Topical Infliximab for Glaucoma

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

Trial Summary

What is the purpose of this trial?

Penetrating keratoplasty is a cornea surgery involving several inflammatory complications, of which the most important is glaucoma. Researchers wish to determine whether it is safe to administer infliximab (an anti-inflammatory drug) eye drops after surgery, and whether this eye drop could prevent the occurrence of glaucoma.

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 topical infliximab safe for humans?

Infliximab has been used safely in humans for conditions like inflammatory bowel disease and rheumatoid arthritis, but it can cause some side effects like infusion reactions (headache, fever, chills) and infections. While these side effects are generally manageable, the safety of topical infliximab specifically for glaucoma hasn't been directly studied in humans yet. ^{1 2 3 4 5}

How is the drug Topical Infliximab unique for treating glaucoma?

Topical Infliximab is unique for treating glaucoma because it is applied directly to the eye, unlike traditional glaucoma treatments that are often oral or injected. It targets tumor necrosis factor alpha (TNF-α), a protein involved in inflammation, which is a novel approach compared to standard treatments that typically focus on reducing eye pressure. ^{1 6 7 8 9}

Research Team

Marie-Claude Robert, MD

Principal Investigator

CHUM

Eligibility Criteria

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 am between 18 and 80 years old.

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

I am having my first corneal transplant surgery.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

A pilot study on ocular safety of intravitreal infliximab in a rabbit model. [2015]

2. England pubmed.ncbi.nlm.nih.gov

A decade of infliximab: The Austrian evidence based consensus on the safe use of infliximab in inflammatory bowel disease. [2021]

3. Canada 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. [2015]

4. Canada pubmed.ncbi.nlm.nih.gov

Long term safety of infliximab. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

P013 Resolution of Infliximab Associated Infusion Hypersensitivity After Switching to Biosimilar Infliximab-dyyb. [2023]

6. England pubmed.ncbi.nlm.nih.gov

INFLIXIMAB and ADALIMUMAB in Uveitic Macular Edema. [2018]

7. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Anti-tumor necrosis factor alpha for retinal diseases: current knowledge and future concepts. [2021]

8. England pubmed.ncbi.nlm.nih.gov

The use of infliximab in ocular inflammation. [2015]

9. United States 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. [2020]