Clinical trial NCT02987686: Topical Infliximab for Sterile Corneal Melt
Official title: Topical Infliximab for the Treatment of Sterile Corneal Melt
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Sterile Corneal Melt
Keywords: Topical Infliximab
Cornea
Keratolysis
Lead sponsor: Centre hospitalier de l'Université de Montréal (CHUM)
Sponsor class: OTHER
Collaborators: name: Fonds de recherche en ophtalmologie de l'Université de Montréal
First posted: 2016-12-09
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Corneal melt is a complication that could affect very ill eyes and lead to the thinning of the cornea (the clear window covering of the eyes). This thinning can lead to severe consequences such as the leakage of the liquid inside the eye (ocular perforation), or even blindness. Corneal melt can be caused by certain infections or as a sterile process. This project only includes patients with a sterile corneal melt (without an infection) caused by diseases such as rosacea, Sjogren's syndrome, rheumatoid arthritis, Crohn's disease, Stevens Johnson syndrome, as well as toxic epidermal necrolysis or mucous membrane pemphigoid.

Infliximab is an antibody against tumour necrosis factor alpha and has been used to treat or prevent corneal melt in certain patients with inflammatory of auto-immune disease. In this situation, infliximab was used intravenous (using veins) in order to treat the whole body.

This study's hypothesis is that infliximab can safely be used as eye drops for the treatment of sterile corneal melt.

Detailed description: This is an unmasked, prospective, single-center trial of twelve patients with sterile corneal melt and an underlying auto-immune or inflammatory disease, such as rosacea, Sjogren's syndrome, rheumatoid arthritis, Crohn's disease, Stevens Johnson syndrome, as well as toxic epidermal necrolysis or mucous membrane pemphigoid.

The aim of this phase I study is to evaluate the safety and tolerability of topical infliximab 10mg/ml eye drops for the treatment of corneal melt. As such, six (6) subjects will be recruited in the experimental treatment study and six (6) subjects will be enrolled in the parallel observational study. Indeed, candidates having all inclusion criteria but one exclusion criteria (which are contraindication to infliximab use), will be recruited in the observational study, will receive the standard treatment without infliximab.

During the treatment period, subjects in the therapeutic study will receive topical infliximab 10mg/ml four (4) times per day for four (4) weeks. In order to determine the safety profile, potential side effects as well as the course of the disease, subjects will be monitored while on the study medication as well as for 8 weeks following discontinuation of the drug. The ophthalmological follow-up will be identical in the two groups. However, only subjects enrolled in the experimental treatment study will receive additional laboratory tests. The total study duration for each patient will be 12 weeks.

In terms of statistical analysis, the investigators will focus on describing the outcome measured in the study. For instance, the investigators will describe the number and proportion of side effects, the number of patients with a quiescent corneal melt at 4 weeks and the patients who required a tectonic surgery at 12 weeks post-treatment. The investigators will report the average and standard of deviation of the OSDI score, the epithelial deficit surface as well as the minimal corneal thickness. Moreover, the investigators will perform exploratory statistical analysis in order to study the disease course of each subject and comparing the addition of infliximab to the standard.

Eligibility criteria: Inclusion Criteria:

* Age 18 to 80 years;
* Any degree of active sterile corneal melting , as documented by slit-lamp examination, showing an epithelial defect and stromal thinning;
* Negative work-up for local and systemic infectious causes
* Negative corneal cultures (may show growth of common contaminants)
* Capable of providing informed consent;
* Capable of administering eye drops either themselves or through a caregiver.

Exclusion Criteria:

* Any active ocular or systemic infection including active or latent tuberculosis, histoplasmosis, coccidiomycosis, cytomegalovirus, pneumocystosis, aspergillosis, or hepatitis B.
* History of neoplasia diagnosed within the last 5 years
* Demyelinating disease
* Diabetes
* Congestive heart failure
* Significant anomalies on complete blood count, creatinine or hepatic enzymes
* Pregnancy or breast feeding
* Allergy to infliximab or to the drug vehicle (Refresh liquigel)
* Past or present use of anti-TNF-α medications or human interleukin-1 receptor antagonist (anakinra, IL-1Ra)

Primary outcomes:
measure: Adverse Events
timeFrame: 12 weeks
measure: Percentage of patients finishing 4 weeks of infliximab use
timeFrame: 4 weeks
Secondary outcomes:
measure: Visual Acuity
timeFrame: 4 and 12 weeks
measure: Ocular surface symptoms as assessed by ocular disease index score
timeFrame: 4 and 12 weeks
measure: Conjunctival hyperemia using a slit-lamp photographs
timeFrame: 4 and 12 weeks
measure: Corneal thickness as measured by anterior segment optical coherence tomography
timeFrame: 4 weeks
measure: Surface area of the corneal melt using a slit-lamp photographs
timeFrame: 4 weeks
measure: Quiescent corneal state
timeFrame: 4 weeks
measure: Eyes requiring tectonic surgery
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: Centre Hospitalier de l'Université de Montréal
state: Quebec
Study officials:
affiliation: Centre hospitalier de l'Université de Montréal (CHUM)
name: Marie-Claude Robert, MD
role: PRINCIPAL_INVESTIGATOR
References: