Topical Infliximab for Corneal Melt

Overseen By Marie-Claude Robert, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

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

Must not be taking: Anti-TNF, Anakinra

Disqualifiers: Infections, Neoplasia, Diabetes, Heart failure, 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: 4 weeks

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for corneal melt, a serious eye condition where the eye’s surface thins dangerously. Instead of the usual intravenous infliximab treatment, the study tests the safety and effectiveness of infliximab as eye drops (topical infliximab). It targets individuals with sterile corneal melt from conditions like rheumatoid arthritis or Sjogren's syndrome. Participants must have active corneal melting without infections and be able to use eye drops. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are currently using anti-TNF-α medications or human interleukin-1 receptor antagonist, you may not be eligible to participate.

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

Research has shown that using infliximab as eye drops may help treat conditions like corneal melt. In studies with mice, applying infliximab directly to the eye greatly reduced the chances of the cornea developing holes or tears. This suggests that the treatment could help prevent serious eye damage.

Regarding safety, past studies using infliximab for eye issues did not report any serious side effects or problems. This is promising, but it's important to remember that the research is still in the early stages. The treatment has shown promise in animal studies and some human cases, but more information is needed to confirm these results in larger groups of people.

Overall, while early results are encouraging, the treatment is still being tested for safety and effectiveness in humans. Participants in clinical trials will help researchers gather more information. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for corneal melt, which often include oral medications and surgical interventions, topical infliximab offers a novel approach by delivering the medication directly to the eye's surface. This method could enhance the drug's effectiveness while minimizing systemic side effects. Researchers are excited about this treatment because it targets the inflammatory processes at the root of corneal melt more precisely, potentially leading to quicker and more localized relief for patients.

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

Research has shown that infliximab, a type of antibody, can effectively treat corneal melt, a condition where the cornea, the clear front part of the eye, begins to break down. In past cases, infliximab helped patients with corneal issues related to rheumatoid arthritis by stabilizing the cornea and preventing further damage. A study in mice found that using infliximab as an eye treatment reduced the chances of the cornea developing holes by about 50%. In this trial, participants in the experimental group will receive topical infliximab alongside standard treatment, which may help protect and heal the cornea in patients with sterile corneal melt. ^{2 3 4 5 6}

Who Is on the Research Team?

Marie-Claude Robert, MD

Principal Investigator

Centre hospitalier de l'Université de Montréal (CHUM)

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 with active sterile corneal melting, which isn't caused by an infection. Participants must be able to give consent and use eye drops themselves or with help. They can't have used certain immune system drugs, have a recent cancer history, heart failure, demyelinating disease, diabetes, be pregnant/breastfeeding or allergic to the study drug.

Inclusion Criteria

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

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

I have a condition where my cornea is thinning and has an open sore, confirmed by an eye exam.

Exclusion Criteria

Pregnancy or breast feeding

I was diagnosed with cancer within the last 5 years.

I have used medications like anti-TNF or anakinra in the past or currently.

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

4 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Bi-weekly visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Topical Infliximab

Trial Overview The trial tests if Infliximab eye drops are safe for treating sterile corneal melt—a serious condition where the clear front part of the eye thins without infection. The hypothesis is that applying Infliximab directly to the eyes might prevent damage and preserve vision.

How Is the Trial Designed?

Group I: Topical Infliximab Experimental Treatment 1 Intervention

Additionally to standard treatment, patients with all inclusive criteria and none exclusive criteria will be included in the therapeutic group and will receive topical infliximab QID for 4 weeks.

Group II: Observational group Active Control 1 Intervention

Patients with all inclusive criteria and one exclusive criteria will receive the standard treatment, without topical infliximab.

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+

Fonds de recherche en ophtalmologie de l'Université de Montréal

Collaborator

Trials

6

Recruited

160+

Published Research Related to This Trial

In a study of 2294 children with juvenile idiopathic arthritis (JIA), those treated with biologics (etanercept, adalimumab, infliximab) had a lower occurrence of newly diagnosed uveitis compared to those receiving methotrexate (MTX), although this difference was not statistically significant.

The analysis suggested that etanercept may have a protective effect against uveitis, but this could be influenced by confounding factors, such as younger age and earlier disease stage in the MTX group, which are associated with a higher risk of developing uveitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The risk of uveitis in patients with JIA receiving etanercept: the challenges of analysing real-world data. Davies, R., De Cock, D., Kearsley-Fleet, L., et al.[2021]

In a study of 27 patients with noninfectious ocular inflammatory disease resistant to traditional treatments, infliximab therapy resulted in over 90% of patients achieving inflammation control within 12 months.

The therapy not only improved inflammation but also allowed 16 patients to reduce or stop their other immunomodulatory medications, with a low incidence of adverse effects, as only one patient had to discontinue treatment due to side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infliximab therapy for the treatment of refractory ocular inflammatory disease. Sobrin, L., Kim, EC., Christen, W., et al.[2015]

Rituximab (RTX) was effective in treating severe uveitis associated with juvenile idiopathic arthritis (JIA) in a study of 10 patients, achieving uveitis inactivity in 7 patients for an average of 7.5 months after one treatment cycle.

The treatment not only helped control uveitis but also improved arthritis symptoms in 7 out of the 10 patients, suggesting RTX could be a valuable rescue therapy for cases resistant to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of severe uveitis associated with juvenile idiopathic arthritis with anti-CD20 monoclonal antibody (rituximab). Heiligenhaus, A., Miserocchi, E., Heinz, C., et al.[2022]

Intravenous infliximab was used to treat tissue melt in four patients who had undergone Boston keratoprosthesis (B-KPro) due to autoimmune conditions, showing significant reduction in inflammation and halting the melting process in some cases.

