Cyclosporine A + Natamycin for Fungal Keratitis

(FANCY Trial)

Recruiting at 1 trial location

Overseen By Thomas Lietman, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University of California, San Francisco

Must not be taking: Cyclosporine, Steroids

Disqualifiers: Bacterial, Viral, Pregnancy, others

Stay on Your Current Meds You can continue your current medications while participating

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: Unknown

Duration: 9 weeks

150 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to learn if adjunctive topical Cyclosporine A eye drops combined with standard of care topical Natamycin treatment improves vision outcomes in patients with fungal keratitis.

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 are already using cyclosporine eye drops.

What data supports the effectiveness of the drug Cyclosporine A for treating fungal keratitis?

Cyclosporine A has been shown to be effective in treating other conditions like psoriasis and atopic dermatitis, where it significantly reduced symptoms. This suggests it may also help in managing fungal keratitis, especially since it has been investigated as a substitute for corticosteroids in similar eye conditions. ^{1 2 3 4 5}

Is Cyclosporine A safe for use in humans?

Cyclosporine A, also known as Neoral, Sandimmune, and other names, has been studied for safety in various conditions like renal and liver transplants, psoriasis, and atopic dermatitis. These studies generally show that it is well-tolerated and safe, with side effects typical of its class, such as changes in kidney function and blood pressure, but it requires careful dose management. ^{3 6 7 8 9}

How does the drug Cyclosporine A + Natamycin differ from other treatments for fungal keratitis?

Cyclosporine A + Natamycin is unique because it combines an immunosuppressant (Cyclosporine A) with an antifungal (Natamycin), potentially enhancing the treatment of fungal keratitis by reducing inflammation and directly targeting the fungal infection. This combination may offer a novel approach compared to using Natamycin alone or in combination with other antifungals like voriconazole. ^{10 11 12 13 14}

Research Team

Gerami Seitzman, MD

Principal Investigator

UCSF Proctor Foundation

Eligibility Criteria

This trial is for patients with different types of corneal ulcers, specifically those caused by fungal infections. Participants should have a diagnosis of fungal keratitis or bacterial keratitis and be suitable for treatment with eye drops.

Inclusion Criteria

Inclusion of 20/40 = 6/12 = 0.3 Log MAR and 20/400 = 3/60 = +1.3 Log MAR

Smear or culture positive for fungal keratitis, any length

I am 18 years old or older.

Exclusion Criteria

I have an eye infection caused by bacteria or a virus.

Presenting acuity better than 20/40 = 6/12 = 0.3 Log MAR or worse than 20/400 = 3/60 = +1.3 Log MAR

I have had a corneal perforation.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive hourly natamycin eye drops for one week, followed by either Cyclosporine A 0.1%, Cyclosporine A 2%, or placebo for one month, then twice a day for another month

9 weeks

Follow-up

Participants are monitored for best corrected visual acuity (BCVA) at 3 months

3 months

Treatment Details

Interventions

• Cyclosporine A

Trial Overview The study is testing if adding Cyclosporine A eye drops to the usual Natamycin treatment helps improve vision in patients with fungal keratitis better than a placebo (a substance with no active drug).

Participant Groups

Group I: Cyclosporine A (CsA) 2% Experimental Treatment 1 Intervention

After one week of hourly natamycin eye drops the participants in this arm will use this drop four times a day for one month then twice a day for one month.

Group II: Cyclosporine A (CsA) 0.1% Experimental Treatment 1 Intervention

After one week of hourly natamycin eye drops the participants in this arm will use this drop four times a day for one month then twice a day for one month.

Group III: Placebo Placebo Group 1 Intervention

After one week of hourly natamycin eye drops the participants in this arm will use this drop four times a day for one month then twice a day for one month.

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Aravind Eye Hospitals, India

Collaborator

Trials

12

Recruited

2,500+

Aravind Eye Care System

Collaborator

Trials

13

Recruited

102,000+

Findings from Research

In a pilot study involving 14 patients with atopic dermatitis, Neoral (a microemulsion of cyclosporin A) showed significantly greater improvement in disease activity and extent of disease compared to Sandimmun after just 2 weeks of treatment.

Both Neoral and Sandimmun were found to be effective and well tolerated over 8 weeks, but Neoral's faster onset of action suggests it could be a preferable option for initial treatment of severe atopic dermatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of two formulations of cyclosporin A in the treatment of severe atopic dermatitis. Aa double-blind, single-centre, cross-over pilot study. Zurbriggen, B., Wüthrich, B., Cachelin, AB., et al.[2017]

References

1. England pubmed.ncbi.nlm.nih.gov

Efficacy and pharmacokinetics of two formulations of cyclosporine A in patients with psoriasis. [2019]

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

Topical cyclosporin A in the management of therapeutic keratoplasty for mycotic keratitis. [2019]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Comparison of two formulations of cyclosporin A in the treatment of severe atopic dermatitis. Aa double-blind, single-centre, cross-over pilot study. [2017]

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

Clinical experience with the use of cyclosporin A in psoriasis. Results of a retrospective study. [2013]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Comparison of two cyclosporine formulations in healthy Middle Eastern volunteers: bioequivalence of the new Sigmasporin Microoral and Sandimmun Neoral. [2019]

6. Switzerland pubmed.ncbi.nlm.nih.gov

UK multicentre study to assess the safety and tolerability of Neoral in stable renal transplant patients. UK Neoral Study Group. [2019]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Conversion of psoriasis patients from the conventional formulation of cyclosporin A to a new microemulsion formulation: a randomized, open, multicentre assessment of safety and tolerability. [2018]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and tolerability of a new oral formulation of cyclosporin A, Sandimmun Neoral, in renal transplant patients. [2019]

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

An open-label study of the safety and tolerability of converting stable liver transplant recipients to neoral. [2019]

10. Pakistan pubmed.ncbi.nlm.nih.gov

Natamycin versus natamycin combined with voriconazole in the treatment of fungal keratitis. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Re-appraisal of topical 1% voriconazole and 5% natamycin in the treatment of fungal keratitis in a randomised trial. [2015]

12. India pubmed.ncbi.nlm.nih.gov

Natamycin in the treatment of keratomycosis: correlation of treatment outcome and in vitro susceptibility of fungal isolates. [2021]

13. China pubmed.ncbi.nlm.nih.gov

Natamycin in the treatment of fungal keratitis: a systematic review and Meta-analysis. [2022]

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

The mycotic ulcer treatment trial: a randomized trial comparing natamycin vs voriconazole. [2022]