Topical Infliximab in Autoimmune Eyes With Keratoprosthesis

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified April 2014 by Massachusetts Eye and Ear Infirmary
Sponsor:
Collaborators:
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 & Ear Infirmary
ClinicalTrials.gov Identifier:
NCT02126020
First received: April 27, 2014
Last updated: NA
Last verified: April 2014
History: No changes posted
  Purpose

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 Intervention Phase
Stevens-Johnson Syndrome
Toxic Epidermal Necrolysis (Lyell) Syndrome
Mucous Membrane Pemphigoid
Drug: topical 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: Prevention
Official Title: Topical Infliximab in Autoimmune Eyes With Keratoprosthesis

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Tolerability [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Percentage of patients finishing 12 months of topical infliximab use

  • Adverse events [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Number and type of adverse events

  • rate of corneal melting [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    rate of corneal melting or ulceration during infliximab prophylaxis (12 months) and after the drug is stopped (following 12 months)

  • KPro retention [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Percentage of retained KPros at 2 years


Secondary Outcome Measures:
  • Visual acuity [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Ocular surface symptoms [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Ocular surface symptoms as assessed by ocular surface disease index score

  • Ocular surface inflammation [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Ocular surface inflammation using slit-lamp photographs and the ocular redness index (ORI)

  • tear matrix metalloproteinase (MMP) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Levels and activity of MMPs, myeloperoxidase and tissue inhibitor of MMP-1

  • graft thickness [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Corneal carrier graft thickness as measured by anterior segment optical coherence tomography before, during and after treatment with infliximab


Estimated Enrollment: 4
Study Start Date: September 2014
Estimated Study Completion Date: March 2017
Estimated Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT02126020

Contacts
Contact: James Chodosh, MD, MPH 617-573-3938 james_chodosh@MEEI.harvard.edu
Contact: Marie-Claude Robert, MD 617-573-3938 marie-claude_robert@MEEI.harvard.edu

Locations
United States, Massachusetts
Massachusetts Eye and Ear Infirmary Not yet recruiting
Boston, Massachusetts, United States, 02114
Contact: James Chodosh, MD, MPH    617-573-3938    James_chodosh@meei.harvard.edu   
Contact: Claes H Dohlman, MD, PhD    617-573-3938    claes_dohlman@meei.harvard.edu   
Principal Investigator: James Chodosh, MD, MPH         
Sub-Investigator: Claes H Dohlman, MD, PhD         
Canada, Quebec
Centre Hospitalier de l'Université de Montréal Not yet recruiting
Montréal, Quebec, Canada, H2L 4M1
Contact: Mona Harissi-Dagher, MD    (514) 890-8000 ext 26354    monadagher@hotmail.com   
Principal Investigator: Mona Harissi-Dagher, MD         
Sponsors and Collaborators
James Chodosh, MD, MPH
Massachusetts Eye and Ear Infirmary
Fonds de recherche en ophtalmologie de l'Université de Montréal (FROUM)
Investigators
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
Study Chair: Marie-Claude Robert, MD Massachusetts Eye and Ear Infirmary
  More Information

No publications provided

Responsible Party: James Chodosh, MD, MPH, Associate Director of the Cornea and Refractive Surgery Service, Director of Boston Keratoprosthesis Clinical Programs, Massachusetts Eye & Ear Infirmary
ClinicalTrials.gov Identifier: NCT02126020     History of Changes
Other Study ID Numbers: MEEI 13-110H
Study First Received: April 27, 2014
Last Updated: April 27, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by Massachusetts Eye and Ear Infirmary:
Keratoprosthesis
corneal melt
keratolysis
Tumor necrosis factor alpha
infliximab
matrix metalloproteinase

Additional relevant MeSH terms:
Pemphigoid, Benign Mucous Membrane
Staphylococcal Scalded Skin Syndrome
Stevens-Johnson Syndrome
Syndrome
Bacterial Infections
Chemically-Induced Disorders
Conjunctival Diseases
Dermatitis
Disease
Drug Eruptions
Drug Hypersensitivity
Drug-Related Side Effects and Adverse Reactions
Erythema
Erythema Multiforme
Eye Diseases
Gram-Positive Bacterial Infections
Hypersensitivity
Immune System Diseases
Infection
Mouth Diseases
Pathologic Processes
Skin Diseases
Skin Diseases, Bacterial
Skin Diseases, Infectious
Skin Diseases, Vesiculobullous
Staphylococcal Infections
Staphylococcal Skin Infections
Stomatitis
Stomatognathic Diseases
Infliximab

ClinicalTrials.gov processed this record on October 23, 2014