Clinical trial NCT02126020: Topical Infliximab in Autoimmune Eyes With Keratoprosthesis
Official title: Topical Infliximab in Autoimmune Eyes With Keratoprosthesis
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Stevens-Johnson Syndrome
Toxic Epidermal Necrolysis (Lyell) Syndrome
Mucous Membrane Pemphigoid
Keywords: Keratoprosthesis
corneal melt
keratolysis
Tumor necrosis factor alpha
infliximab
matrix metalloproteinase
Lead sponsor: Massachusetts Eye and Ear Infirmary
Sponsor class: OTHER
Collaborators: name: Massachusetts Eye and Ear Infirmary
name: Fonds de recherche en ophtalmologie de l'Université de Montréal
First posted: 2014-04-29
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Tolerability
timeFrame: 1 year
measure: Adverse events
timeFrame: 2 years
measure: rate of corneal melting
timeFrame: 2 years
measure: KPro retention
timeFrame: 2 years
Secondary outcomes:
measure: Visual acuity
timeFrame: 2 years
measure: Ocular surface symptoms
timeFrame: 2 years
measure: Ocular surface inflammation
timeFrame: 2 years
measure: tear matrix metalloproteinase (MMP)
timeFrame: 2 years
measure: graft thickness
timeFrame: 2 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts Eye and Ear Infirmary
state: Massachusetts
city: Montréal
country: Canada
facility: Centre Hospitalier de l'Université de Montréal
state: Quebec
Study officials:
affiliation: Massachusetts Eye and Ear Infirmary
name: James Chodosh, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Massachusetts Eye and Ear Infirmary
name: Claes H Dohlman, MD, PhD
role: STUDY_CHAIR
affiliation: Centre hospitalier de l'Université de Montréal (CHUM)
name: Mona Harissi-Dagher, MD
role: STUDY_CHAIR
References: