Topical Infliximab in Autoimmune Eyes With Keratoprosthesis

Stevens-Johnson Syndrome Clinical Trial

Official title:

Topical Infliximab in Autoimmune Eyes With Keratoprosthesis

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02126020
• Other study ID #: MEEI 13-110H
• Secondary ID: IND 122719
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• First received: April 27, 2014
• Last updated: April 5, 2017
• Start date: November 2014
• Est. completion date: April 3, 2017

Study information

• Verified date: April 2017
• Source: Massachusetts Eye and Ear Infirmary
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: April 3, 2017
• Est. primary completion date: April 3, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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-a 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

Related Conditions & MeSH terms

• Mucous Membrane Pemphigoid
• Pemphigoid, Bullous
• Stevens-Johnson Syndrome
• Syndrome
• Toxic Epidermal Necrolysis (Lyell) Syndrome

Intervention

Drug:
• topical infliximab
topical infliximab administered QID for 3 months followed by BID for 9 months

Locations

Country	Name	City	State
Canada	Centre Hospitalier de l'Université de Montréal	Montréal	Quebec
United States	Massachusetts Eye and Ear Infirmary	Boston	Massachusetts

Sponsors (3)

Lead Sponsor	Collaborator
James Chodosh, MD, MPH	Fonds de recherche en ophtalmologie de l'Université de Montréal (FROUM), Massachusetts Eye and Ear Infirmary

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tolerability	Percentage of patients finishing 12 months of topical infliximab use	1 year
Primary	Adverse events	Number and type of adverse events	2 years
Primary	rate of corneal melting	rate of corneal melting or ulceration during infliximab prophylaxis (12 months) and after the drug is stopped (following 12 months)	2 years
Primary	KPro retention	Percentage of retained KPros at 2 years	2 years
Secondary	Visual acuity		2 years
Secondary	Ocular surface symptoms	Ocular surface symptoms as assessed by ocular surface disease index score	2 years
Secondary	Ocular surface inflammation	Ocular surface inflammation using slit-lamp photographs and the ocular redness index (ORI)	2 years
Secondary	tear matrix metalloproteinase (MMP)	Levels and activity of MMPs, myeloperoxidase and tissue inhibitor of MMP-1	2 years
Secondary	graft thickness	Corneal carrier graft thickness as measured by anterior segment optical coherence tomography before, during and after treatment with infliximab	2 years