Despite its effectiveness as a potential sight-saving treatment, challenges such as high cost, patient adherence, and infusion reactions were noted as limitations to its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infliximab after Boston Keratoprosthesis in Stevens-Johnson Syndrome: An Update. Robert, MC., Črnej, A., Shen, LQ., et al.[2022]

A 37-year-old male experienced severe infusion-related angioedema after receiving the infliximab biosimilar (infliximab-abda), highlighting the potential for serious allergic reactions similar to those seen with the original infliximab.

The patient's angioedema was effectively managed with supportive care and discontinuation of the biosimilar, leading to resolution of symptoms after a 4-day hospital stay, indicating that while biosimilars can be effective, they may still carry risks of adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infusion-related angioedema associated with infliximab-abda: Case report. Herndon, K., Dewitt, A., Gillion, A., et al.[2021]

Infliximab, a TNFalpha antagonist, was effective in treating three patients with rheumatoid arthritis-associated peripheral ulcerative keratitis who did not respond to conventional immunosuppressant therapies.

All patients showed significant improvement, including reduced eye inflammation and healing of corneal defects, indicating that infliximab can be a valuable treatment option for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapy of progressive rheumatoid arthritis-associated corneal ulceration with infliximab. Thomas, JW., Pflugfelder, SC.[2022]

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]

In a study of 154 patients with juvenile idiopathic arthritis (JIA) associated uveitis treated for at least 2 years, adalimumab (ADA) demonstrated a significantly higher clinical remission rate (60.0%) compared to infliximab (IFX) (20.3%).

ADA also resulted in fewer ocular complications and a lower incidence of minor adverse events compared to IFX, indicating a better safety profile for ADA in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Longterm Safety and Efficacy of Adalimumab and Infliximab for Uveitis Associated with Juvenile Idiopathic Arthritis. Cecchin, V., Zannin, ME., Ferrari, D., et al.[2019]

In a study of 650 biologic-naïve patients with moderate to severe rheumatoid arthritis, the biosimilar PF-06438179/GP1111 showed similar efficacy to the reference infliximab (Remicade®) at week 14, with ACR20 response rates of 62.7% and 64.1%, respectively, indicating that the biosimilar is an effective alternative.

Both PF-06438179/GP1111 and infliximab-EU had comparable safety profiles and immunogenicity rates, with no significant differences in adverse effects or antibody development, suggesting that the biosimilar is as safe as the reference product.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized controlled trial comparing PF-06438179/GP1111 (an infliximab biosimilar) and infliximab reference product for treatment of moderate to severe active rheumatoid arthritis despite methotrexate therapy. Cohen, SB., Alten, R., Kameda, H., et al.[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]

A study involving 213 healthy subjects found that the pharmacokinetics (PK) of the biosimilar infliximab (CT-P13) is highly similar to both the European (EU-RMP) and US (US-RMP) reference products, indicating that CT-P13 can be expected to perform similarly in the body as the original medications.

All three formulations (CT-P13, EU-RMP, and US-RMP) demonstrated comparable safety and tolerability profiles, suggesting that CT-P13 is a safe alternative to the reference infliximab products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the pharmacokinetics and safety of three formulations of infliximab (CT-P13, EU-approved reference infliximab and the US-licensed reference infliximab) in healthy subjects: a randomized, double-blind, three-arm, parallel-group, single-dose, Phase I study. Park, W., Lee, SJ., Yun, J., et al.[2022]

In a study of 32 patients treated with infliximab for rheumatoid arthritis, 65.6% experienced adverse drug reactions (ADRs), with the most common being infections, including urinary and respiratory infections.

Among the ADRs, 12.5% were classified as serious, and some reactions led to the discontinuation of infliximab, highlighting the need for ongoing monitoring and further research on long-term safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Retrospective analysis of adverse effects of infliximab in a hospital rheumatology service]. Cabou, C., Bagheri, H., Cantagrel, A., et al.[2019]

Citations

1. withpower.com withpower.com/trial/phase-1-corneal-ulcer-8-2017-3bf1b

Topical Infliximab for Corneal Melt Infliximab, a TNFalpha antagonist, was effective in treating three patients with rheumatoid arthritis-associated peripheral ulcerative keratitis who did not ...

2. ctv.veeva.com ctv.veeva.com/study/topical-infliximab-for-sterile-corneal-melt

Topical Infliximab for Sterile Corneal Melt - ClinicalTrials.Veeva The aim of this phase I study is to evaluate the safety and tolerability of topical infliximab 10mg/ml eye drops for the treatment of corneal ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3369392/

Stabilization of Bilateral Progressive Rheumatoid Corneal ... We describe the use of infliximab to stabilize progressive and recurrent corneal melting in bilateral tectonic penetrating keratoplasties for PUK associated ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2162098923005509

Infliximab in the Treatment of Refractory Ocular ... All patients achieved quiescence after 3 doses of infliximab infusions during the period of 3 months. Most of the patients retained a useful visual acuity of 20 ...

5. iovs.arvojournals.org iovs.arvojournals.org/article.aspx?articleid=2165947

Safety and Efficacy of Topical Infliximab in a Mouse Model of ... Topical infliximab improved various clinical outcomes in the alkali burn model. (A) Corneal perforation rate was significantly reduced by approximately 50% ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02126020

Topical Infliximab in Autoimmune Eyes With Keratoprosthesis 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.