Topical Infliximab for Glaucoma

Recruiting at 1 trial location

Overseen By Zobelle Tchouaga

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)

Must not be taking: Anti-TNF-α, Anti-inflammatory biologics

Disqualifiers: Diabetes, Heart failure, Malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 3 months

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether infliximab, an anti-inflammatory medication, can be safely used as eye drops after cornea surgery to prevent glaucoma, a common complication. Participants will be divided into two groups: one using infliximab eye drops and the other following the standard post-surgery routine without the drops. This trial suits those undergoing their first cornea transplant who can manage eye medication or have assistance. As a Phase 1, Phase 2 trial, it aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you have used anti-TNF-α medication or other anti-inflammatory biologics before.

Is there any evidence suggesting that topical infliximab is likely to be safe for humans?

Research shows that topical infliximab, a drug that reduces inflammation, is being tested for safety and effectiveness in treating eye conditions. Some studies have examined its use in eye surgeries, and so far, no major safety issues have emerged.

For example, one study examined its use after glaucoma surgery and found it reduced unwanted healing without causing significant side effects. Another study is investigating its potential to prevent glaucoma after cornea surgery. Although the full results aren't available yet, no major safety concerns have been reported.

Since this is an early trial, researchers continue to monitor for any side effects. However, studies so far suggest it is generally safe when used on the eye. If considering joining a trial, this information might help you feel more comfortable about the treatment's safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for glaucoma?

Unlike the standard treatments for glaucoma, which typically include eye drops to reduce intraocular pressure or surgical procedures, topical infliximab offers a novel approach by targeting inflammation directly on the eye's surface. Infliximab is a monoclonal antibody that blocks tumor necrosis factor-alpha (TNF-alpha), a key player in the inflammatory process that can contribute to tissue damage. Researchers are excited about this treatment because it uses a topical delivery method, potentially offering fewer systemic side effects compared to traditional oral or injectable forms of infliximab. This new approach could provide an effective option for patients who undergo PKP surgery and need to manage post-operative inflammation.

What evidence suggests that topical infliximab might be an effective treatment for glaucoma?

Research has shown that infliximab eye drops might help prevent inflammation-related problems after cornea surgery. In this trial, some participants will receive topical infliximab following PKP surgery to evaluate its effectiveness in reducing the body's wound healing response in the eye, which is crucial for managing the risk of glaucoma after surgery. Although another study found that infliximab did not improve outcomes in a specific type of glaucoma surgery, it still demonstrated promise in controlling inflammation. This suggests that infliximab eye drops could lower the chance of developing glaucoma by managing inflammation after surgery. Overall, they show potential as a treatment for inflammation-related eye issues. ^{1 2 3 4 6}

Who Is on the Research Team?

Marie-Claude Robert, MD

Principal Investigator

CHUM

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 undergoing their first corneal transplant surgery who can consent and manage eye medication (or have someone to help). It's not for those with active eye infections, past transplants, severe glaucoma or macular disease, systemic infections, recent cancer, demyelinating diseases, diabetes or heart failure (NYHA class III/IV), pregnant/breastfeeding women, infliximab allergies, abnormal blood counts or liver tests.

Inclusion Criteria

I can put in my eye medication or have someone who can do it for me.

I am having my first corneal transplant surgery.

I can understand and agree to the study's details.

Exclusion Criteria

Significant anomaly of complete blood count or hepatic enzymes

I have had a corneal transplant in the past.

I currently have an eye infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive topical infliximab 10mg/ml eye drops four times per day for 3 months

3 months

Regular visits for monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Regular visits for monitoring

What Are the Treatments Tested in This Trial?

Interventions

• Topical Infliximab

Trial Overview

The study aims to test if using infliximab eye drops after corneal transplant surgery is safe and can prevent glaucoma. Participants will either receive the topical infliximab drops or no treatment as a comparison. The main focus is on safety and effectiveness in preventing inflammation that could lead to glaucoma.

How Is the Trial Designed?

Group I: Topical infliximab following PKP surgery Experimental Treatment 1 Intervention

Additionally to standard post-operative regimen, patients who will be undergoing their first PKP surgery and who meet all inclusion and no exclusion criteria will be included in the experimental group. These patients will administer topical infliximab four times per day for 3 months.

