Fungal Ulcer Treatment Augmented With Natamycin and Cyclosporine A

NCT06658002 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: 24-41971
• Study Type: interventional
• Target: 150
• Locations: 2 countries
• Sites: 2

Brief Summary

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.

Conditions

Fungal Keratitis; Corneal Ulcer

Keywords

Corneal Ulcer; Cyclosporine A; Fungal Keratitis; Fungal Corneal Ulcer

Outcome Measures

Primary Outcomes (1)

• Best Spectacle Corrected Visual Acuity (BSCVA)

  12 weeks

Secondary Outcomes (4)

• Corneal Scar Size

  12 weeks

• Corneal Perforation Rate

  12 weeks

• Corneal Ulcer Re-epithelialization

  12 weeks

• Microbiologic Cure Rate

  12 weeks

Study Arms (3)

Cyclosporine A (CsA) 0.1%

EXPERIMENTAL

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.

Drug: Cyclosporine A

Cyclosporine A (CsA) 2%

EXPERIMENTAL

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.

Drug: Cyclosporine A

Placebo

PLACEBO COMPARATOR

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.

Other: Placebo Comparator: Placebo

Interventions

Cyclosporine A DRUG

Participants with smear or culture proven fungal keratitis are treated for a minimum of 48 hours with topical natamycin and then randomized in a 1:1:1 ratio to receive either topical Cyclosporine A (CsA) 0.1%, 2% or placebo for 4 weeks. Natamycin is continued until the ulcer has healed.

Cyclosporine A (CsA) 0.1%; Cyclosporine A (CsA) 2%

Placebo Comparator: Placebo OTHER

Participants with smear or culture proven fungal keratitis are treated for a minimum of 48 hours with topical natamycin and then randomized in a 1:1:1 ratio to receive either topical Cyclosporine A (CsA) 0.1%, 2% or placebo for 4 weeks. Natamycin is continued until the ulcer has healed.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Smear or culture positive for fungal keratitis, any length.
• Age 18 years.
• Willing to participate in study.

You may not qualify if:

• Co-infection with bacterial or viral keratitis.
• Corneal perforation.
• Requiring therapeutic keratoplasty for fungal keratitis.
• Unwilling or unable to follow up (e.g., living too far from hospital).
• Presenting acuity better than 20/40 = 6/12 = 0.3 Log MAR or worse than 20/400 = 3/60 = +1.3 Log MAR.
• Subjects taking cyclosporine at any concentration on presentation.
• Acuity worse than 20/200 = 6/60 = +1.0 Log MAR in unaffected eye.
• Pregnant women.
• Penetrating Keratoplasty.
• Presents with a 0-7 day history of topical steroid.

Sponsors & Collaborators

• University of California, San Francisco: lead
• Aravind Eye Hospitals, India: collaborator
• Aravind Eye Care System: collaborator

Study Sites (2)

University of California, San Farncisco

San Francisco, California, 94143, United States

NOT YET RECRUITING

Aravind Eye Institute

Pondicherry, Tamil Nadu, 605 007, India

RECRUITING

Related Publications (6)

• Chatterjee S, Agrawal D. Use of Topical Cyclosporine 0.1% in Therapeutic Penetrating Keratoplasty for Fungal Keratitis. Cornea. 2022 Sep 1;41(9):1116-1121. doi: 10.1097/ICO.0000000000002827. Epub 2021 Sep 3.

  PMID: 34483271 BACKGROUND

• Kauss Hornecker M, Charles Weber S, Brandely Piat ML, Darrodes M, Jomaa K, Chast F. [Cyclosporine eye drops: A 4-year retrospective study (2009-2013)]. J Fr Ophtalmol. 2015 Oct;38(8):700-8. doi: 10.1016/j.jfo.2015.02.008. Epub 2015 Sep 11. French.

  PMID: 26371985 BACKGROUND

• Bell NP, Karp CL, Alfonso EC, Schiffman J, Miller D. Effects of methylprednisolone and cyclosporine A on fungal growth in vitro. Cornea. 1999 May;18(3):306-13. doi: 10.1097/00003226-199905000-00012.

  PMID: 10336034 BACKGROUND

• Perry HD, Doshi SJ, Donnenfeld ED, Bai GS. Topical cyclosporin A in the management of therapeutic keratoplasty for mycotic keratitis. Cornea. 2002 Mar;21(2):161-3. doi: 10.1097/00003226-200203000-00006.

  PMID: 11862086 BACKGROUND

• Cordeiro RA, Macedo RB, Teixeira CEC, Marques FJF, Bandeira TJPG, Moreira JLB, Brilhante RSN, Rocha MFG, Sidrim JJC. The calcineurin inhibitor cyclosporin A exhibits synergism with antifungals against Candida parapsilosis species complex. J Med Microbiol. 2014 Jul;63(Pt 7):936-944. doi: 10.1099/jmm.0.073478-0. Epub 2014 Apr 10.

  PMID: 24722799 BACKGROUND

• Survase SA, Kagliwal LD, Annapure US, Singhal RS. Cyclosporin A--a review on fermentative production, downstream processing and pharmacological applications. Biotechnol Adv. 2011 Jul-Aug;29(4):418-35. doi: 10.1016/j.biotechadv.2011.03.004. Epub 2011 Apr 5.

  PMID: 21447377 BACKGROUND

MeSH Terms

Conditions

Corneal Ulcer

Interventions

Cyclosporine

Condition Hierarchy (Ancestors)

Eye Infections; Infections; Keratitis; Corneal Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Gerami D Seitzman, MD

  UCSF Proctor Foundation

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gerami D Seitzman, MD

CONTACT

4154761442; gerami.seitzman@ucsf.edu

Thomas Lietman, MD

CONTACT

tom.lietman@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The treating and examining doctors and all participants will be masked to the identity of the medication in each group. The study drug will be labeled A, B ,C D, E, F with two letters to each treatment group. The only people who will not be masked is the pharmacist at Pondicherry who relabels the medications with the study drug code and maintains the master key of which drug belongs to which study label, the data analyst responsible for generating the randomization code, and a United States study coordinator who is responsible for relabeling protocol and training. The study coordinator at Aravind will not be informed of the master key but will be aware of the study drug allocation name as he/she will be dispensing study drug to the participant. The study coordinator at Aravind will review the drops with the patient each visit. The participants will be informed to not show the examining doctor any of the medications. The study doctors will not ask to see the study medications.
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a randomized controlled trial in which participants with smear or culture proven fungal keratitis are treated for a minimum of 48 hours with topical natamycin and then randomized in a 1:1:1 ratio to receive either topical Cyclosporine A (CsA) 0.1% or CsA 2% or placebo for 4 weeks. In cases of bilateral fungal keratitis, if both eyes fit inclusion criteria, the eye with worse acuity will be randomized. The primary outcome is Best Corrected Visual Acuity (BCVA) at 3 months.

Study Record Dates

• First Submitted: October 23, 2024
• First Posted: October 26, 2024
• Study Start: September 1, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: June 5, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1); US (1)