Topical Infliximab for Corneal Melt

Recruiting in Palo Alto (17 mi)

Overseen by Marie-Claude Robert, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

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

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests infliximab eye drops on patients with severe eye thinning due to autoimmune diseases. The drops aim to reduce inflammation by blocking a harmful protein. The study will check if these drops are safe and effective. Infliximab has been used effectively in various forms of eye inflammation, including uveitis and scleritis, often when other treatments have failed.

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.

What data supports the effectiveness of the drug Topical Infliximab for Corneal Melt?

Research shows that infliximab, a drug that blocks a protein causing inflammation, has been effective in treating eye conditions related to autoimmune diseases, such as corneal ulceration and tissue melt, which are similar to corneal melt. ^{1 2 3 4 5}

Is topical infliximab generally safe for humans?

Infliximab, used for various conditions, has been associated with some side effects like infusion reactions, infections, and allergic reactions. However, these studies mainly focus on its use in conditions like inflammatory bowel disease and rheumatoid arthritis, not specifically for corneal melt. ^{6 7 8 9 10}

How is the drug topical infliximab unique for treating corneal melt?

Topical infliximab is unique because it is applied directly to the eye, unlike other treatments for corneal melt that may not use this direct approach. Infliximab is a TNF-alpha antagonist, which means it blocks a protein that causes inflammation, and it has been used successfully in other eye-related inflammatory conditions. ^{1 3 4 11 12}

Research Team

Marie-Claude Robert, MD

Principal Investigator

Centre hospitalier de l'Université de Montréal (CHUM)

Eligibility Criteria

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 am between 18 and 80 years old.

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.

Exclusion Criteria

I was diagnosed with cancer within the last 5 years.

Pregnancy or breast feeding

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

Trial 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

4 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Bi-weekly visits (in-person)

Treatment Details

Interventions

• Topical Infliximab (Monoclonal Antibodies)

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.

Participant Groups

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 Japan for the following indications:

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+

Dr. Réjean Lapointe

Centre hospitalier de l'Université de Montréal (CHUM)

Chief Medical Officer since 2023

MD from Université de Montréal

Dr. Fabrice Brunet

Centre hospitalier de l'Université de Montréal (CHUM)

Chief Executive Officer since 2015

MD from Université de Montréal

Fonds de recherche en ophtalmologie de l'Université de Montréal

Collaborator

Trials

6

Recruited

160+

Findings from Research

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]

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]

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 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]

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]

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]

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]

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]

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]

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]

References

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

Therapy of progressive rheumatoid arthritis-associated corneal ulceration with infliximab. [2022]

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

Infliximab after Boston Keratoprosthesis in Stevens-Johnson Syndrome: An Update. [2022]

3. Canada pubmed.ncbi.nlm.nih.gov

Longterm Safety and Efficacy of Adalimumab and Infliximab for Uveitis Associated with Juvenile Idiopathic Arthritis. [2019]

4. England pubmed.ncbi.nlm.nih.gov

The risk of uveitis in patients with JIA receiving etanercept: the challenges of analysing real-world data. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Treatment of severe uveitis associated with juvenile idiopathic arthritis with anti-CD20 monoclonal antibody (rituximab). [2022]

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

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

7. England 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. [2022]

8. 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]

9. England pubmed.ncbi.nlm.nih.gov

Infusion-related angioedema associated with infliximab-abda: Case report. [2021]

10. France pubmed.ncbi.nlm.nih.gov

[Retrospective analysis of adverse effects of infliximab in a hospital rheumatology service]. [2019]

11. England 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. [2019]

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

Infliximab therapy for the treatment of refractory ocular inflammatory disease. [2015]