Group II: No topical infliximab following PKP surgery Active Control 1 Intervention

Patients who will be undergoing their first PKP surgery, but who are not qualified to receive infliximab or who refuse to receive infliximab, will be included in the control group. These patients will only administer the standard post-operative regimen following their PKP surgery and will not administer topical infliximab. They will be followed with the same follow-up schedule, questionnaires, examinations and non-invasive tests (excluding lab work) as patients in the interventional group.

Topical Infliximab is already approved in United States, European Union, Japan for the following indications:

Approved in United States as Remicade for:

• Rheumatoid arthritis
• Adult and pediatric Crohn’s disease
• Ankylosing spondylitis
• Psoriatic arthritis
• Plaque psoriasis
• Adult and pediatric ulcerative colitis

Approved in European Union as Remicade for:

• Rheumatoid arthritis
• Crohn’s disease
• Ankylosing spondylitis
• Psoriatic arthritis
• Plaque psoriasis
• Ulcerative colitis

Approved in Japan as Remicade for:

• Ocular Behçet’s disease
• Rheumatoid arthritis
• Crohn’s disease
• Ankylosing spondylitis
• Psoriatic arthritis
• Plaque psoriasis
• Ulcerative colitis

Who Is Running the Clinical Trial?

Centre hospitalier de l'Université de Montréal (CHUM)

Lead Sponsor

Trials

389

Recruited

143,000+

Ottawa Hospital Research Institute

Collaborator

Trials

585

Recruited

3,283,000+

Prism Eye Institute

Collaborator

Trials

4

Recruited

460+

Fonds de recherche en ophtalmologie de l'Université de Montréal

Collaborator

Trials

6

Recruited

160+

Maisonneuve-Rosemont Hospital

Collaborator

Trials

102

Recruited

38,300+

Niagara Health System

Collaborator

Trials

9

Recruited

2,800+

Published Research Related to This Trial

In a study of 82 pediatric patients receiving infliximab (IFX) for rheumatologic and ocular inflammatory diseases, infusion reactions (IR) occurred in 17% of patients, with the majority being mild to moderate in severity.

Despite experiencing IR, over 50% of patients were able to continue treatment with IFX by using premedication strategies such as antihistamines and corticosteroids, indicating a manageable safety profile for ongoing therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infliximab in pediatric rheumatology patients: a retrospective analysis of infusion reactions and severe adverse events during 2246 infusions over 12 years. Aeschlimann, FA., Hofer, KD., Cannizzaro Schneider, E., et al.[2015]

Infliximab, an anti-TNF-alpha monoclonal antibody, was studied in 771 patients for Crohn's disease and rheumatoid arthritis, showing an acceptable safety profile with only 17% experiencing acute infusion reactions compared to 7% in the placebo group.

While infliximab was associated with a higher overall rate of infections (26% vs. 16% for placebo), there was no increased risk of serious infections or difference in mortality rates, indicating it is generally safe for use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long term safety of infliximab. Schaible, TF.[2019]

A 26-year-old female with ulcerative colitis experienced resolution of infusion-related hypersensitivity reactions after switching from the original infliximab to the biosimilar infliximab-dyyb, indicating that the biosimilar may be a safer option for some patients.

The case highlights the importance of recognizing differences in inactive ingredients between biologics, as these may contribute to adverse reactions, suggesting that switching to a biosimilar could be beneficial for patients with such sensitivities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

P013 Resolution of Infliximab Associated Infusion Hypersensitivity After Switching to Biosimilar Infliximab-dyyb. Irani, M., Bryant, R., Lofton, H., et al.[2023]

Infliximab (IFX) is an effective treatment for inflammatory bowel diseases (IBD) and other immune-mediated conditions, but it comes with various safety concerns that need to be managed.

