases
Dermatologic Agents
Gastrointestinal Agents
Antirheumatic Agents