Topical Infliximab in Autoimmune Eyes With Keratoprosthesis

NCT ID: NCT02126020

Last Updated: 2017-04-07

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1/PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-11-30
• Study Completion Date: 2017-04-03

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.

Conditions

Stevens-Johnson Syndrome; Toxic Epidermal Necrolysis (Lyell) Syndrome; Mucous Membrane Pemphigoid

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

topical infliximab

topical infliximab 10 mg/mL QID x 3 months followed by BID x 9 months

Group Type: EXPERIMENTAL

topical infliximab

Intervention Type: DRUG

topical infliximab administered QID for 3 months followed by BID for 9 months

Interventions

topical infliximab

topical infliximab administered QID for 3 months followed by BID for 9 months

Intervention Type: DRUG

Other Intervention Names

Remicade

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Massachusetts Eye and Ear Infirmary

OTHER

Sponsor Role: collaborator

Fonds de recherche en ophtalmologie de l'Université de Montréal

OTHER

Sponsor Role: collaborator

James Chodosh, MD, MPH

OTHER

Sponsor Role: lead

Responsible Party

James Chodosh, MD, MPH

Associate Director of the Cornea and Refractive Surgery Service, Director of Boston Keratoprosthesis Clinical Programs

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

James Chodosh, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Massachusetts Eye and Ear Infirmary

Claes H Dohlman, MD, PhD

Role: STUDY_CHAIR

Massachusetts Eye and Ear Infirmary

Mona Harissi-Dagher, MD

Role: STUDY_CHAIR

Centre hospitalier de l'Université de Montréal (CHUM)

Locations

Massachusetts Eye and Ear Infirmary

Boston, Massachusetts, United States

Centre Hospitalier de l'Université de Montréal

Montreal, Quebec, Canada

Countries

United States; Canada

Other Identifiers

IND 122719

Identifier Type: OTHER

Identifier Source: secondary_id

MEEI 13-110H

Identifier Type: -

Identifier Source: org_study_id