The Austrian Society of Gastroenterology and Hepatology created a comprehensive checklist to ensure the safe use of IFX, addressing potential adverse events like infections, infusion reactions, and complications in different patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A decade of infliximab: The Austrian evidence based consensus on the safe use of infliximab in inflammatory bowel disease. Miehsler, W., Novacek, G., Wenzl, H., et al.[2021]

TNF-α blockers, particularly infliximab, show promise in treating eye conditions like diabetic macular edema and age-related macular degeneration, but their safety for intravitreal use is concerning due to reported inflammatory responses.

Current data suggests that while TNF-α blockers are effective for inflammatory diseases, their application in ophthalmology as an off-label treatment for noninfectious uveitis raises safety issues, necessitating further studies on dosing and alternative formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-tumor necrosis factor alpha for retinal diseases: current knowledge and future concepts. Mirshahi, A., Hoehn, R., Lorenz, K., et al.[2021]

In a study of 25 patients with refractory uveitis-related macular edema, both infliximab and adalimumab showed similar efficacy in reducing central foveal thickness over 6 and 24 months, with no significant differences between the two treatments.

At the 6-month mark, 50% of patients on adalimumab and 61% on infliximab responded to treatment, indicating that both medications are effective options for managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

INFLIXIMAB and ADALIMUMAB in Uveitic Macular Edema. Lejoyeux, R., Diwo, E., Vallet, H., et al.[2018]

Infliximab, an anti-tumor necrosis factor alpha medication, successfully suppressed inflammation in five cases of orbital inflammatory diseases and chronic relapsing inflammatory optic neuropathy that were unresponsive to other treatments.

While infliximab provided relief from symptoms and signs of inflammation, the effects were not permanent, as symptoms returned around week 5, indicating it may be a valuable alternative to steroids for managing refractory inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of infliximab in ocular inflammation. Prendiville, C., O'Doherty, M., Moriarty, P., et al.[2015]

Infliximab can be safely injected into the eye of rabbits at doses up to 1.7 mg, with no significant ocular side effects observed in clinical examinations or electroretinography tests.

At a higher dose of 3.3 mg, some rabbits showed nerve fiber edema, indicating that while lower doses are safe, higher doses may pose risks, suggesting careful dose management is necessary for potential human applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot study on ocular safety of intravitreal infliximab in a rabbit model. Giansanti, F., Ramazzotti, M., Vannozzi, L., et al.[2015]

In a study of 177 patients with refractory uveitis due to Behçet's disease, both infliximab (IFX) and adalimumab (ADA) were effective treatments, but ADA showed significantly better outcomes in anterior chamber inflammation, vitritis, and best-corrected visual acuity after one year.

The retention rate for ADA was higher than for IFX (95.24% vs. 84.95%), suggesting that patients may prefer ADA as a first-line biologic treatment for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Study of Infliximab Versus Adalimumab in Refractory Uveitis due to Behçet's Disease: National Multicenter Study of 177 Cases. Atienza-Mateo, B., Martín-Varillas, JL., Calvo-Río, V., et al.[2020]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4018311/

Topical infliximab for the suppression of wound healing ...

Our study suggests that topical infliximab effectively suppresses the subconjunctival wound healing response after experimental glaucoma filtration surgery.

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC5693834/

A Pilot Study on Ocular Safety and Efficacy of Infliximab as ...

Infliximab did not appear to improve outcomes in this model of glaucoma filtration surgery. Bleb survival was significantly higher in the MMC ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05180994

Topical Infliximab in Eyes With Penetrating Keratoplasty

The current study aims to evaluate whether using topical infliximab 10mg/ml eye drops is safe and efficient to prevent the emergence of glaucoma of inflammatory ...

4.

withpower.com

withpower.com/trial/phase-2-glaucoma-1-2022-9ee99

Topical Infliximab for Glaucoma

Trial Overview The study aims to test if using infliximab eye drops after corneal transplant surgery is safe and can prevent glaucoma. Participants will either ...

5.

sciencedirect.com

sciencedirect.com/science/article/pii/S2162098923005509

Infliximab in the Treatment of Refractory Ocular ...

We collected data regarding the visual acuity, status of inflammation, and any complications arising from the treatment. Results. Seven eyes from 3 male and 2 ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05180994?id=%22NCT05180994%22&rank=1

Topical Infliximab in Eyes With Penetrating Keratoplasty

An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...