Topical Infliximab in Autoimmune Eyes With Keratoprosthesis

NCT02126020 | Withdrawn Phase 1

• 2 other identifiers: MEEI 13-110HIND 122719
• Study Type: interventional
• Target: N/A
• Locations: 2 countries
• Sites: 2

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.

Conditions

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

Keywords

Keratoprosthesis; corneal melt; keratolysis; Tumor necrosis factor alpha; infliximab; matrix metalloproteinase

Outcome Measures

Primary Outcomes (4)

• Tolerability

  Percentage of patients finishing 12 months of topical infliximab use

  1 year

• Adverse events

  Number and type of adverse events

  2 years

• 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

• KPro retention

  Percentage of retained KPros at 2 years

  2 years

Secondary Outcomes (5)

• Visual acuity

  2 years

• Ocular surface symptoms

  2 years

• Ocular surface inflammation

  2 years

• tear matrix metalloproteinase (MMP)

  2 years

• graft thickness

  2 years

Study Arms (1)

topical infliximab

EXPERIMENTAL

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

Drug: topical infliximab

Interventions

topical infliximab DRUG

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

Also known as: Remicade

topical infliximab

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• James Chodosh, MD, MPH: lead
• Massachusetts Eye and Ear Infirmary: collaborator
• Fonds de recherche en ophtalmologie de l'Université de Montréal: collaborator

Study Sites (2)

Massachusetts Eye and Ear Infirmary

Boston, Massachusetts, 02114, United States

Location

Centre Hospitalier de l'Université de Montréal

Montreal, Quebec, H2L 4M1, Canada

Location

MeSH Terms

Conditions

Stevens-Johnson Syndrome; Syndrome; Pemphigoid, Benign Mucous Membrane

Interventions

Infliximab

Condition Hierarchy (Ancestors)

Stomatitis; Mouth Diseases; Stomatognathic Diseases; Drug Eruptions; Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Erythema Multiforme; Erythema; Skin Diseases, Vesiculobullous; Hypersensitivity, Delayed; Hypersensitivity; Immune System Diseases; Drug Hypersensitivity; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Disease; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Conjunctival Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• James Chodosh, MD, MPH

  Massachusetts Eye and Ear Infirmary

  PRINCIPAL INVESTIGATOR

• Claes H Dohlman, MD, PhD

  Massachusetts Eye and Ear Infirmary

  STUDY CHAIR

• Mona Harissi-Dagher, MD

  Centre hospitalier de l'Université de Montréal (CHUM)

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Director of the Cornea and Refractive Surgery Service, Director of Boston Keratoprosthesis Clinical Programs

Study Record Dates

• First Submitted: April 27, 2014
• First Posted: April 29, 2014
• Study Start: November 1, 2014
• Primary Completion: April 3, 2017
• Study Completion: April 3, 2017
• Last Updated: April 7, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); CA (1)