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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding Cyclosporine A eye drops to standard Natamycin treatment can improve vision in people with fungal keratitis, a type of eye infection. Two groups receive different strengths of Cyclosporine A, while one group receives a placebo. The trial seeks participants whose eye tests show a specific range of vision loss and who have a fungal infection confirmed by a smear or culture test. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Cyclosporine A (CsA) is generally safe for humans. In one study, patients using CsA 0.1% eye drops experienced improvements over a year, with most not encountering serious side effects.

Another study found that combining CsA with Natamycin can enhance vision in people with fungal eye infections. Although specific side effects were not detailed, the emphasis on improved vision suggests that any negative reactions were not significant compared to the benefits.

As Cyclosporine A undergoes testing in a Phase 3 trial, extensive safety information is already available. This phase typically involves more participants and provides detailed insights into the treatment's safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for fungal keratitis focus on antifungal agents like natamycin, which directly target the fungus. But researchers are excited about Cyclosporine A (CsA) because it works differently, by modulating the immune response to reduce inflammation in the eye. This trial is exploring two concentrations of CsA: 2% and 0.1%. The potential for CsA to complement existing antifungal treatments and enhance healing by reducing inflammation could make it a game-changer for patients suffering from this painful condition.

What evidence suggests that this trial's treatments could be effective for fungal keratitis?

This trial will evaluate the effectiveness of Cyclosporine A in different concentrations alongside Natamycin for treating fungal keratitis. Research has shown that using Cyclosporine A with Natamycin can greatly improve treatment for this serious eye infection. One study found that this combination helps patients see better, faster. Cyclosporine A reduces swelling in the eye, allowing Natamycin to fight the infection more effectively. This combined treatment has shown promising results in speeding up healing and improving vision. Early evidence suggests that adding Cyclosporine A to the usual treatment could significantly benefit those with this condition. Participants in this trial will receive either Cyclosporine A at 2%, Cyclosporine A at 0.1%, or a placebo, following initial treatment with Natamycin. ^{1 2 3 6 7}

Who Is on the Research Team?

Gerami Seitzman, MD

Principal Investigator

UCSF Proctor Foundation

Are You a Good Fit for This Trial?

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 willing to join the study.

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

Pregnant women

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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).

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11140316/

Clinical efficacy of cyclosporin and natamycin for fungal ... Using CYSP and NAT as a combination therapy for fungal keratitis can substantially heighten the therapeutic effects, promote visual acuity recovery, and induce ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06658002?term=NATAMYCIN&viewType=Table&rank=2

Fungal Ulcer Treatment Augmented With Natamycin and ... The primary outcome of this pilot trial is best corrected visual acuity (BCVA) at 3 months. The specific aims of this trial are to: to determine if early use of ...

3. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT06658002

Fungal Ulcer Treatment Augmented With Natamycin and ... 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 ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0021515599002233

Long-Term Effects of Topical Cyclosporine A Treatment ... Rejection occurred after 12 to 24 months in 3 of 9 eyes, but could be resolved by resumption of cyclosporine.127 In another study of cyclosporine 2% as an ...

5. enviromicro-journals.onlinelibrary.wiley.com enviromicro-journals.onlinelibrary.wiley.com/doi/full/10.1111/jam.14126

Antifungal activity of immunosuppressants used alone or in ... Cyclosporine A (CsA), a natural product of soil fungi, exhibited significant synergistic effects with FLC against several fungi, including C.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11458673/

Real-world insights and outcomes related to ciclosporin A 0.1 ... Treatment with CsA 0.1% CE provided long-term improvements over 12 months and was generally well tolerated.

7. djcro.duke.edu djcro.duke.edu/index.php/djcro/article/view/55

Cyclosporine as postoperative immunomodulating agent in ... Outcomes included graft rejection, fungal recurrence, visual acuity, and corneal clarity over six months. Results: Five distinct fungal ...